graph LR
Depletion_of_Mucosal_Symbiont_Akkermansia_muciniphila["Depletion of Mucosal Symbiont Akkermansia muciniphila"]
GLP_1_Receptor_Agonists["GLP-1 Receptor Agonists"]
Efficient_Intestinal_Energy_Harvest["Efficient Intestinal Energy Harvest"]
Hypothalamic_Dysregulation["Hypothalamic Dysregulation"]
Chronic_Low_Grade_Inflammation["Chronic Low-Grade Inflammation"]
GLP_1_GIP_Dual_Agonists["GLP-1/GIP Dual Agonists"]
Pasteurized_Akkermansia_muciniphila_MucT_Supplementation["Pasteurized Akkermansia muciniphila MucT Supplementation"]
High_Calorie_Diet["High-Calorie Diet"]
Naltrexone_Bupropion["Naltrexone-Bupropion"]
Post_Weight_Loss_Weight_Regain["Post-Weight-Loss Weight Regain"]
Lifestyle_Modification["Lifestyle Modification"]
Intestinal_Barrier_Dysfunction_and_Metabolic_Endotoxemia["Intestinal Barrier Dysfunction and Metabolic Endotoxemia"]
Bariatric_Surgery["Bariatric Surgery"]
Energy_Imbalance["Energy Imbalance"]
Obesogenic_Environment["Obesogenic Environment"]
Increased_Body_Mass_Index["Increased Body Mass Index"]
Orlistat["Orlistat"]
Depletion_of_Mucosal_Symbiont_Akkermansia_muciniphila --> Intestinal_Barrier_Dysfunction_and_Metabolic_Endotoxemia
Intestinal_Barrier_Dysfunction_and_Metabolic_Endotoxemia --> Chronic_Low_Grade_Inflammation
Efficient_Intestinal_Energy_Harvest --> Energy_Imbalance
Post_Weight_Loss_Weight_Regain --> Increased_Body_Mass_Index
High_Calorie_Diet --> Energy_Imbalance
Obesogenic_Environment --> Increased_Body_Mass_Index
Lifestyle_Modification --> Energy_Imbalance
GLP_1_Receptor_Agonists --> Hypothalamic_Dysregulation
GLP_1_Receptor_Agonists --> Energy_Imbalance
GLP_1_Receptor_Agonists --> Post_Weight_Loss_Weight_Regain
GLP_1_GIP_Dual_Agonists --> Energy_Imbalance
GLP_1_GIP_Dual_Agonists --> Post_Weight_Loss_Weight_Regain
Bariatric_Surgery --> Hypothalamic_Dysregulation
Bariatric_Surgery --> Energy_Imbalance
Orlistat --> Efficient_Intestinal_Energy_Harvest
Orlistat --> Post_Weight_Loss_Weight_Regain
Naltrexone_Bupropion --> Hypothalamic_Dysregulation
Pasteurized_Akkermansia_muciniphila_MucT_Supplementation --> Post_Weight_Loss_Weight_Regain
Pasteurized_Akkermansia_muciniphila_MucT_Supplementation --> Efficient_Intestinal_Energy_Harvest
Pasteurized_Akkermansia_muciniphila_MucT_Supplementation --> Intestinal_Barrier_Dysfunction_and_Metabolic_Endotoxemia
style Depletion_of_Mucosal_Symbiont_Akkermansia_muciniphila fill:#dbeafe
style GLP_1_Receptor_Agonists fill:#fce7f3
style Efficient_Intestinal_Energy_Harvest fill:#dbeafe
style Hypothalamic_Dysregulation fill:#dbeafe
style Chronic_Low_Grade_Inflammation fill:#dbeafe
style GLP_1_GIP_Dual_Agonists fill:#fce7f3
style Pasteurized_Akkermansia_muciniphila_MucT_Supplementation fill:#fce7f3
style High_Calorie_Diet fill:#dcfce7
style Naltrexone_Bupropion fill:#fce7f3
style Post_Weight_Loss_Weight_Regain fill:#dbeafe
style Lifestyle_Modification fill:#fce7f3
style Intestinal_Barrier_Dysfunction_and_Metabolic_Endotoxemia fill:#dbeafe
style Bariatric_Surgery fill:#fce7f3
style Energy_Imbalance fill:#dbeafe
style Obesogenic_Environment fill:#dcfce7
style Increased_Body_Mass_Index fill:#fef3c7
style Orlistat fill:#fce7f3
graph LR
Esophageal_Mucosal_Injury["Esophageal Mucosal Injury"]
Na+K+_ATPase_Beta1_Gene_Therapy["Na+,K+-ATPase Beta1 Gene Therapy"]
Alcohol_Consumption["Alcohol Consumption"]
Tight_Junction_Protein_Loss["Tight Junction Protein Loss"]
Dietary_Factors["Dietary Factors"]
Lower_Esophageal_Sphincter_Dysfunction["Lower Esophageal Sphincter Dysfunction"]
Dilated_Intercellular_Spaces["Dilated Intercellular Spaces"]
Tight_Junction_Protein_Loss --> Dilated_Intercellular_Spaces
Dilated_Intercellular_Spaces --> Esophageal_Mucosal_Injury
Alcohol_Consumption --> Lower_Esophageal_Sphincter_Dysfunction
Dietary_Factors --> Lower_Esophageal_Sphincter_Dysfunction
Na+K+_ATPase_Beta1_Gene_Therapy --> Tight_Junction_Protein_Loss
style Esophageal_Mucosal_Injury fill:#dbeafe
style Na+K+_ATPase_Beta1_Gene_Therapy fill:#fce7f3
style Alcohol_Consumption fill:#dcfce7
style Tight_Junction_Protein_Loss fill:#dbeafe
style Dietary_Factors fill:#dcfce7
style Lower_Esophageal_Sphincter_Dysfunction fill:#dbeafe
style Dilated_Intercellular_Spaces fill:#dbeafe
name: com_Obesity__Gastroesophageal_Reflux_Disease
