Salmonella Gastroenteritis

Infectious Disease MONDO:0005950 Pathograph 18 Show in embeddings browser Salmonellosis Gastroenteritis

Salmonella gastroenteritis is acute nontyphoidal Salmonella enteric infection acquired when contaminated food, milk, water, or animal contact delivers Salmonella enterica serovars to the distal ileum and colon. The organism uses M-cell uptake and SPI-1 type III secretion effectors to cross and invade the epithelium, activates caspase-1 and neutrophilic inflammation, exploits the inflamed gut lumen as a tetrathionate-supported respiratory niche, and causes diarrhea, fever, abdominal pain, and occasional bloody diarrhea, with rare bacteremia in susceptible hosts.

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🏷

Classifications

Harrison's Part
GASTROINTESTINAL INFECTIOUS DISEASES
⚙

Pathophysiology

10
Proton Pump Inhibitor Gastric Acid Suppression
Proton-pump inhibitor use suppresses gastric acidity, weakening the stomach barrier that normally kills ingested Salmonella and raising susceptibility to Salmonella gastroenteritis.
Downstream
Foodborne Salmonella Ingestion By reducing the acid barrier, PPI exposure lets a larger fraction of ingested Salmonella survive gastric transit to reach the intestine.
Show evidence (2 references)
PMID:18054750 SUPPORT PRIMARY RESULT Human clinical
"gastric acid suppression induced by PPIs but not H2RAs is associated with an increased risk of Campylobacter and Salmonella GE."
In a population case-control study, Salmonella gastroenteritis showed the same PPI-associated risk signal as the overall bacterial-gastroenteritis cohort.
PMID:21999643 SUPPORT REVIEW SYNTHESIS Human clinical
"Severe hypochlorhydria generated by PPI use leads to bacterial colonisation and increased susceptibility to enteric bacterial infection."
A systematic review supports acid suppression as a plausible susceptibility factor for Salmonella and other enteric bacterial infections.
Foodborne Salmonella Ingestion
Viable nontyphoidal Salmonella organisms are swallowed with contaminated food, water, milk, or material from colonized animals.
Downstream
M-Cell FimH-GP2 Uptake Organisms that survive gastric transit reach Peyer's-patch follicle associated epithelium and can bind GP2 on M cells through type 1 fimbriae.
SPI-1 Type III Secretion and Enterocyte Invasion Luminal Salmonella can directly invade enterocytes after SPI-1 type III secretion system assembly and effector translocation.
Show evidence (1 reference)
PMID:31321641 SUPPORT BACKGROUND Human clinical
"Human infection occurs by fecal-oral transmission through ingestion of contaminated food, milk, or water (inter-human or zoonotic transmission)."
Supports ingestion of contaminated material as the initiating exposure for nontyphoidal Salmonella infection.
M-Cell FimH-GP2 Uptake
Salmonella uses type 1-pilus FimH to bind glycoprotein 2 on intestinal M cells, which can transcytose luminal bacteria into gut lymphoid tissue.
M cell of gut CL:0000682 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves M cell of gut (CL:0000682). CL:0000682 is a cell type from the Cell Ontology.
adhesion of symbiont to host GO:0044406 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves adhesion of symbiont to host (GO:0044406). GO:0044406 is a biological process from the Gene Ontology.
Downstream
Neutrophilic Enterocolitis M-cell uptake moves Salmonella across the epithelium, contributing to mucosal invasion that triggers acute intestinal inflammation.
Show evidence (2 references)
PMID:21468225 SUPPORT BACKGROUND Model organism
"GP2 interacts with FimH, a major component of the type 1 pilus on the outer membrane of a subset of gram-negative enterobacilli such as E. coli and Salmonella enterica."
Identifies the GP2-FimH receptor pair that links Salmonella to intestinal M-cell uptake.
PMID:19828638 SUPPORT PRIMARY RESULT Model organism
"Sections of the intestinal wall taken 2 hours after the introduction of the bacteria revealed substantially enhanced uptake of both Salmonella enterica serovar Typhimurium (35-fold) and Yersinia enterocolitica (46-fold) as a consequence of villous M cell induction by RANKL"
Shows that experimentally expanded M cells take up S. Typhimurium from the gut lumen.
SPI-1 Type III Secretion and Enterocyte Invasion
Salmonella pathogenicity island 1 encodes a type III secretion system that injects Sip and Sop effectors into intestinal epithelial cells, rearranges the actin cytoskeleton, and drives enterocyte invasion.
enterocyte CL:0000584 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves enterocyte (CL:0000584). CL:0000584 is a cell type from the Cell Ontology.
Downstream
SipB Caspase-1 IL-1β Activation SPI-1 translocation delivers SipB, which binds caspase-1 and activates IL-1β processing.
SopB-Dependent Fluid Secretion SPI-1 translocation delivers SopB, which contributes to Salmonella-driven intestinal fluid secretion and inflammation.
Show evidence (2 references)
PMID:41212225 SUPPORT BACKGROUND Model organism
"The Type III secretion system (T3SS) of Salmonella is a syringe-like protein injection apparatus that translocates bacterial effector proteins into host cells and is essential for epithelial invasion and early stages of pathogenesis."
Supports SPI-1 type III secretion as the Salmonella machinery that delivers effectors and initiates epithelial invasion.
PMID:29522566 SUPPORT PRIMARY RESULT Model organism
"Our results demonstrate the critical but redundant role of SopE2 and SipA for enterocyte invasion, prerequisite for transcriptional stimulation and mucosal translocation in vivo."
Defines individual SPI-1 effectors required for Salmonella enterocyte invasion in vivo.
SipB Caspase-1 IL-1β Activation
Translocated Salmonella SipB binds host caspase-1, enabling cleavage and activation of pro-IL-1β as part of the early inflammatory response.
inflammatory response GO:0006954 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves inflammatory response (GO:0006954). GO:0006954 is a biological process from the Gene Ontology.
Downstream
Neutrophilic Enterocolitis IL-1β signaling contributes to neutrophil recruitment into the infected distal bowel.
Show evidence (1 reference)
PMID:11402005 SUPPORT BACKGROUND Model organism
"SipB binds and activates caspase-1, which in turn activates the proinflammatory cytokine interleukin-1beta through cleavage."
Links the Salmonella SipB effector to caspase-1 and inflammatory IL-1β activation.
SopB-Dependent Fluid Secretion
The Salmonella SopB inositol phosphate phosphatase contributes to the intestinal fluid secretion and inflammatory response induced by S. Typhimurium in the ileal mucosa.
Downstream
Neutrophilic Enterocolitis SopB contributes to the inflammatory component of Salmonella enteritis.
Inflammatory-Secretory Diarrhea SopB-linked fluid secretion is one effector-level input into acute Salmonella diarrhea.
Show evidence (1 reference)
PMID:11402005 SUPPORT PRIMARY RESULT Model organism
"The sopB mutant induced the same amount of TUNEL-positive cells as the wild type, but it was attenuated for induction of fluid secretion and inflammation."
Shows SopB contributes to secretory and inflammatory enteritis in a calf ileal-loop Salmonella model.
Neutrophilic Enterocolitis
SPI-1-dependent epithelial invasion and inflammatory signaling recruit neutrophils into the distal ileal and colonic mucosa, producing acute inflammatory enterocolitis.
neutrophil CL:0000775 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves neutrophil (CL:0000775). CL:0000775 is a cell type from the Cell Ontology.
inflammatory response GO:0006954 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves inflammatory response (GO:0006954). GO:0006954 is a biological process from the Gene Ontology.
ileum UBERON:0002116 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in ileum (UBERON:0002116). UBERON:0002116 is an anatomical location from the Uberon multi-species anatomy ontology. colon UBERON:0001155 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in colon (UBERON:0001155). UBERON:0001155 is an anatomical location from the Uberon multi-species anatomy ontology.
Animal models
Streptomycin-Pretreated S. Typhimurium Mouse Colitis Mouse recapitulates The model produces SPI-1-linked luminal neutrophil accumulation in the cecum, matching the acute inflammatory enterocolitis node.
Downstream
Inflammatory-Secretory Diarrhea Neutrophilic mucosal inflammation and SopB-associated secretion generate the watery or inflammatory diarrhea of Salmonella gastroenteritis.
Tetrathionate-Respiring Salmonella Bloom The inflamed gut oxidizes thiosulfate to tetrathionate, creating a respiratory electron acceptor that Salmonella can exploit anaerobically.
Show evidence (1 reference)
PMID:21327114 SUPPORT PRIMARY RESULT Model organism
"Large numbers of luminal neutrophils were observed in the ceca of WT-infected, but not in invAmut or ssaRmut infected mice."
Supports neutrophil recruitment as a SPI-1-linked tissue response in enteric Salmonella infection.
Tetrathionate-Respiring Salmonella Bloom
Reactive chemistry in the inflamed intestine converts host thiosulfate to tetrathionate; S. Typhimurium then uses tetrathionate as an electron acceptor to respire ethanolamine and outgrow fermentative gut microbiota.
Downstream
Inflammatory-Secretory Diarrhea Respiratory growth in the inflamed lumen helps maintain high Salmonella burdens during acute transmissible enterocolitis.
Show evidence (1 reference)
PMID:21969563 SUPPORT PRIMARY RESULT Model organism
"By inducing intestinal inflammation, S. Typhimurium sidesteps nutritional competition and gains the ability to use an abundant simple substrate, ethanolamine, which is provided by the host."
Shows how inflammation supplies Salmonella with a metabolic advantage in the gut lumen.
Inflammatory-Secretory Diarrhea
Combined mucosal exudation and epithelial fluid secretion produce acute diarrhea, abdominal cramping, fever, and sometimes visibly bloody diarrhea.
Downstream
Diarrhea Intestinal fluid secretion and exudation directly produce the high-volume loose stools that define the dominant Salmonella gastroenteritis symptom.
Fever The acute inflammatory enterocolitis syndrome presents with fever in most culture-confirmed pediatric Salmonella gastroenteritis cohorts.
Abdominal Pain Inflamed ileocolonic mucosa and associated motility changes manifest as abdominal cramping and pain during acute Salmonella enterocolitis.
Bloody Diarrhea Mucosal inflammation and exudation sometimes make Salmonella diarrhea visibly bloody.
Nontyphoidal Salmonella Bacteremia In a minority of patients, enteric infection progresses past the gut into bloodstream infection.
Show evidence (1 reference)
PMID:36449648 SUPPORT PRIMARY RESULT Human clinical
"The most common clinical symptoms were diarrhea (n = 166, 96.5%), fever (n = 113, 65.7%) and abdominal pain (n = 73, 42.4%)."
Documents the core symptomatic phenotype produced by acute Salmonella enterocolitis.
Nontyphoidal Salmonella Bacteremia
About five percent of nontyphoidal Salmonella gastroenteritis cases progress to bacteremia, which can seed focal infections such as aortitis, endovascular infection, osteomyelitis, or meningitis.
Show evidence (1 reference)
PMID:31321641 SUPPORT BACKGROUND Human clinical
"Approximately 5% of patients with NTS gastroenteritis develop bacteremia and the incidence of extra-intestinal focal infection in NTS bacteremia is about 40%."
Quantifies the bloodstream and extraintestinal-focal complication branch of nontyphoidal Salmonella gastroenteritis.
⬡

Pathograph

Use Group by to collapse related nodes into one box. Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Salmonella Gastroenteritis Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
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Phenotypes

