Therapeutic modulation of the gut-brain axis in alcohol use disorder: a systematic review
Gut-brain axis interventions (FMT, probiotics, prebiotics, GLP-1 agonists) show a favorable direction in behavioral and physiological outcomes of AUD, but evidence is insufficient to support clinical recommendations due to small samples and statistical inconsistency.
| Population | Adults diagnosed with alcohol use disorder (AUD), including a subgroup with alcohol-associated liver disease (ALD) |
|---|---|
| Intervention | Fecal microbiota transplant (FMT), prebiotics (inulin), probiotics, GLP-1 receptor agonists, and ghrelin receptor antagonists |
| Comparator | Placebo or active control (variable across included studies) |
| Outcome | — |
Context
AUD affects over 280 million people globally, and available pharmacotherapies show modest efficacy with relapse rates exceeding 60%. Gut dysbiosis is a consistent finding in AUD patients and represents a mechanistically plausible target. This systematic review synthesizes the first clinical trials testing this approach.
What the study showed
Of 11 included studies, five documented gut dysbiosis at baseline in AUD patients. Microbiota-directed interventions were associated with benefits in behavioral (craving, consumption, relapse), psychological (anxiety, sociability), and physiological (MELD, AST/ALT, inflammation) outcomes. Of five GLP-1 receptor agonist trials, three demonstrated statistically significant reductions in alcohol use; two were directionally consistent but did not reach significance. Ghrelin receptor antagonism did not alter systemic inflammation in the presence of alcohol. Absolute numbers, 95% CIs, and individual effect sizes were not consolidated by the review.
How it was done
Systematic review of clinical trials identified via PubMed, Google Scholar, Scopus, and ClinicalTrials.gov through 07/31/2026. Eleven studies were included, covering FMT, prebiotics, probiotics, GLP-1 agonists, and ghrelin antagonists. Three studies involved AUD patients with concurrent ALD; the remainder focused on AUD alone.
Effect magnitude
No meta-analysis or pooled effect estimate was performed. Individual effect sizes were not consolidated. No aggregate 95% CI was reported.
Risk of bias
Included studies are small, most with sex imbalance (male predominance), some lack placebo controls, and follow-up is short. No risk-of-bias tool is explicitly named (RoB 2 or ROBINS-I not declared). The review itself does not conduct meta-analysis, limiting quantitative synthesis.
What this study does NOT prove
This review does not prove causality between microbiota modulation and AUD reduction, nor does it generalize findings to women, non-Western populations, or patients with severe psychiatric comorbidities. It does not establish optimal dose, duration, or strain for any intervention.
In clinical practice
Evidence is insufficient to incorporate FMT, probiotics, prebiotics, or GLP-1 agonists as standard AUD treatment. Clinicians should maintain approved pharmacotherapies (naltrexone, acamprosate, disulfiram) as the backbone. Gut health assessment may be considered in AUD patients with ALD only within controlled trial settings.
Limitations
Included studies are small, most with sex imbalance (male predominance), some lack placebo controls, and follow-up is short. No risk-of-bias tool is explicitly named (RoB 2 or ROBINS-I not declared). The review itself does not conduct meta-analysis, limiting quantitative synthesis.
What is still missing
Large-scale, placebo-controlled randomized trials with sex stratification and minimum 12-month follow-up are needed to validate each intervention individually and define responder profiles.
Technical appendix
Version history
- 1.0 · 2026-10-08 — Auto-generated under Evidence Standard v1.0