Gut Dysbiosis Module

Module gut_dysbiosis 2 disorders Pathograph 4

A conserved mechanism module for the hallmark of aging (Lopez-Otin et al., 2023) termed dysbiosis: the age-associated alteration of the gut microbiome and its downstream contribution to systemic aging. With age the composition of the intestinal microbiota drifts - older people show greater inter-individual variation and increasingly individual-unique communities - and this is coupled to increased intestinal permeability. Loss of barrier integrity permits microbial products to translocate, driving age-associated systemic inflammation and macrophage dysfunction; germ-free and cohort studies indicate the microbiota is causally involved in the age-related rise in circulating inflammatory mediators. Gut-microbiome patterns track healthy aging and even predict survival. Dysbiosis is thus an integrative hallmark feeding inflammaging and broader age-related morbidity. Individual disorder entries declare conformance via conforms_to on their pathophysiology nodes, substituting the disease-specific microbiome or barrier context while preserving the conserved microbiota-shift -> barrier-failure -> systemic-inflammation -> age-related-decline chain.

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Pathophysiology Nodes

4 shared nodes are defined in this module.

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Cell Types

No cell types are annotated for this module.

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Biological Processes

Notes

This is a mechanism module, not a specific disease. Disorder entries reference individual nodes via conforms_to (e.g., "gut_dysbiosis#Intestinal Barrier Dysfunction and Microbial Translocation"). Conforming nodes in disorder files should include the corresponding biological processes and causal edges, specialized to their disease context. Dysbiosis is an integrative hallmark that feeds the inflammaging module (systemic inflammation is the shared interface); route the systemic-inflammation consequences there rather than re-deriving them. Key conformance target: "gut_dysbiosis#Intestinal Barrier Dysfunction and Microbial Translocation".

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Used By Disorder Entries

Idiopathic Pulmonary Fibrosis via Gut dysbiosis and microbial metabolite dysregulation → Age-Associated Gut Microbiota Alteration

Parkinson's Disease via Gut Microbiome Dysbiosis → Age-Associated Gut Microbiota Alteration , Intestinal Inflammation and Barrier Dysfunction → Intestinal Barrier Dysfunction and Microbial Translocation

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Pathograph

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Pathophysiology

Age-Associated Gut Microbiota Alteration

trigger

With age the composition of the gut microbiota shifts: older individuals display greater inter-individual variation than younger adults and, from mid-to-late adulthood, increasingly unique individual microbiome compositions. This age-associated compositional drift is the initiating alteration of the hallmark.

Used by disorders

Idiopathic Pulmonary Fibrosis as Gut dysbiosis and microbial metabolite dysregulation

Parkinson's Disease as Gut Microbiome Dysbiosis

Downstream

Intestinal Barrier Dysfunction and Microbial Translocation

Intestinal Barrier Dysfunction and Microbial Translocation

central effector

Age-associated dysbiosis is coupled to loss of intestinal barrier integrity (increased permeability), allowing microbial products to translocate across the gut wall. This barrier failure is the conserved central effector that links a shifted microbiota to systemic consequences.

Used by disorders

Parkinson's Disease as Intestinal Inflammation and Barrier Dysfunction

Downstream

Dysbiosis-Driven Systemic Inflammation

Dysbiosis-Driven Systemic Inflammation

amplifier

Translocating microbial products drive the age-associated increase in circulating inflammatory mediators and macrophage dysfunction. Germ-free studies indicate this age-related inflammation is causally dependent on the microbiota. This node is the amplifying interface at which gut dysbiosis feeds inflammaging.

Inflammatory Response GO:0006954 INCREASED

Downstream

Age-Related Health Decline and Reduced Survival