6
Digestive 3
Diarrhea VERY_FREQUENT HP:0002014 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Diarrhea (HP:0002014). HP:0002014 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:36449648 SUPPORT PRIMARY RESULT Human clinical
"The most common clinical symptoms were diarrhea (n = 166, 96.5%), fever (n = 113, 65.7%) and abdominal pain (n = 73, 42.4%)."
Supports diarrhea as a very frequent symptom in culture-confirmed pediatric Salmonella gastroenteritis.
Vomiting FREQUENT HP:0002013 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Vomiting (HP:0002013). HP:0002013 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:27668899 SUPPORT PRIMARY RESULT Human clinical
"The presenting symptoms were diarrhoea (95.5%), fever (61.1%), vomiting (34.3%), abdominal pain (32.8%), loss of appetite (7.4%) and malaise (7.4%)."
Supports vomiting as a frequent symptom in pediatric non-typhoidal Salmonella gastroenteritis.
Bloody Diarrhea OCCASIONAL HP:0025085 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Bloody diarrhea (HP:0025085). HP:0025085 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:36449648 SUPPORT PRIMARY RESULT Human clinical
"Bloody diarrhea was seen in 19.2% of patients."
Supports visibly bloody diarrhea as an occasional Salmonella gastroenteritis manifestation.
Metabolism 2
Fever FREQUENT HP:0001945 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Fever (HP:0001945). HP:0001945 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:36449648 SUPPORT PRIMARY RESULT Human clinical
"The most common clinical symptoms were diarrhea (n = 166, 96.5%), fever (n = 113, 65.7%) and abdominal pain (n = 73, 42.4%)."
Supports fever as a frequent symptom in Salmonella gastroenteritis.
Dehydration OCCASIONAL HP:0001944 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Dehydration (HP:0001944). HP:0001944 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:27668899 SUPPORT PRIMARY RESULT Human clinical
"Fever and dehydration (moderate and/or severe) were detected in 11 (16.4%) patients."
Supports dehydration as an occasional complication of pediatric non-typhoidal Salmonella gastroenteritis.
Constitutional 1
Abdominal Pain FREQUENT HP:0002027 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Abdominal pain (HP:0002027). HP:0002027 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:36449648 SUPPORT PRIMARY RESULT Human clinical
"The most common clinical symptoms were diarrhea (n = 166, 96.5%), fever (n = 113, 65.7%) and abdominal pain (n = 73, 42.4%)."
Supports abdominal pain as a frequent symptom in Salmonella gastroenteritis.
🧬

Genetic Associations

1
IL12RB1 (Biallelic IL12RB1 loss of function impairs IL-12/IL-23-induced IFN-gamma immunity and increases susceptibility to systemic Salmonella infection.)
Gene: IL12RB1 hgnc:5971 gene page HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is IL12RB1 (hgnc:5971). hgnc:5971 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: SUSCEPTIBILITY
Show evidence (2 references)
PMID:28865061 SUPPORT PRIMARY RESULT Human clinical
"Genetic analysis revealed a bi-allelic mutation in IL12RB1 (C291Y) resulting in complete IL-12Rβ1 deficiency."
Identifies biallelic IL12RB1 mutation as the cause of complete IL-12Rβ1 deficiency in a patient with Salmonella infection.
PMID:29995221 SUPPORT BACKGROUND Human clinical
"About half the IL-12Rβ1-deficient patients also present infectious diseases caused by Salmonella species."
Summarizes prior IL-12Rβ1-deficiency cohorts showing Salmonella infection as a recurrent manifestation of this IFN-gamma-axis susceptibility.
💊

Medical Actions

2
Fluid and Electrolyte Rehydration
Action: Fluid TherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Fluid Therapy (NCIT:C116537). NCIT:C116537 is a clinical intervention from the NCI Thesaurus. NCIT:C116537
Oral rehydration solution, with intravenous fluids when oral replacement is insufficient, restores water and electrolytes lost through Salmonella inflammatory-secretory diarrhea and prevents or corrects dehydration without needing to inhibit the pathogen directly.
Mechanism Target:
RESTORES Dehydration — Fluid and electrolyte replacement corrects the dehydration produced by diarrheal water and salt losses.
Show evidence (1 reference)
PMID:8855579 SUPPORT REVIEW SYNTHESIS Human clinical
"Oral rehydration solution (ORS), the best treatment of dehydration due to acute diarrhea, is the most important medical advance of this century"
Establishes rehydration as the supportive treatment for dehydration from acute diarrhea, the main management target in uncomplicated Salmonella gastroenteritis.
Severe or High-Risk Case Antimicrobial Therapy
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: Ciprofloxacin NCIT:C375 NCI Thesaurus (NCIT) Relation: this treatment uses this therapeutic agent This treatment uses Ciprofloxacin (NCIT:C375). NCIT:C375 is a therapeutic agent from the NCI Thesaurus. Ceftriaxone NCIT:C62020 NCI Thesaurus (NCIT) Relation: this treatment uses this therapeutic agent This treatment uses Ceftriaxone (NCIT:C62020). NCIT:C62020 is a therapeutic agent from the NCI Thesaurus.
Platform: Small molecule
Moderate uncomplicated Salmonella gastroenteritis generally does not require antibiotics, but severe cases and high-risk patients are treated with active agents such as ciprofloxacin or ceftriaxone.
Mechanism Target:
INHIBITS Nontyphoidal Salmonella Bacteremia — Susceptible antibiotics reduce invasive bloodstream and focal nontyphoidal Salmonella burden in severe or high-risk disease.
Show evidence (1 reference)
PMID:19000862 SUPPORT BACKGROUND Human clinical
"There is no argument to treat moderate salmonella gastroenteritis or carriage. However, the severe cases and those occurring in high risk patient must be treated (ciprofloxacin or ceftriaxone)."
Supports reserving ciprofloxacin or ceftriaxone treatment for severe and high-risk Salmonella gastroenteritis rather than routine moderate disease.
🔬

Diagnosis

2
Stool Culture and Multiplex PCR Detection
Stool culture provides a reference diagnostic method for Salmonella gastroenteritis and can be supplemented by multiplex PCR gastrointestinal panels that detect Salmonella DNA even when culture is negative.
Stool Culture
Show evidence (1 reference)
PMID:27668899 SUPPORT PRIMARY RESULT Human clinical
"The definitive diagnosis was made with positive stool culture (n = 65) and/or PCR test (n = 4)."
Documents stool culture and PCR confirmation in a pediatric non-typhoidal Salmonella gastroenteritis cohort.
Blood Culture for Invasive Disease
Blood culture is required to confirm the invasive bacteremic branch because invasive nontyphoidal Salmonella can present nonspecifically with fever.
Microbial Culture Procedure NCIT:C25300 NCI Thesaurus (NCIT)
Show evidence (1 reference)
PMID:30657108 SUPPORT REVIEW SYNTHESIS Other
"the clinical presentation of iNTS disease is often with fever alone, so clinical diagnosis is impossible without blood culture confirmation."
Supports blood culture as the confirmatory diagnostic method when the gastroenteritis course enters the invasive bacteremic branch.
📈

Progression

2
Acute Incubation and Enterocolitis
Age: any age Duration: 6 to 72 hour incubation followed by several days of diarrhea
Show evidence (1 reference)
PMID:8119352 SUPPORT PRIMARY RESULT Human clinical
"As dose increased, median incubation period decreased (37 h in the low exposure group v. 21 h in the medium exposure group v. 17.5 h in the high exposure group, P = 0.006)"
Supports dose-dependent acute incubation timing after Salmonella Enteritidis exposure.
Invasive Extraintestinal Branch
Age: very young, elderly, or immunocompromised hosts
Show evidence (1 reference)
PMID:31321641 SUPPORT BACKGROUND Human clinical
"Approximately 5% of patients with NTS gastroenteritis develop bacteremia and the incidence of extra-intestinal focal infection in NTS bacteremia is about 40%."
Supports bacteremia and focal seeding as a distinct invasive complication branch after enteric nontyphoidal Salmonella infection.
🦠

Infectious Agent

1
Salmonella enterica
Nontyphoidal Salmonella enterica serovars are the foodborne Gram-negative bacteria that cause Salmonella gastroenteritis.
Salmonella enterica NCBITaxon:28901 NCBI Taxonomy (NCBITaxon)
Show evidence (1 reference)
PMID:27668899 SUPPORT PRIMARY RESULT Human clinical
"The main serotypes are Salmonella enteritidis (85%) and Salmonella typhimurium (7.5%)."
Culture-positive pediatric Salmonella gastroenteritis was dominated by nontyphoidal S. enterica serovars Enteritidis and Typhimurium.
↔️

Transmission

1
Fecal-Oral Foodborne Exposure
Humans usually acquire nontyphoidal Salmonella by ingesting contaminated animal-derived foods, contaminated produce, milk, or water, or by oral exposure after contact with colonized animals or people.
Show evidence (1 reference)
PMID:31321641 SUPPORT BACKGROUND Human clinical
"Human infection occurs by fecal-oral transmission through ingestion of contaminated food, milk, or water (inter-human or zoonotic transmission)."
Directly states the fecal-oral, food/milk/water, and zoonotic acquisition routes for nontyphoidal Salmonella.
🐁

Animal Models

1
Streptomycin-Pretreated S. Typhimurium Mouse Colitis
Streptomycin-pretreated mice infected orally with S. Typhimurium model acute cecal and colonic inflammation and defined-microbiota studies test microbiota protection against systemic spread.
Neutrophilic cecal inflammation Salmonella-induced colitis Microbiota-sensitive intestinal inflammation
Species
Mouse
Genotype
Streptomycin-pretreated C57BL/6 mice
Publication
PMID:21327114
Pathograph links
Neutrophilic Enterocolitis recapitulates fidelity: high observes: tissue The model produces SPI-1-linked luminal neutrophil accumulation in the cecum, matching the acute inflammatory enterocolitis node.
Show evidence (1 reference)
PMID:21327114 SUPPORT PRIMARY RESULT Model organism
"Large numbers of luminal neutrophils were observed in the ceca of WT-infected, but not in invAmut or ssaRmut infected mice."
The mouse model recapitulates the neutrophilic luminal response of enteric Salmonella infection.
Show evidence (1 reference)
PMID:26531327 SUPPORT PRIMARY RESULT Model organism
"Infected mice receiving MET-1 lost less weight, had reduced serum cytokines, reduced NF-κB nuclear staining, and decreased neutrophil infiltration in the cecum."
Supports microbiota-sensitive inflammatory Salmonella colitis as a manipulable mouse disease model.
{ }