creation_date: "2026-08-19T00:00:00Z"
curation_status: CANDIDATE
notes: >-
Split out of `kb/disorders/Gastroesophageal_Reflux_Disease.yaml`'s
`environmental:` block (dismech#8551): that entry listed `Obesity` as an
"exposure" acting on gastroesophageal reflux disease (GERD), but obesity is
a first-class `Disease` entry in its own right (`kb/disorders/Obesity.yaml`),
a body state rather than something external to the organism the patient is
exposed to. Modeling the relationship as a disease-disease comorbidity
avoids a near-tautological "exposure" edge that ECTO/XCO can never bind a
term for. Directionality is A_BEFORE_B: obesity is conventionally modeled as
an antecedent, modifiable risk state for GERD (raised intra-abdominal
pressure promoting reflux). The `Hiatal Hernia` entry in the same
`environmental:` block is left untouched, since no `kb/disorders/` entry for
hiatal hernia yet exists to migrate it to. Evidence is carried over unchanged
from the original `environmental:` entry rather than dropped.
disease_a:
slug: Obesity
preferred_term: obesity disorder
term:
id: MONDO:0011122
label: obesity disorder
disease_b:
slug: Gastroesophageal_Reflux_Disease
preferred_term: gastroesophageal reflux disease
term:
id: MONDO:0007186
label: gastroesophageal reflux disease
directionality: A_BEFORE_B
effect_direction: RISK
hypotheses:
- description: >-
Increasing body mass index raises intra-abdominal and intragastric
pressure and promotes hiatal hernia formation, mechanically favoring
gastroesophageal reflux; obesity is a major modifiable risk state for
GERD.
evidence:
- reference: PMID:16952280
reference_title: "Body mass index and gastroesophageal reflux disease: a systematic review and meta-analysis"
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "demonstrates a positive association between increasing BMI and the presence of GERD"
explanation: >-
Meta-analysis of 20 studies. The association held within US studies
after stratification by country, while European studies were
heterogeneous. Carried over from the original
`Gastroesophageal_Reflux_Disease.yaml` `environmental:` entry, in the
post-dismech#10003 form that entry now carries on `main`.
association_signals:
- source: LITERATURE
method: LITERATURE_ASSOCIATION
population: >-
Meta-analysis of 20 studies comprising 18,346 patients with GERD; the
quantified estimate is the United States stratum, where the association was
homogeneous. The European stratum was heterogeneous despite stratification
and is deliberately not carried as a metric.
directionality: A_BEFORE_B
effect_direction: RISK
statistics:
metrics:
- metric_type: OR
metric_value: 2.15
metric_ci_lower: 1.89
metric_ci_upper: 2.45
notes: >-
Odds of GERD in obese versus normal-BMI subjects in the US stratum. The
overweight stratum of the same analysis gives OR 1.57 (1.36-1.80), so
the two are ordered by BMI category as a dose-response would predict.
evidence:
- reference: PMID:16952280
reference_title: "Body mass index and gastroesophageal reflux disease: a systematic review and meta-analysis"
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "1.36-1.80, overweight, OR = 1.57, P value homogeneity = 0.51, 95% CI = 1.89-2.45, obese, OR = 2.15"
explanation: >-
Carries both BMI strata of the US estimate. The quote starts mid-clause
because the abstract prints each confidence interval before its point
estimate inside a bracketed span; the obese-stratum OR 2.15 (1.89-2.45)
is the value recorded in the metric above.
- reference: PMID:16952280
reference_title: "Body mass index and gastroesophageal reflux disease: a systematic review and meta-analysis"
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "We identified 20 studies that included 18,346 patients with GERD."
explanation: >-
Establishes the pooled sample behind the effect estimate recorded here.
- reference: PMID:16952280
reference_title: "Body mass index and gastroesophageal reflux disease: a systematic review and meta-analysis"
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Studies from Europe provided heterogeneous results despite stratification for several factors"
explanation: >-
The reason this metric is scoped to the US stratum rather than reported
as a single pooled figure.