# Gut Microbiota and Obsessive–Compulsive Disorder: A Systematic Review of Mechanistic Links, Evidence from Human and Preclinical Studies, and Therapeutic Prospects

## TL;DR

This paper reviews evidence linking gut microbiota to obsessive-compulsive disorder, suggesting the microbiota may be a modifiable factor in some cases.

## Contribution

The study systematically maps gut-brain mechanisms in OCD and identifies microbiota as a potential modifiable co-factor.

## Key findings

- Human studies show functional patterns like reduced short-chain fatty acids and inflammation linked to OCD severity.
- Transferring OCD patient microbiota to mice induced OCD-like behaviors and neuroinflammation.
- Diet and psychotropic drugs are major sources of heterogeneity in microbiota studies of OCD.

## Abstract

Obsessive–compulsive disorder (OCD) is a multifactorial condition, and interest in gut–brain interactions is increasing. We conducted a systematic two-step review, registered in PROSPERO (CRD420251083936). Step 1 mapped core OCD biology to gut-relevant pathways, including neuroimmune activation, epithelial barrier function, microbial metabolites, and stress circuitry, to clarify plausible mechanisms. Step 2 synthesized evidence from human and preclinical studies that measured or manipulated microbiota. Searches across PubMed, EMBASE, Web of Science, PsycINFO, and Cochrane (September 2025) yielded 357 biological and 20 microbiota-focused studies. Risk of bias was assessed using the Joanna Briggs Institute checklist for human studies and SYRCLE’s tool for animal studies. Although taxonomic findings in human cohorts were heterogeneous, functional patterns converged: reduced short-chain fatty acid capacity, enrichment of pro-inflammatory pathways, and host markers of barrier disruption and inflammation correlating with OCD severity. Transferring patient microbiota to mice induced OCD-like behaviors with neuroinflammatory changes, partly rescued by metabolites or barrier-supporting strains. Mendelian randomization suggested possible causal contributions at higher taxonomic levels. Diet, especially fiber intake, and psychotropic exposure were major sources of heterogeneity. Evidence supports the microbiota as a modifiable co-factor in a subset of OCD, motivating diet-controlled, stratified clinical trials with composite host–microbe endpoints.