Source YAML

click to show 
name: Salmonella Gastroenteritis
creation_date: "2026-09-30T10:00:51Z"
description: >-
  Salmonella gastroenteritis is acute nontyphoidal Salmonella enteric infection
  acquired when contaminated food, milk, water, or animal contact delivers
  Salmonella enterica serovars to the distal ileum and colon. The organism uses
  M-cell uptake and SPI-1 type III secretion effectors to cross and invade the
  epithelium, activates caspase-1 and neutrophilic inflammation, exploits the
  inflamed gut lumen as a tetrathionate-supported respiratory niche, and causes
  diarrhea, fever, abdominal pain, and occasional bloody diarrhea, with rare
  bacteremia in susceptible hosts.
category: Infectious Disease
disease_term:
  preferred_term: Salmonella gastroenteritis
  term:
    id: MONDO:0005950
    label: Salmonella gastroenteritis
parents:
- Salmonellosis
- Gastroenteritis
synonyms:
- Nontyphoidal Salmonella gastroenteritis
- Salmonella enterocolitis
- Salmonella food poisoning
references:
- reference: PMID:31321641
  title: Non-typhoidal Salmonella aortitis.
- reference: PMID:36449648
  title: "Salmonella gastroenteritis in children: six-year experience in İstanbul, Turkey."
- reference: PMID:27668899
  title: Report of data on children with non-typhi Salmonella gastroenteritis in a three-year period.
- reference: PMID:18054750
  title: Use of acid-suppressing drugs and the risk of bacterial gastroenteritis.
- reference: PMID:28865061
  title: Severe Enteropathy and Hypogammaglobulinemia Complicating Refractory Mycobacterium tuberculosis Complex Disseminated Disease in a Child with IL-12Rβ1 Deficiency.
- reference: PMID:29995221
  title: A Variety of Alu-Mediated Copy Number Variations Can Underlie IL-12Rβ1 Deficiency.
- reference: PMID:30657108
  title: Invasive Nontyphoidal Salmonella Disease in Africa.
- reference: PMID:21999643
  title: "Systematic review: the use of proton pump inhibitors and increased susceptibility to enteric infection."
- reference: PMID:41212225
  title: Inhibition of the Type III Secretion System of Salmonella Enterica Serovar Typhimurium and Alleviation Pathogenicity Via Treatment with Xanthotoxol.
- reference: PMID:29522566
  title: Minimal SPI1-T3SS effector requirement for Salmonella enterocyte invasion and intracellular proliferation in vivo.
- reference: PMID:21468225
  title: "Glycoprotein 2 (GP2): grabbing the FimH bacteria into M cells for mucosal immunity."
- reference: PMID:19828638
  title: RANKL is necessary and sufficient to initiate development of antigen-sampling M cells in the intestinal epithelium.
- reference: PMID:21327114
  title: Salmonella SPI-1-mediated neutrophil recruitment during enteric colitis is associated with reduction and alteration in intestinal microbiota.
- reference: PMID:11402005
  title: Salmonella-induced cell death is not required for enteritis in calves.
- reference: PMID:21969563
  title: Intestinal inflammation allows Salmonella to use ethanolamine to compete with the microbiota.
- reference: PMID:8119352
  title: Dose-response effects in an outbreak of Salmonella enteritidis.
- reference: PMID:19000862
  title: "[Bacterial diarrheas and antibiotics: European recommendations]."
- reference: PMID:8855579
  title: Oral rehydration therapy.
- reference: PMID:26531327
  title: Administration of defined microbiota is protective in a murine Salmonella infection model.
classifications:
  harrisons_chapter:
  - classification_value: GASTROINTESTINAL
    evidence:
    - reference: PMID:27668899
      reference_title: Report of data on children with non-typhi Salmonella gastroenteritis in a three-year period.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      quote_role: BACKGROUND
      snippet: >-
        The purpose of this study was to evaluate the clinical and laboratory
        data of children with acute gastroenteritis caused by non-typhoid
        Salmonella spp. infections.
      explanation: >-
        Places nontyphoidal Salmonella infection in the acute-gastroenteritis
        clinical category.
  - classification_value: INFECTIOUS_DISEASES
    evidence:
    - reference: PMID:31321641
      reference_title: Non-typhoidal Salmonella aortitis.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      quote_role: BACKGROUND
      snippet: >-
        Human infection occurs by fecal-oral transmission through ingestion of
        contaminated food, milk, or water (inter-human or zoonotic
        transmission).
      explanation: >-
        Identifies nontyphoidal Salmonella disease as a transmissible bacterial
        infection acquired through fecal-oral exposure.
infectious_agent:
- name: Salmonella enterica
  description: >-
    Nontyphoidal Salmonella enterica serovars are the foodborne Gram-negative
    bacteria that cause Salmonella gastroenteritis.
  infectious_agent_term:
    preferred_term: Salmonella enterica
    term:
      id: NCBITaxon:28901
      label: Salmonella enterica
  evidence:
  - reference: PMID:27668899
    reference_title: Report of data on children with non-typhi Salmonella gastroenteritis in a three-year period.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: PRIMARY_RESULT
    snippet: >-
      The main serotypes are Salmonella enteritidis (85%) and Salmonella
      typhimurium (7.5%).
    explanation: >-
      Culture-positive pediatric Salmonella gastroenteritis was dominated by
      nontyphoidal S. enterica serovars Enteritidis and Typhimurium.
agent_life_cycle:
  description: >-
    Nontyphoidal Salmonella enterica circulates through animal reservoirs that
    contaminate eggs, meat, milk, produce, water, and the food-production
    environment; humans are clinical hosts after fecal-oral exposure.
  hosts:
  - preferred_term: Homo sapiens
    role: clinical host
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  - preferred_term: chicken
    role: poultry reservoir and food-source host
    term:
      id: NCBITaxon:9031
      label: Gallus gallus
  - preferred_term: domestic pig
    role: livestock reservoir and food-source host
    term:
      id: NCBITaxon:9825
      label: Sus scrofa domesticus
  - preferred_term: cattle
    role: livestock reservoir and food-source host
    term:
      id: NCBITaxon:9913
      label: Bos taurus
transmission:
- name: Fecal-Oral Foodborne Exposure
  description: >-
    Humans usually acquire nontyphoidal Salmonella by ingesting contaminated
    animal-derived foods, contaminated produce, milk, or water, or by oral
    exposure after contact with colonized animals or people.
  evidence:
  - reference: PMID:31321641
    reference_title: Non-typhoidal Salmonella aortitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: BACKGROUND
    snippet: >-
      Human infection occurs by fecal-oral transmission through ingestion of
      contaminated food, milk, or water (inter-human or zoonotic
      transmission).
    explanation: >-
      Directly states the fecal-oral, food/milk/water, and zoonotic acquisition
      routes for nontyphoidal Salmonella.
pathophysiology:
- name: Proton Pump Inhibitor Gastric Acid Suppression
  role: susceptibility_factor
  biological_scale: ORGANISM
  description: >-
    Proton-pump inhibitor use suppresses gastric acidity, weakening the stomach
    barrier that normally kills ingested Salmonella and raising susceptibility to
    Salmonella gastroenteritis.
  downstream:
  - target: Foodborne Salmonella Ingestion
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: >-
      By reducing the acid barrier, PPI exposure lets a larger fraction of
      ingested Salmonella survive gastric transit to reach the intestine.
  evidence:
  - reference: PMID:18054750
    reference_title: Use of acid-suppressing drugs and the risk of bacterial gastroenteritis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: PRIMARY_RESULT
    snippet: >-
      gastric acid suppression induced by PPIs but not H2RAs is associated with
      an increased risk of Campylobacter and Salmonella GE.
    explanation: >-
      In a population case-control study, Salmonella gastroenteritis showed the
      same PPI-associated risk signal as the overall bacterial-gastroenteritis
      cohort.
  - reference: PMID:21999643
    reference_title: "Systematic review: the use of proton pump inhibitors and increased susceptibility to enteric infection."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Severe hypochlorhydria generated by PPI use leads to bacterial
      colonisation and increased susceptibility to enteric bacterial infection.
    explanation: >-
      A systematic review supports acid suppression as a plausible
      susceptibility factor for Salmonella and other enteric bacterial
      infections.
- name: Foodborne Salmonella Ingestion
  role: trigger
  biological_scale: ORGANISM
  description: >-
    Viable nontyphoidal Salmonella organisms are swallowed with contaminated
    food, water, milk, or material from colonized animals.
  downstream:
  - target: M-Cell FimH-GP2 Uptake
    causal_link_type: DIRECT
    description: >-
      Organisms that survive gastric transit reach Peyer's-patch follicle
      associated epithelium and can bind GP2 on M cells through type 1 fimbriae.
  - target: SPI-1 Type III Secretion and Enterocyte Invasion
    causal_link_type: DIRECT
    description: >-
      Luminal Salmonella can directly invade enterocytes after SPI-1 type III
      secretion system assembly and effector translocation.
  evidence:
  - reference: PMID:31321641
    reference_title: Non-typhoidal Salmonella aortitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: BACKGROUND
    snippet: >-
      Human infection occurs by fecal-oral transmission through ingestion of
      contaminated food, milk, or water (inter-human or zoonotic
      transmission).
    explanation: >-
      Supports ingestion of contaminated material as the initiating exposure for
      nontyphoidal Salmonella infection.
- name: M-Cell FimH-GP2 Uptake
  biological_scale: CELLULAR
  description: >-
    Salmonella uses type 1-pilus FimH to bind glycoprotein 2 on intestinal
    M cells, which can transcytose luminal bacteria into gut lymphoid tissue.
  cell_types:
  - preferred_term: M cell of gut
    term:
      id: CL:0000682
      label: M cell of gut
  biological_processes:
  - preferred_term: adhesion of symbiont to host
    term:
      id: GO:0044406
      label: adhesion of symbiont to host
  downstream:
  - target: Neutrophilic Enterocolitis
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: >-
      M-cell uptake moves Salmonella across the epithelium, contributing to
      mucosal invasion that triggers acute intestinal inflammation.
  evidence:
  - reference: PMID:21468225
    reference_title: "Glycoprotein 2 (GP2): grabbing the FimH bacteria into M cells for mucosal immunity."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    quote_role: BACKGROUND
    snippet: >-
      GP2 interacts with FimH, a major component of the type 1 pilus on the
      outer membrane of a subset of gram-negative enterobacilli such as E. coli
      and Salmonella enterica.
    explanation: >-
      Identifies the GP2-FimH receptor pair that links Salmonella to intestinal
      M-cell uptake.
  - reference: PMID:19828638
    reference_title: RANKL is necessary and sufficient to initiate development of antigen-sampling M cells in the intestinal epithelium.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    quote_role: PRIMARY_RESULT
    snippet: >-
      Sections of the intestinal wall taken 2 hours after the introduction of
      the bacteria revealed substantially enhanced uptake of both Salmonella
      enterica serovar Typhimurium (35-fold) and Yersinia enterocolitica
      (46-fold) as a consequence of villous M cell induction by RANKL
    explanation: >-
      Shows that experimentally expanded M cells take up S. Typhimurium from
      the gut lumen.
- name: SPI-1 Type III Secretion and Enterocyte Invasion
  biological_scale: CELLULAR
  description: >-
    Salmonella pathogenicity island 1 encodes a type III secretion system that
    injects Sip and Sop effectors into intestinal epithelial cells, rearranges
    the actin cytoskeleton, and drives enterocyte invasion.
  cell_types:
  - preferred_term: enterocyte
    term:
      id: CL:0000584
      label: enterocyte
  downstream:
  - target: SipB Caspase-1 IL-1β Activation
    causal_link_type: DIRECT
    description: >-
      SPI-1 translocation delivers SipB, which binds caspase-1 and activates
      IL-1β processing.
  - target: SopB-Dependent Fluid Secretion
    causal_link_type: DIRECT
    description: >-
      SPI-1 translocation delivers SopB, which contributes to Salmonella-driven
      intestinal fluid secretion and inflammation.
  evidence:
  - reference: PMID:41212225
    reference_title: Inhibition of the Type III Secretion System of Salmonella Enterica Serovar Typhimurium and Alleviation Pathogenicity Via Treatment with Xanthotoxol.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    quote_role: BACKGROUND
    snippet: >-
      The Type III secretion system (T3SS) of Salmonella is a syringe-like
      protein injection apparatus that translocates bacterial effector proteins
      into host cells and is essential for epithelial invasion and early stages
      of pathogenesis.
    explanation: >-
      Supports SPI-1 type III secretion as the Salmonella machinery that
      delivers effectors and initiates epithelial invasion.
  - reference: PMID:29522566
    reference_title: Minimal SPI1-T3SS effector requirement for Salmonella enterocyte invasion and intracellular proliferation in vivo.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    quote_role: PRIMARY_RESULT
    snippet: >-
      Our results demonstrate the critical but redundant role of SopE2 and SipA
      for enterocyte invasion, prerequisite for transcriptional stimulation and
      mucosal translocation in vivo.
    explanation: >-
      Defines individual SPI-1 effectors required for Salmonella enterocyte
      invasion in vivo.
- name: SipB Caspase-1 IL-1β Activation
  biological_scale: CELLULAR
  description: >-
    Translocated Salmonella SipB binds host caspase-1, enabling cleavage and
    activation of pro-IL-1β as part of the early inflammatory response.
  biological_processes:
  - preferred_term: inflammatory response
    term:
      id: GO:0006954
      label: inflammatory response
  downstream:
  - target: Neutrophilic Enterocolitis
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: >-
      IL-1β signaling contributes to neutrophil recruitment into the infected
      distal bowel.
  evidence:
  - reference: PMID:11402005
    reference_title: Salmonella-induced cell death is not required for enteritis in calves.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    quote_role: BACKGROUND
    snippet: >-
      SipB binds and activates caspase-1, which in turn activates the
      proinflammatory cytokine interleukin-1beta through cleavage.
    explanation: >-
      Links the Salmonella SipB effector to caspase-1 and inflammatory IL-1β
      activation.
- name: SopB-Dependent Fluid Secretion
  biological_scale: CELLULAR
  description: >-
    The Salmonella SopB inositol phosphate phosphatase contributes to the
    intestinal fluid secretion and inflammatory response induced by
    S. Typhimurium in the ileal mucosa.
  downstream:
  - target: Neutrophilic Enterocolitis
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: >-
      SopB contributes to the inflammatory component of Salmonella enteritis.
  - target: Inflammatory-Secretory Diarrhea
    causal_link_type: DIRECT
    description: >-
      SopB-linked fluid secretion is one effector-level input into acute
      Salmonella diarrhea.
  evidence:
  - reference: PMID:11402005
    reference_title: Salmonella-induced cell death is not required for enteritis in calves.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    quote_role: PRIMARY_RESULT
    snippet: >-
      The sopB mutant induced the same amount of TUNEL-positive cells as the
      wild type, but it was attenuated for induction of fluid secretion and
      inflammation.
    explanation: >-
      Shows SopB contributes to secretory and inflammatory enteritis in a calf
      ileal-loop Salmonella model.
- name: Neutrophilic Enterocolitis
  biological_scale: TISSUE
  description: >-
    SPI-1-dependent epithelial invasion and inflammatory signaling recruit
    neutrophils into the distal ileal and colonic mucosa, producing acute
    inflammatory enterocolitis.
  locations:
  - preferred_term: ileum
    term:
      id: UBERON:0002116
      label: ileum
  - preferred_term: colon
    term:
      id: UBERON:0001155
      label: colon
  cell_types:
  - preferred_term: neutrophil
    term:
      id: CL:0000775
      label: neutrophil
  biological_processes:
  - preferred_term: inflammatory response
    term:
      id: GO:0006954
      label: inflammatory response
  downstream:
  - target: Inflammatory-Secretory Diarrhea
    causal_link_type: DIRECT
    description: >-
      Neutrophilic mucosal inflammation and SopB-associated secretion generate
      the watery or inflammatory diarrhea of Salmonella gastroenteritis.
  - target: Tetrathionate-Respiring Salmonella Bloom
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: >-
      The inflamed gut oxidizes thiosulfate to tetrathionate, creating a
      respiratory electron acceptor that Salmonella can exploit anaerobically.
  evidence:
  - reference: PMID:21327114
    reference_title: Salmonella SPI-1-mediated neutrophil recruitment during enteric colitis is associated with reduction and alteration in intestinal microbiota.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    quote_role: PRIMARY_RESULT
    snippet: >-
      Large numbers of luminal neutrophils were observed in the ceca of
      WT-infected, but not in invAmut or ssaRmut infected mice.
    explanation: >-
      Supports neutrophil recruitment as a SPI-1-linked tissue response in
      enteric Salmonella infection.
- name: Tetrathionate-Respiring Salmonella Bloom
  biological_scale: MOLECULAR
  description: >-
    Reactive chemistry in the inflamed intestine converts host thiosulfate to
    tetrathionate; S. Typhimurium then uses tetrathionate as an electron
    acceptor to respire ethanolamine and outgrow fermentative gut microbiota.
  downstream:
  - target: Inflammatory-Secretory Diarrhea
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: >-
      Respiratory growth in the inflamed lumen helps maintain high Salmonella
      burdens during acute transmissible enterocolitis.
  evidence:
  - reference: PMID:21969563
    reference_title: Intestinal inflammation allows Salmonella to use ethanolamine to compete with the microbiota.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    quote_role: PRIMARY_RESULT
    snippet: >-
      By inducing intestinal inflammation, S. Typhimurium sidesteps nutritional
      competition and gains the ability to use an abundant simple substrate,
      ethanolamine, which is provided by the host.
    explanation: >-
      Shows how inflammation supplies Salmonella with a metabolic advantage in
      the gut lumen.
- name: Inflammatory-Secretory Diarrhea
  biological_scale: ORGANISM
  description: >-
    Combined mucosal exudation and epithelial fluid secretion produce acute
    diarrhea, abdominal cramping, fever, and sometimes visibly bloody diarrhea.
  downstream:
  - target: Diarrhea
    causal_link_type: DIRECT
    description: >-
      Intestinal fluid secretion and exudation directly produce the high-volume
      loose stools that define the dominant Salmonella gastroenteritis symptom.
  - target: Fever
    causal_link_type: DIRECT
    description: >-
      The acute inflammatory enterocolitis syndrome presents with fever in most
      culture-confirmed pediatric Salmonella gastroenteritis cohorts.
  - target: Abdominal Pain
    causal_link_type: DIRECT
    description: >-
      Inflamed ileocolonic mucosa and associated motility changes manifest as
      abdominal cramping and pain during acute Salmonella enterocolitis.
  - target: Bloody Diarrhea
    causal_link_type: DIRECT
    description: >-
      Mucosal inflammation and exudation sometimes make Salmonella diarrhea
      visibly bloody.
  - target: Nontyphoidal Salmonella Bacteremia
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: >-
      In a minority of patients, enteric infection progresses past the gut into
      bloodstream infection.
  evidence:
  - reference: PMID:36449648
    reference_title: "Salmonella gastroenteritis in children: six-year experience in İstanbul, Turkey."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: PRIMARY_RESULT
    snippet: >-
      The most common clinical symptoms were diarrhea (n = 166, 96.5%), fever
      (n = 113, 65.7%) and abdominal pain (n = 73, 42.4%).
    explanation: >-
      Documents the core symptomatic phenotype produced by acute Salmonella
      enterocolitis.
- name: Nontyphoidal Salmonella Bacteremia
  biological_scale: ORGANISM
  description: >-
    About five percent of nontyphoidal Salmonella gastroenteritis cases progress
    to bacteremia, which can seed focal infections such as aortitis,
    endovascular infection, osteomyelitis, or meningitis.
  evidence:
  - reference: PMID:31321641
    reference_title: Non-typhoidal Salmonella aortitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: BACKGROUND
    snippet: >-
      Approximately 5% of patients with NTS gastroenteritis develop bacteremia
      and the incidence of extra-intestinal focal infection in NTS bacteremia is
      about 40%.
    explanation: >-
      Quantifies the bloodstream and extraintestinal-focal complication branch
      of nontyphoidal Salmonella gastroenteritis.
phenotypes:
- name: Diarrhea
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Diarrhea
    term:
      id: HP:0002014
      label: Diarrhea
  evidence:
  - reference: PMID:36449648
    reference_title: "Salmonella gastroenteritis in children: six-year experience in İstanbul, Turkey."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: PRIMARY_RESULT
    snippet: >-
      The most common clinical symptoms were diarrhea (n = 166, 96.5%), fever
      (n = 113, 65.7%) and abdominal pain (n = 73, 42.4%).
    explanation: >-
      Supports diarrhea as a very frequent symptom in culture-confirmed
      pediatric Salmonella gastroenteritis.
- name: Fever
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Fever
    term:
      id: HP:0001945
      label: Fever
  evidence:
  - reference: PMID:36449648
    reference_title: "Salmonella gastroenteritis in children: six-year experience in İstanbul, Turkey."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: PRIMARY_RESULT
    snippet: >-
      The most common clinical symptoms were diarrhea (n = 166, 96.5%), fever
      (n = 113, 65.7%) and abdominal pain (n = 73, 42.4%).
    explanation: >-
      Supports fever as a frequent symptom in Salmonella gastroenteritis.
- name: Abdominal Pain
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Abdominal pain
    term:
      id: HP:0002027
      label: Abdominal pain
  evidence:
  - reference: PMID:36449648
    reference_title: "Salmonella gastroenteritis in children: six-year experience in İstanbul, Turkey."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: PRIMARY_RESULT
    snippet: >-
      The most common clinical symptoms were diarrhea (n = 166, 96.5%), fever
      (n = 113, 65.7%) and abdominal pain (n = 73, 42.4%).
    explanation: >-
      Supports abdominal pain as a frequent symptom in Salmonella
      gastroenteritis.
- name: Vomiting
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Vomiting
    term:
      id: HP:0002013
      label: Vomiting
  evidence:
  - reference: PMID:27668899
    reference_title: Report of data on children with non-typhi Salmonella gastroenteritis in a three-year period.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: PRIMARY_RESULT
    snippet: >-
      The presenting symptoms were diarrhoea (95.5%), fever (61.1%), vomiting
      (34.3%), abdominal pain (32.8%), loss of appetite (7.4%) and malaise
      (7.4%).
    explanation: >-
      Supports vomiting as a frequent symptom in pediatric non-typhoidal
      Salmonella gastroenteritis.
- name: Bloody Diarrhea
  frequency: OCCASIONAL
  phenotype_term:
    preferred_term: Bloody diarrhea
    term:
      id: HP:0025085
      label: Bloody diarrhea
  evidence:
  - reference: PMID:36449648
    reference_title: "Salmonella gastroenteritis in children: six-year experience in İstanbul, Turkey."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: PRIMARY_RESULT
    snippet: Bloody diarrhea was seen in 19.2% of patients.
    explanation: >-
      Supports visibly bloody diarrhea as an occasional Salmonella
      gastroenteritis manifestation.
- name: Dehydration
  frequency: OCCASIONAL
  phenotype_term:
    preferred_term: Dehydration
    term:
      id: HP:0001944
      label: Dehydration
  evidence:
  - reference: PMID:27668899
    reference_title: Report of data on children with non-typhi Salmonella gastroenteritis in a three-year period.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: PRIMARY_RESULT
    snippet: >-
      Fever and dehydration (moderate and/or severe) were detected in 11
      (16.4%) patients.
    explanation: >-
      Supports dehydration as an occasional complication of pediatric
      non-typhoidal Salmonella gastroenteritis.
progression:
- phase: Acute Incubation and Enterocolitis
  age_range: any age
  duration: 6 to 72 hour incubation followed by several days of diarrhea
  evidence:
  - reference: PMID:8119352
    reference_title: Dose-response effects in an outbreak of Salmonella enteritidis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: PRIMARY_RESULT
    snippet: >-
      As dose increased, median incubation period decreased (37 h in the low
      exposure group v. 21 h in the medium exposure group v. 17.5 h in the high
      exposure group, P = 0.006)
    explanation: >-
      Supports dose-dependent acute incubation timing after Salmonella
      Enteritidis exposure.
- phase: Invasive Extraintestinal Branch
  age_range: very young, elderly, or immunocompromised hosts
  evidence:
  - reference: PMID:31321641
    reference_title: Non-typhoidal Salmonella aortitis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: BACKGROUND
    snippet: >-
      Approximately 5% of patients with NTS gastroenteritis develop bacteremia
      and the incidence of extra-intestinal focal infection in NTS bacteremia is
      about 40%.
    explanation: >-
      Supports bacteremia and focal seeding as a distinct invasive complication
      branch after enteric nontyphoidal Salmonella infection.
diagnosis:
- name: Stool Culture and Multiplex PCR Detection
  description: >-
    Stool culture provides a reference diagnostic method for Salmonella
    gastroenteritis and can be supplemented by multiplex PCR gastrointestinal
    panels that detect Salmonella DNA even when culture is negative.
  diagnosis_term:
    preferred_term: Stool Culture
  evidence:
  - reference: PMID:27668899
    reference_title: Report of data on children with non-typhi Salmonella gastroenteritis in a three-year period.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: PRIMARY_RESULT
    snippet: >-
      The definitive diagnosis was made with positive stool culture (n = 65)
      and/or PCR test (n = 4).
    explanation: >-
      Documents stool culture and PCR confirmation in a pediatric non-typhoidal
      Salmonella gastroenteritis cohort.
- name: Blood Culture for Invasive Disease
  description: >-
    Blood culture is required to confirm the invasive bacteremic branch because
    invasive nontyphoidal Salmonella can present nonspecifically with fever.
  diagnosis_term:
    preferred_term: Microbial Culture Procedure
    term:
      id: NCIT:C25300
      label: Microbial Culture Procedure
  evidence:
  - reference: PMID:30657108
    reference_title: Invasive Nontyphoidal Salmonella Disease in Africa.
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      the clinical presentation of iNTS disease is often with fever alone, so
      clinical diagnosis is impossible without blood culture confirmation.
    explanation: >-
      Supports blood culture as the confirmatory diagnostic method when the
      gastroenteritis course enters the invasive bacteremic branch.
genetic:
- name: IL12RB1
  association: >-
    Biallelic IL12RB1 loss of function impairs IL-12/IL-23-induced IFN-gamma
    immunity and increases susceptibility to systemic Salmonella infection.
  relationship_type: SUSCEPTIBILITY
  gene_term:
    preferred_term: IL12RB1
    term:
      id: hgnc:5971
      label: IL12RB1
  evidence:
  - reference: PMID:28865061
    reference_title: Severe Enteropathy and Hypogammaglobulinemia Complicating Refractory Mycobacterium tuberculosis Complex Disseminated Disease in a Child with IL-12Rβ1 Deficiency.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: PRIMARY_RESULT
    snippet: >-
      Genetic analysis revealed a bi-allelic mutation in IL12RB1 (C291Y)
      resulting in complete IL-12Rβ1 deficiency.
    explanation: >-
      Identifies biallelic IL12RB1 mutation as the cause of complete IL-12Rβ1
      deficiency in a patient with Salmonella infection.
  - reference: PMID:29995221
    reference_title: A Variety of Alu-Mediated Copy Number Variations Can Underlie IL-12Rβ1 Deficiency.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: BACKGROUND
    snippet: >-
      About half the IL-12Rβ1-deficient patients also present infectious
      diseases caused by Salmonella species.
    explanation: >-
      Summarizes prior IL-12Rβ1-deficiency cohorts showing Salmonella infection
      as a recurrent manifestation of this IFN-gamma-axis susceptibility.
treatments:
- name: Fluid and Electrolyte Rehydration
  description: >-
    Oral rehydration solution, with intravenous fluids when oral replacement is
    insufficient, restores water and electrolytes lost through Salmonella
    inflammatory-secretory diarrhea and prevents or corrects dehydration without
    needing to inhibit the pathogen directly.
  treatment_term:
    preferred_term: Fluid Therapy
    term:
      id: NCIT:C116537
      label: Fluid Therapy
  target_mechanisms:
  - target: Dehydration
    treatment_effect: RESTORES
    description: >-
      Fluid and electrolyte replacement corrects the dehydration produced by
      diarrheal water and salt losses.
  evidence:
  - reference: PMID:8855579
    reference_title: Oral rehydration therapy.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Oral rehydration solution (ORS), the best treatment of dehydration due to
      acute diarrhea, is the most important medical advance of this century
    explanation: >-
      Establishes rehydration as the supportive treatment for dehydration from
      acute diarrhea, the main management target in uncomplicated Salmonella
      gastroenteritis.
- name: Severe or High-Risk Case Antimicrobial Therapy
  description: >-
    Moderate uncomplicated Salmonella gastroenteritis generally does not require
    antibiotics, but severe cases and high-risk patients are treated with active
    agents such as ciprofloxacin or ceftriaxone.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: Ciprofloxacin
      term:
        id: NCIT:C375
        label: Ciprofloxacin
    - preferred_term: Ceftriaxone
      term:
        id: NCIT:C62020
        label: Ceftriaxone
  target_mechanisms:
  - target: Nontyphoidal Salmonella Bacteremia
    treatment_effect: INHIBITS
    description: >-
      Susceptible antibiotics reduce invasive bloodstream and focal
      nontyphoidal Salmonella burden in severe or high-risk disease.
  evidence:
  - reference: PMID:19000862
    reference_title: "[Bacterial diarrheas and antibiotics: European recommendations]."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: BACKGROUND
    snippet: >-
      There is no argument to treat moderate salmonella gastroenteritis or
      carriage. However, the severe cases and those occurring in high risk
      patient must be treated (ciprofloxacin or ceftriaxone).
    explanation: >-
      Supports reserving ciprofloxacin or ceftriaxone treatment for severe and
      high-risk Salmonella gastroenteritis rather than routine moderate disease.
animal_models:
- name: Streptomycin-Pretreated S. Typhimurium Mouse Colitis
  species: Mouse
  genotype: Streptomycin-pretreated C57BL/6 mice
  publication: PMID:21327114
  description: >-
    Streptomycin-pretreated mice infected orally with S. Typhimurium model acute
    cecal and colonic inflammation and defined-microbiota studies test
    microbiota protection against systemic spread.
  associated_phenotypes:
  - Neutrophilic cecal inflammation
  - Salmonella-induced colitis
  - Microbiota-sensitive intestinal inflammation
  modeled_mechanisms:
  - target: Neutrophilic Enterocolitis
    relationship: RECAPITULATES
    fidelity: HIGH
    model_scale: TISSUE
    description: >-
      The model produces SPI-1-linked luminal neutrophil accumulation in the
      cecum, matching the acute inflammatory enterocolitis node.
    evidence:
    - reference: PMID:21327114
      reference_title: Salmonella SPI-1-mediated neutrophil recruitment during enteric colitis is associated with reduction and alteration in intestinal microbiota.
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      quote_role: PRIMARY_RESULT
      snippet: >-
        Large numbers of luminal neutrophils were observed in the ceca of
        WT-infected, but not in invAmut or ssaRmut infected mice.
      explanation: >-
        The mouse model recapitulates the neutrophilic luminal response of
        enteric Salmonella infection.
  evidence:
  - reference: PMID:26531327
    reference_title: Administration of defined microbiota is protective in a murine Salmonella infection model.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    quote_role: PRIMARY_RESULT
    snippet: >-
      Infected mice receiving MET-1 lost less weight, had reduced serum
      cytokines, reduced NF-κB nuclear staining, and decreased neutrophil
      infiltration in the cecum.
    explanation: >-
      Supports microbiota-sensitive inflammatory Salmonella colitis as a
      manipulable mouse disease model.

review_notes: >-
  This curation uses the acute nontyphoidal gastroenteritis scope and
  deliberately leaves invasive nontyphoidal salmonellosis as a downstream
  complication, not an alternate primary disease class. Deliberately lumped.
  Salmonella enterica serovars Enteritidis, Typhimurium, Dublin, and
  Choleraesuis have different reservoir biases and invasive propensities, but
  acute Salmonella gastroenteritis is represented at the species/syndrome level
  because the MONDO class does not distinguish serovar-specific luminal
  gastroenteritis entities and the core acute intestinal mechanism is shared.
📚

References & Deep Research

References

19
PMID:31321641
Non-typhoidal Salmonella aortitis.
No top-level findings curated for this source.
PMID:36449648
Salmonella gastroenteritis in children: six-year experience in İstanbul, Turkey.
No top-level findings curated for this source.
PMID:27668899
Report of data on children with non-typhi Salmonella gastroenteritis in a three-year period.
No top-level findings curated for this source.
PMID:18054750
Use of acid-suppressing drugs and the risk of bacterial gastroenteritis.
No top-level findings curated for this source.
PMID:28865061
Severe Enteropathy and Hypogammaglobulinemia Complicating Refractory Mycobacterium tuberculosis Complex Disseminated Disease in a Child with IL-12Rβ1 Deficiency.
No top-level findings curated for this source.
PMID:29995221
A Variety of Alu-Mediated Copy Number Variations Can Underlie IL-12Rβ1 Deficiency.
No top-level findings curated for this source.
PMID:30657108
Invasive Nontyphoidal Salmonella Disease in Africa.
No top-level findings curated for this source.
PMID:21999643
Systematic review: the use of proton pump inhibitors and increased susceptibility to enteric infection.
No top-level findings curated for this source.
PMID:41212225
Inhibition of the Type III Secretion System of Salmonella Enterica Serovar Typhimurium and Alleviation Pathogenicity Via Treatment with Xanthotoxol.
No top-level findings curated for this source.
PMID:29522566
Minimal SPI1-T3SS effector requirement for Salmonella enterocyte invasion and intracellular proliferation in vivo.
No top-level findings curated for this source.
PMID:21468225
Glycoprotein 2 (GP2): grabbing the FimH bacteria into M cells for mucosal immunity.
No top-level findings curated for this source.
PMID:19828638
RANKL is necessary and sufficient to initiate development of antigen-sampling M cells in the intestinal epithelium.
No top-level findings curated for this source.
PMID:21327114
Salmonella SPI-1-mediated neutrophil recruitment during enteric colitis is associated with reduction and alteration in intestinal microbiota.
No top-level findings curated for this source.
PMID:11402005
Salmonella-induced cell death is not required for enteritis in calves.
No top-level findings curated for this source.
PMID:21969563
Intestinal inflammation allows Salmonella to use ethanolamine to compete with the microbiota.
No top-level findings curated for this source.
PMID:8119352
Dose-response effects in an outbreak of Salmonella enteritidis.
No top-level findings curated for this source.
PMID:19000862
[Bacterial diarrheas and antibiotics: European recommendations].
No top-level findings curated for this source.
PMID:8855579
Oral rehydration therapy.
No top-level findings curated for this source.
PMID:26531327
Administration of defined microbiota is protective in a murine Salmonella infection model.
No top-level findings curated for this source.

Deep Research

1

Deep research results are used as seeds for research; they do not undergo the same validation as the main records and may contain errors. How we use deep research.

OpenScientist ▸
1. Disease Information
openscientist-autonomous 36 citations 2026-09-30T03:35:55.525051

1. Disease Information

Overview. Salmonella gastroenteritis is an acute inflammatory enterocolitis of the distal small bowel and colon caused by non-typhoidal serovars of the Gram-negative facultative intracellular bacterium Salmonella enterica subsp. enterica. It is the enteric-limited form of non-typhoidal salmonellosis, distinct from enteric (typhoid/paratyphoid) fever caused by the host-restricted serovars Typhi and Paratyphi.

Key identifiers. - MONDO: MONDO:0005950 (Salmonella gastroenteritis / salmonella food poisoning) - MeSH: Salmonella Infections; Salmonella Food Poisoning - ICD-10: A02.0 (Salmonella enteritis); ICD-11: 1A07 (Enteritis due to Salmonella) - SNOMED CT: Salmonella gastroenteritis - NCBI Taxonomy: Salmonella enterica (txid28901); serovar Typhimurium, serovar Enteritidis - OMIM/Orphanet: not a Mendelian disease; no primary OMIM entry (host susceptibility loci discussed in Section 4/9).

Synonyms: non-typhoidal salmonellosis, Salmonella enterocolitis, Salmonella food poisoning, NTS gastroenteritis.

Data source type. The knowledge in this report derives predominantly from aggregated disease-level resources — epidemiological surveillance (GBD, CDC, WHO), clinical cohort studies, systematic reviews, and mechanistic model-organism/in-vitro experiments — rather than from individual EHR-level patient records.

The leading global role of NTS is well documented: "Bacterial pathogens cause approximately 10-15% of episodes, most often Shigella, nontyphoidal Salmonella (NTS) Campylobacter and Shiga toxin-producing Escherichia coli (STEC)" (PMID: 35165210), and "Salmonella enterica serovar Enteritidis (S. Enteritidis) is a commonly reported pathogen which adapts to multiple hosts and causes critical disease burden at a global level" (PMID: 39855357). (Finding F001)

2. Etiology

Primary cause — infectious. The disease is caused by ingestion of viable Salmonella enterica NTS serovars. S. Typhimurium and S. Enteritidis are the most common serovars worldwide.

Environmental / lifestyle risk factors. - Contaminated food and water — poultry, eggs, dairy, beef, and produce are principal vehicles (Section 5, 12). - Gastric acid suppression. Gastric acid is a key host defense barrier. A population case-control study (6,414 cases vs 50,000 controls) found current PPI use raised bacterial gastroenteritis risk RR 2.9 (95% CI 2.5–3.5), rising to RR 5.0 with a doubled PPI dose, while H2-receptor antagonists showed no significant effect: "Current use of PPIs was associated with an increased risk of bacterial GE compared with nonuse, regardless of the treatment duration (RR, 2.9; 95% confidence interval [CI], 2.5-3.5)" (PMID: 18054750). A systematic review confirmed "PPIs appear to increase susceptibility to the following bacterial enteropathogens: Salmonella, Campylobacter jejuni, invasive strains of Escherichia coli" (PMID: 21999643). (Finding F011) - Age extremes (infants, elderly), immunocompromise (HIV), malaria, malnutrition, anemia, sickle cell disease — chiefly risk factors for the invasive branch (Section 8/9).

Host genetic risk factors. Inborn errors of the IL-12/IL-23/IFN-γ axis (Mendelian Susceptibility to Mycobacterial Disease, MSMD; >17 genes) predispose to severe/recurrent NTS. "Mendelian susceptibility to mycobacterial disease is a rare clinical condition... Other infections such as salmonellosis and candidiasis are also reported" (PMID: 28865061); "Autosomal recessive complete IL-12Rβ1 deficiency is the most frequent genetic etiology of MSMD" (PMID: 29995221). Relevant genes: IL12B, IL12RB1, IFNGR1, IFNGR2, STAT1, IL23R. In mouse models, Slc11a1 (NRAMP1) genotype strongly controls Salmonella susceptibility. (Finding F010)

Protective factors. Intact gastric acid barrier; a healthy, competitive gut microbiota (Section 6); defined-microbiota administration is protective in animal models (Section 15).

Gene–environment interaction. Susceptibility emerges from the intersection of host immune-genetic status (IL-12/IFN-γ axis, HIV, hemoglobinopathy) and environmental exposure (ingested dose, acid suppression). This interaction is most consequential for the invasive branch.

3. Phenotypes

The clinical phenotype is well characterized in pediatric cohorts:

Phenotype Frequency HPO term Source
Diarrhea ~95–96% HP:0002014 PMID:36449648, 27668899
Fever ~61–66% HP:0001945 PMID:36449648, 27668899
Abdominal pain ~32–42% HP:0002027 PMID:36449648, 27668899
Vomiting ~34% HP:0002013 PMID:27668899
Bloody diarrhea ~19% HP:0025085 PMID:36449648
Dehydration (moderate/severe) ~16% HP:0001944 PMID:27668899
Loss of appetite ~7% HP:0004396 PMID:27668899
Malaise ~7% HP:0033834 PMID:27668899
Elevated CRP / leukocytosis / elevated ESR common (lab) HP:0011227 / HP:0001974 PMID:27668899

An Istanbul pediatric cohort (n=172) reported: "The most common clinical symptoms were diarrhea (n = 166, 96.5%), fever (n = 113, 65.7%) and abdominal pain (n = 73, 42.4%). Bloody diarrhea was seen in 19.2% of patients" (PMID: 36449648). A second cohort (n=67) corroborated: "The presenting symptoms were diarrhoea (95.5%), fever (61.1%), vomiting (34.3%), abdominal pain (32.8%), loss of appetite (7.4%) and malaise (7.4%)" (PMID: 27668899). (Finding F015)

  • Phenotype type: predominantly symptoms/clinical signs (diarrhea, fever, pain) plus laboratory abnormalities (elevated CRP/ESR, leukocytosis).
  • Age of onset: any age; pediatric predominance in reported cohorts (median age ~59 months).
  • Severity: mild-to-moderate and self-limited in immunocompetent hosts; variable.
  • Progression: acute, episodic, self-limited.
  • Quality of life: transient; acute illness confines patients for days (dose-dependent bed confinement, Section 8), with generally full recovery. Post-infectious reactive arthritis (Section 11) can cause lasting morbidity.

4. Genetic/Molecular Information

Salmonella gastroenteritis is not a Mendelian human genetic disease, so "causal genes," "pathogenic variants," and germline classification per ACMG do not apply in the standard sense. The biologically meaningful genetics fall into two categories:

A. Host susceptibility genes. - IL12B, IL12RB1, IFNGR1, IFNGR2, STAT1, IL23R (MSMD axis) — loss-of-function variants cause severe/disseminated salmonellosis. Documented variants include biallelic IL12RB1 C291Y (absent IFN-γ production) and an IL12B frameshift c.527_528delCT (p.S176Cfs*12) (PMID: 29995221). Functional consequence: loss of IFN-γ–dependent macrophage killing of intracellular Salmonella. (Finding F010) - SLC11A1 (NRAMP1) — divalent-cation transporter at the phagosomal membrane; genotype controls Salmonella susceptibility in mouse models (multiple Ity QTL mapped). - HLA-B27 — a major susceptibility allele for the post-infectious complication reactive arthritis (Section 11). (Finding F004)

B. Bacterial virulence genes (the true "molecular drivers" of disease): - SPI-1 (Salmonella Pathogenicity Island 1) T3SS and effectors SipA, SipB, SipC, SopB, SopE2 — drive epithelial invasion and inflammation. - SPI-2 — intracellular survival/systemic spread. - Regulators hilD, hilC, rtsA, hilA control SPI-1 expression.

No epigenetic host mechanisms, chromosomal abnormalities, or germline/somatic variant frameworks are applicable to this infectious disease.

5. Environmental Information

Infectious agent. Salmonella enterica subsp. enterica, NTS serovars — chiefly Typhimurium and Enteritidis; also S. Choleraesuis (swine-associated, invasive), S. Dublin (cattle-adapted), and reptile-associated serovars (S. Poona, S. Paratyphi B var Java, S. Agbeni, S. Cotham).

Transmission — zoonotic, fecal-oral. "Human infection occurs by fecal-oral transmission through ingestion of contaminated food, milk, or water (inter-human or zoonotic transmission)" (PMID: 31321641). Reptile reservoirs are an increasing source: "Reptile-associated outbreaks of human Salmonella infections are increasing in Canada, coinciding with a rise in the popularity of reptiles as pets" (PMID: 41017027), with documented pet-turtle→child transmission of S. Poona confirmed by identical genomic fragment patterns. (Finding F012)

Lifestyle/environmental factors. Consumption of undercooked poultry/eggs, raw dairy, contaminated produce, and contaminated water; contact with reptiles/amphibians and livestock. Multidrug resistance is rising (e.g., nalidixic acid resistance 97.67% in a Chinese S. Enteritidis collection).

6. Mechanism / Pathophysiology

Ordered causal chain

  1. Ingestion of Salmonella in contaminated food/water → bacteria transit the stomach (gastric acid is a barrier; acid suppression increases risk, F011) → reach the distal ileum, cecum, and colon.
  2. Bacteria access the mucosa via two portals: (a) M cells of the follicle-associated epithelium over Peyer's patches, via the GP2–FimH receptor interaction; and (b) direct invasion of enterocytes via the SPI-1 T3SS. → leads to epithelial entry.
  3. SPI-1 T3SS injects effector proteins (SipA, SopE2, SopB, SipB, SipC) into host cells → results in cytoskeletal rearrangement and bacterial internalization (membrane ruffling/macropinocytosis).
  4. SipB binds and activates caspase-1 → results in cleavage of pro-IL-1β to mature IL-1β (inflammasome activation).
  5. Effector activity + inflammasome → drives massive neutrophil recruitment into the cecal/colonic lumen and lamina propria → acute neutrophilic colitis (SPI-1/invA-dependent).
  6. SopB (inositol phosphatase) activity → causes fluid/electrolyte secretion → secretory-inflammatory diarrhea (cell death itself is not required for enteritis — an inferred but experimentally supported branch point).
  7. Host inflammation → generates reactive oxygen/nitrogen species that oxidize luminal thiosulfate to tetrathionate → enables Salmonella anaerobic respiration of ethanolamine (host-derived) → luminal growth advantage over the fermentative microbiota → sustained bloom and transmission. (Finding F007)
  8. Branch — invasive (iNTS): in immunocompromised/susceptible hosts (HIV, malaria, malnutrition, anemia, sickle cell, IL-12/IFN-γ axis defects), bacteria that survive within macrophages (via SPI-2) → lead to bacteremia (~5% of NTS gastroenteritis) → extraintestinal focal infection (~40% of bacteremias): mycotic aortitis, endovascular infection, osteomyelitis, meningitis. (Findings F008, F013)

Detail

Molecular pathways & effectors (F002). The SPI-1 T3SS is "a syringe-like protein injection apparatus that translocates bacterial effector proteins into host cells and is essential for epithelial invasion and early stages of pathogenesis" (PMID: 41212225). An in-vivo neonatal-mouse study showed "the critical but redundant role of SopE2 and SipA for enterocyte invasion, prerequisite for transcriptional stimulation and mucosal translocation in vivo" (PMID: 29522566). Pharmacologic T3SS inhibition (Xanthotoxol, downregulating hilD/hilC/rtsA/hilA) reduces epithelial invasion without affecting bacterial growth.

Entry portal (F014). M cells are the avid uptake portal: "GP2 interacts with FimH, a major component of the type 1 pilus on the outer membrane of a subset of gram-negative enterobacilli such as E. coli and Salmonella enterica" (PMID: 21468225), and RANKL-driven M-cell differentiation confers "avid uptake of Salmonella and Yersinia organisms" (PMID: 19828638).

Inflammasome & neutrophils (F003). "Large numbers of luminal neutrophils were observed in the ceca of WT-infected, but not in invAmut or ssaRmut infected mice" (PMID: 21327114); "SipB binds and activates caspase-1, which in turn activates the proinflammatory cytokine interleukin-1beta through cleavage" (PMID: 11402005) — and in bovine ileal loops the sopB mutant was attenuated for fluid secretion, showing effectors, not host cell death, drive enteritis.

Metabolic exploitation of inflammation (F007). "By inducing intestinal inflammation, S. Typhimurium sidesteps nutritional competition and gains the ability to use an abundant simple substrate, ethanolamine, which is provided by the host" (PMID: 21969563) — the tetrathionate-respiration mechanism is the mechanistic centerpiece of NTS colonization.

Suggested ontology terms. GO biological processes: GO:0006954 (inflammatory response), GO:0044406 (adhesion to host), GO:0052192 (movement in host), GO:0097202 (activation of cysteine-type endopeptidase/caspase-1), GO:0009410 (response to xenobiotic). Cell types (CL): CL:0000584 (enterocyte), CL:0000682 (M cell of gut), CL:0000775 (neutrophil), CL:0000235 (macrophage). Chemical entities (CHEBI): tetrathionate (CHEBI:48889), ethanolamine (CHEBI:16000).

7. Anatomical Structures Affected

  • Primary organs (Organ level): distal small intestine (ileum, UBERON:0002116), cecum (UBERON:0001153), and colon (UBERON:0001155) — the digestive system.
  • Secondary/complication organs: bloodstream, aorta (mycotic aortitis, UBERON:0000947), bone (osteomyelitis), meninges (meningitis), gallbladder (carriage), pancreas (rare acute pancreatitis) — in invasive disease.
  • Body systems: digestive (primary); cardiovascular, skeletal, and nervous (invasive complications); immune.
  • Tissue level: intestinal epithelium (follicle-associated epithelium and villous enterocytes); lamina propria (neutrophil infiltration).
  • Cell populations: enterocytes (CL:0000584), M cells (CL:0000682), neutrophils (CL:0000775), macrophages (CL:0000235), goblet cells (depleted in colitis).
  • Subcellular compartments (GO CC): Salmonella-containing vacuole (GO:0020005 symbiont-containing vacuole), host plasma membrane (GO:0005886), actin cytoskeleton (GO:0015629), inflammasome (GO:0061702).
  • Localization/lateralization: bilateral/diffuse mucosal involvement of the distal bowel; not lateralized.

8. Temporal Development

Onset. Acute; incubation period ~6–72 hours (median ~12–38 h across outbreaks). Dose-dependent: a classic S. Enteritidis outbreak (n=169) showed "As dose increased, median incubation period decreased (37 h in the low exposure group v. 21 h in the medium exposure group v. 17.5 h in the high exposure group, P = 0.006)" (PMID: 8119352) — with higher doses also producing more vomiting, greater weight loss, more stools, and longer bed confinement. (Finding F018)

Progression & duration. Self-limited; median duration ~1–5 days (typically 2–3): "Median incubation period was 19 h (range: 3-26 h). Median duration of illness was 5 days (range: 1-11 days)" (PMID: 21824356). Convalescent fecal shedding can persist for weeks.

Course pattern. Acute, episodic, self-limited in immunocompetent hosts. Critical window for intervention: early rehydration prevents complications; for invasive disease, early susceptibility-matched antibiotics on day 0–1 improve survival (Section 12).

Chronic branch (model). Chronic murine infection produces persistent intestinal fibrosis (TGF-β1, CTGF, IGF-I upregulation; type I collagen deposition peaking day 21, present to day 70) — an inferred correlate of rare human chronic sequelae (F005).

9. Inheritance and Population

Epidemiology. NTS is a leading foodborne diarrheal pathogen. Global estimates place non-typhoidal salmonellosis at ~90+ million gastroenteritis cases/year. GBD 2021 estimated 509,976 (95%UI 413,361–606,167) incident iNTS cases in 2021: "GBD 2021 estimated 509976...incident cases of iNTS worldwide in 2021, with the most cases and highest age-standardized rate (ASR) in Western Sub-Saharan Africa" (PMID: 40168434). Foodborne bacterial pathogens (incl. NTS) caused "an estimated 364,500 deaths from diarrheal diseases (age-standardized death rate, ASDR 3.63/100,000)" (PMID: 42241982) and 24.6M DALYs in 2021. (Finding F016)

Inheritance. Not applicable — infectious, not heritable. Host susceptibility traits (MSMD axis) follow autosomal-recessive inheritance; HLA-B27 (reactive arthritis) is a co-dominant HLA allele.

Population demographics. - Age distribution: skews to young children; iNTS peaks "early in the second year of life, declining before the age of 3 years" (PMID: 40684736) and in the <1-year group by GBD. Elderly are at high risk of invasive vascular complications. - Sex ratio: slight male predominance in pediatric cohorts (M:F ~55:45). - Geographic distribution: global; invasive burden concentrated in sub-Saharan Africa and South Asia (78.7% of DALYs). S. Typhimurium ST313 drives African epidemics.

10. Diagnostics

Stool culture remains the gold standard, increasingly supplemented by multiplex PCR gastrointestinal panels (BioFire FilmArray GI, QIAstat-Dx), which detect ~23 pathogens in ~80 minutes with markedly higher yield: "QGP demonstrated a higher pathogen detection rate (42.3%; 2,033/4,801) than stool culture (12.6%; 255/2,018) and O&P examination (6.3%; 63/986)" (PMID: 42153668), with >98% negative and near-100% positive agreement. In a Saudi pediatric cohort, Salmonella was the most common pathogen detected (22.1%). (Finding F009)

Test Role Performance / Note
Stool culture Gold standard; enables serotyping & susceptibility Detection ~12.6% yield; slower
Multiplex PCR GI panel Rapid syndromic diagnosis 42.3% yield; ~80 min turnaround
Blood culture Essential for invasive disease iNTS "presentation... is often with fever alone, so clinical diagnosis is impossible without blood culture confirmation" (PMID: 30657108)
Inflammatory markers (CRP, ESR, WBC) Support bacterial etiology Elevated in bacterial AGE
CT angiography / FDG-PET Detect mycotic aneurysm/endovascular focus For complicated bacteremia

Differential diagnosis: other bacterial enteritides (Shigella, Campylobacter, STEC, Yersinia), viral gastroenteritis (rotavirus, norovirus), C. difficile, inflammatory bowel disease. Multiplex panels aid discrimination but require clinical correlation given asymptomatic carriage.

11. Outcome / Prognosis

Immunocompetent hosts. Excellent prognosis; self-limited recovery in 2–7 days, negligible mortality.

Invasive NTS. High morbidity and mortality. A systematic review of Africa (1966–2014) found "NTS have been responsible for up to 39% of community acquired blood stream infections in sub-Saharan Africa with an average CFR of 19%" (PMID: 28056035). In DR Congo children <5, "overall in-hospital case fatality was 25.1% (60/239)" with 60% extensively drug-resistant (PMID: 41429348). (Findings F008, F013)

Complications. - Bacteremia: ~5% of NTS gastroenteritis; ~40% of bacteremias develop extraintestinal focal infection — "Approximately 5% of patients with NTS gastroenteritis develop bacteremia and the incidence of extra-intestinal focal infection in NTS bacteremia is about 40%" (PMID: 31321641). NTS causes ~40% of all infective aortitis; reported fatal cases include ruptured mycotic abdominal aortic aneurysm and aortoesophageal fistula (S. Choleraesuis). (Finding F013) - Reactive arthritis (post-infectious). A major sequela strongly linked to HLA-B27: in a hospitalized cohort (n=63), "HLA-B27 was present in 88%" (PMID: 9370874); in a 592-person outbreak, "HLA-B27 was present more frequently in those who developed Salmonella infection than in healthy controls (OR 3.0)" (PMID: 18528961). HLA-B27+ patients had higher ESR and were the only ones to develop sacroiliitis; 8/50 progressed to chronic spondyloarthropathy at 5–22 yr follow-up. (Finding F004) - Toxic megacolon/intestinal perforation (pediatric, rare).

Prognostic factors: host immune status, age extremes, ingested dose, serovar, antimicrobial susceptibility, presence of endovascular/prosthetic material, severe anemia.

12. Treatment

Core principle. Uncomplicated Salmonella gastroenteritis is managed with rehydration alone; antibiotics are reserved for severe/high-risk cases and invasive disease. European ESPID/ESPGHAN guidance: "There is no argument to treat moderate salmonella gastroenteritis or carriage. However, the severe cases and those occurring in high risk patient must be treated (ciprofloxacin or ceftriaxone)" (PMID: 19000862). Antibiotics do not shorten uncomplicated illness and may prolong carriage. (Finding F017)

Treatment Class / NCIT-type Indication
Oral/IV rehydration & electrolytes Supportive care (NCIT: Fluid Replacement) All patients — mainstay
Ciprofloxacin Fluoroquinolone (NCIT: Ciprofloxacin) Severe/high-risk, invasive
Ceftriaxone / cefotaxime 3rd-gen cephalosporin (NCIT: Ceftriaxone) Severe/invasive, pediatric
Azithromycin Macrolide (NCIT: Azithromycin) Alternative
Subcutaneous IFN-γ Immunomodulator MSMD-associated disseminated salmonellosis

High-risk groups warranting therapy: infants <3 months, elderly, immunocompromised (HIV, MSMD), hemoglobinopathy, and patients with prosthetic/endovascular grafts.

Susceptibility-guided therapy is critical for invasive disease. In DR Congo children, "susceptibility-matched third-generation cephalosporin treatment on hospital day 0-1 had better 14-day in-hospital survival" (PMID: 41429348); with extensive drug resistance in 60% of isolates, empiric mismatches worsen outcomes.

No gene, cell, or RNA-based therapies apply. Surgical intervention (graft excision, aneurysm repair) is required for endovascular complications.

13. Prevention

Primary prevention centers on food and water safety. "Proper food and water treatment, better sanitary facilities, public awareness campaigns, and adherence to food safety laws are all part of prevention measures" (PMID: 38021876). Key measures: safe food handling/cooking (poultry, eggs), pasteurization, hand hygiene, reptile-contact precautions, and One Health surveillance of animal reservoirs and antimicrobial resistance. (Finding F006)

Vaccination. No licensed human NTS vaccine exists. Candidates in preclinical/animal development include: - Live attenuated strains — e.g., ΔmanA ΔsteD (RAST002): "Protective efficacy was assessed through challenge studies, demonstrating up to 80% protection against the homologous strain" (PMID: 41398587) (60–80% heterologous). - Outer-membrane vesicle (OMV) vaccines. - Probiotic-derived antimicrobial peptides.

Prevention levels. Primary — food/water safety, (future) vaccination, gastric-acid preservation (avoid unnecessary PPIs in at-risk patients). Secondary — early rehydration and diagnosis. Tertiary — susceptibility-guided antibiotics and surveillance for endovascular complications in bacteremic patients. Public-health: sanitation, health education, livestock/reptile reservoir control.

14. Other Species / Natural Disease

Salmonella gastroenteritis is fundamentally zoonotic, with broad animal reservoirs.

  • Taxonomy: Salmonella enterica subsp. enterica (NCBI txid59201); serovars Typhimurium, Enteritidis, Dublin, Choleraesuis.
  • Reservoir species: poultry and eggs, cattle, pigs (S. Choleraesuis), and reptiles/amphibians (turtles, snakes, bearded dragons).
  • Natural disease in animals. S. Dublin is a cattle-adapted (host-restricted) serovar causing bovine salmonellosis (systemic disease, abortion, calf enteritis) and serving as a reservoir for human invasive NTS. WGS links human isolates to dairy-cattle isolates and interstate cattle movement (PMID: 42742664; PMID: 42308994). Salmonella is detectable in bovine deep-tissue lymph nodes (~10.8% pooled prevalence) and cow milk (~9.56%), providing zoonotic exposure routes. (Finding F019)
  • Comparative pathology: broad-host-range serovars (Typhimurium, Enteritidis) dominate human sporadic gastroenteritis, whereas host-adapted serovars (Dublin–cattle, Choleraesuis–swine) tend toward invasive disease.
  • Zoonotic transmission: reptile-associated salmonellosis with serovar-specificity (S. Paratyphi B var Java–snakes; S. Agbeni–turtles; S. Cotham/Chester/Tennessee–bearded dragons) is well documented and rising (PMID: 41017027). (Finding F012)

15. Model Organisms

The streptomycin-pretreated mouse colitis model is the principal system recapitulating human Salmonella gastroenteritis. Streptomycin pretreatment of C57BL/6 mice before oral S. Typhimurium produces cecal/colonic colonization with acute neutrophilic mucosal inflammation, edema, epithelial damage, and goblet-cell depletion. (Finding F005)

  • MyD88 (TLR adaptor) is required for full mucosal inflammation and drives fibrosis: "they were impaired in the development of mucosal inflammation" (PMID: 22679002).
  • Chronic model: "Infection led to chronic Salmonella colonization of the cecum and colon followed by edema, mucosal ulcerations, and severe transmural inflammation" (PMID: 18325390), with persistent fibrosis.
  • Microbiota protection: defined microbiota MET-1 protects — "Infected mice receiving MET-1 lost less weight, had reduced serum cytokines, reduced NF-κB nuclear staining, and decreased neutrophil infiltration in the cecum" (PMID: 26531327) — by preserving tight junctions and reducing systemic translocation without lowering intestinal CFU.

Other systems: neonatal mouse (enterocyte invasion, F002); bovine ileal loop (fluid secretion, effector dependence, F003); calf enteritis (S. Dublin); in-vitro Caco-2/Raji M-cell co-culture (M-cell translocation, F014); HeLa/epithelial invasion assays.

Model types: mammalian (mouse, calf), cellular/in-vitro (Caco-2/Raji, HeLa). Genetic models: MyD88−/−, Slc11a1 (Nramp1) congenic strains, IL-12/IFN-γ axis knockouts.

Phenotype recapitulation. The streptomycin mouse reproduces neutrophilic colitis, microbiota disruption, tetrathionate-driven blooming, and (chronically) fibrosis. Limitations: requires antibiotic pretreatment (mice are naturally colitis-resistant); the streptomycin model mimics human enterocolitis but not the human-restricted typhoid syndrome; does not fully capture human iNTS host-genetic diversity.

Mechanistic Model / Interpretation

 INGESTION (contaminated food/water) ── gastric acid barrier (down by PPIs, F011)
|
v
 DISTAL ILEUM / CECUM / COLON
|
   +----+-----------------------------+
   v                                  v
 M CELLS (GP2-FimH, F014)     ENTEROCYTES (SPI-1 T3SS: SipA/SopE2/SopB, F002)
   |                                  |
   +----------------+-----------------+
    v
SipB -> caspase-1 -> IL-1beta (inflammasome, F003)
    v
NEUTROPHIL COLITIS + SopB-driven fluid secretion (F003)
    v
INFLAMMATION oxidizes thiosulfate -> TETRATHIONATE
    v
Salmonella respires ETHANOLAMINE -> LUMINAL BLOOM (F007)
    v
INFLAMMATORY-SECRETORY DIARRHEA (self-limited, 2-7 d, F015/F018)
    |
    v (susceptible host: HIV/malaria/malnutrition/anemia/SCD/IL-12-IFNg, F008/F010)
MACROPHAGE SURVIVAL (SPI-2) -> BACTEREMIA (~5%)
    v
FOCAL INFECTION (~40%): mycotic aortitis, osteomyelitis, meningitis (F013)
    |
    v (post-infectious, HLA-B27, F004)
REACTIVE ARTHRITIS / spondyloarthropathy

The central, distinguishing insight is that Salmonella weaponizes host inflammation: rather than a bystander, inflammation supplies a unique anaerobic electron acceptor (tetrathionate) and nutrient (ethanolamine) that the pathogen alone can exploit, converting the host defense into a competitive advantage. This "inflammation-as-nutrient-niche" paradigm unifies the invasion (SPI-1), inflammasome, and microbiota-bloom findings into a single coherent narrative and explains why the disease is simultaneously inflammatory and self-limited in immunocompetent hosts, while diverging into a lethal invasive branch when macrophage-based control (IFN-γ axis) fails.

Evidence Base

PMID Contribution Finding
35165210 NTS a leading bacterial diarrheal cause F001
39855357 S. Enteritidis global burden, MDR F001
41212225 SPI-1 T3SS essential for invasion F002
29522566 SopE2/SipA redundant for enterocyte invasion F002
21327114 SPI-1-dependent neutrophil recruitment F003
11402005 SipB-caspase-1-IL-1beta; SopB fluid secretion F003
9370874 HLA-B27 88% in reactive salmonella arthritis F004
18528961 HLA-B27 OR 3.0 for Salmonella infection F004
22679002 MyD88 required for mucosal inflammation F005
18325390 Chronic mouse colitis/fibrosis model F005
26531327 Defined microbiota protection F005
41398587 Live attenuated NTS vaccine 80% efficacy F006
38021876 Prevention: food/water safety F006
21969563 Tetrathionate/ethanolamine bloom F007
28056035 iNTS 39% of BSI, CFR 19% in Africa F008
30657108 iNTS host risk factors; blood culture F008/F009
40684736 iNTS age distribution F008
42153668 Multiplex PCR yield 42.3% vs culture F009
28865061 MSMD-salmonellosis link F010
29995221 IL12RB1 leading MSMD defect F010
18054750 PPI RR 2.9 for bacterial GE F011
21999643 PPIs increase Salmonella susceptibility F011
31321641 Fecal-oral zoonotic transmission; 5% bacteremia F012/F013
41017027 Reptile reservoirs, serovar-specific F012
41429348 iNTS 25.1% CFR; susceptibility-matched Rx F013/F017
21468225 GP2-FimH M-cell uptake F014
19828638 RANKL/M-cell avid uptake F014
36449648 Symptom frequencies (n=172) F015
27668899 Symptom frequencies (n=67) F015
40168434 GBD 2021 iNTS 509,976 cases F016
42241982 Foodborne bacterial mortality burden F016
19000862 Antibiotics reserved for severe/high-risk F017
8119352 Dose-dependent incubation/severity F018
21824356 Incubation ~19h, illness self-limited F018
42742664 S. Dublin human-cattle WGS link F019

Limitations and Knowledge Gaps

  1. Template–disease mismatch. The disease-characterization template is designed for Mendelian genetic disorders. Sections on causal genes, pathogenic variant classification (ACMG/AMP), inheritance patterns, penetrance, and germline/somatic origin are not applicable to an infectious disease and were reframed around host susceptibility and bacterial virulence genetics.
  2. Mechanistic evidence is largely from model organisms. The SPI-1 invasion, inflammasome, tetrathionate-bloom, and M-cell findings derive chiefly from mouse, calf, and in-vitro models; direct human intestinal mechanistic validation is limited.
  3. Symptom-frequency data come predominantly from pediatric cohorts (Istanbul, Turkey), which may not generalize to adults or to different serovar distributions.
  4. iNTS burden and CFR rely on regional African surveillance with heterogeneous diagnostics; global iNTS estimates carry wide uncertainty intervals.
  5. No licensed human vaccine; efficacy data are preclinical/murine.
  6. Quality-of-life and long-term functional outcome data (per-phenotype) are sparse for the acute self-limited illness; better characterized only for reactive arthritis sequelae.
  7. Antimicrobial resistance dynamics (e.g., ST313, 3rd-gen cephalosporin resistance) are evolving rapidly and region-specific.

Proposed Follow-up Experiments / Actions

  1. Human mucosal validation of the tetrathionate/ethanolamine niche using ex-vivo human intestinal organoids or biopsy-derived enteroids challenged with S. Typhimurium, measuring luminal tetrathionate and ethanolamine-utilization genes.
  2. Prospective adult and mixed-serovar cohorts to refine symptom frequencies, complication rates, and quality-of-life metrics beyond pediatric data.
  3. Advance NTS vaccine candidates (RAST002 live-attenuated, OMV) into early-phase human trials, prioritizing sub-Saharan African pediatric populations at highest iNTS risk.
  4. Host-genetic screening study correlating IL-12/IFN-γ axis variants (IL12RB1, IL12B, IFNGR1/2, STAT1) and SLC11A1 genotypes with invasive-disease risk in prospective iNTS cohorts.
  5. Antimicrobial stewardship & resistance surveillance integrated with multiplex-PCR diagnostics to guide susceptibility-matched therapy and track ST313 spread.
  6. One Health interventions targeting the S. Dublin cattle-movement transmission network and reptile reservoirs, using WGS-based source attribution.
  7. Therapeutics targeting the inflammation-niche axis (e.g., tetrathionate-pathway or SPI-1 T3SS inhibitors such as Xanthotoxol) as anti-virulence adjuncts that reduce microbiota disruption.

Report compiled from 19 confirmed findings across 5 investigation iterations and 94 reviewed papers. Evidence source types span human clinical cohorts/surveillance, model-organism (mouse, calf) experiments, and in-vitro cellular studies, as annotated throughout.

Artifacts

Reference Validation

Checked with linkml-reference-validator 0.3.0rc3.

Outcome Count
References checked 36
Resolved 36
Unresolved (possible confabulation) 0
Unverifiable 0
References weighed for topical relevance 36
On topic 23
Off topic 0

All extracted references resolved successfully.

Term Validation

Checked with linkml-term-validator 0.4.5, through the ols: adapter.

Outcome Count
Terms checked 30
Resolved 28
Unresolved (possible confabulation) 0
Obsolete 2
Unverifiable 0
Terms whose name was checked 12
Terms named correctly 6
Terms named as a different term 1
Terms whose name is worth a second look 5

Terms the report names something else

These identifiers resolve, so nothing about them looks wrong, and the ontology calls them something unrelated to what the report calls them. That usually means the identifier is not the one the sentence needs:

  • GO:0052192 (1 mention) - the report calls it "movement in host"; GO calls it obsolete movement in environment of other organism involved in symbiotic interaction

Obsolete terms

These terms are real but deprecated. Citing one is not a fabrication; it does mean the report is naming something the ontology has retired:

  • GO:0052192 (obsolete movement in environment of other organism involved in symbiotic interaction) (1 mention)
  • GO:0097202 (obsolete activation of cysteine-type endopeptidase activity) (1 mention)

Terms whose name is worth a second look

The report's name for these is recognisably related to the term's own name without being one of them. A loose paraphrase reads the same way as a citation of the wrong sibling term - and so does a related synonym, which the ontology records precisely because it names something adjacent rather than the same thing - so these are listed rather than judged:

  • MONDO:0005950 (2 mentions) - the report calls it "Salmonella gastroenteritis / salmonella food poisoning"; MONDO calls it Salmonella gastroenteritis
  • GO:0044406 (1 mention) - the report calls it "adhesion to host"; GO calls it adhesion of symbiont to host, and lists "adhesion to host" among its other names
  • GO:0097202 (1 mention) - the report calls it "activation of cysteine-type endopeptidase/caspase-1"; GO calls it obsolete activation of cysteine-type endopeptidase activity
  • GO:0009410 (1 mention) - the report calls it "response to xenobiotic"; GO calls it response to xenobiotic stimulus
  • CL:0000584 (2 mentions) - the report calls it "enterocyte", "Cell populations: enterocytes"; CL calls it enterocyte**, and lists "mature enterocyte" among its other names

Terms named inconsistently

The report gives these identifiers more than one name of its own:

  • CL:0000584 - called "enterocyte", "Cell populations:** enterocytes"