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Do probiotics improve vagal function in depression?

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In an RCT of 43 depressed patients and 43 controls, three months of a multi-species probiotic lowered morning heart rate and raised morning RMSSD/lnHF in depression versus placebo, with more Akkermansia and better sleep metrics.

Source

Multi-species probiotic supplement enhances vagal nerve function - results of a randomized controlled trial in patients with depression and healthy controls

Mörkl S, Narrath M, Schlotmann D, et al. · Gut microbes · 2025

doi.org/10.1080/19490976.2025.2492377Read the full paper ↗31 citationscc by

Study at a glance

Design
RCT — Randomized placebo-controlled trial of OMNi-BiOTiC STRESS Repair twice daily in MD vs healthy controls; 24-h HRV, stool 16S, sleep; NCT-04772664
N
N=86 · 43 major-depression patients and 43 healthy controls randomized to probiotic or placebo; 148 screened
Population
Adults 18–65 with ICD-10 major depression (on usual care) and healthy controls
Outcome
Vagus nerve function by 24-h HRV (morning RMSSD/lnHF/heart rate), microbiome, and sleep

Structured fields used in claim comparison tables when every cited study has a complete layer.

What they did

Randomized MD and healthy adults to OMNi-BiOTiC STRESS Repair or placebo twice daily, collecting 24-h ECG/HRV, stool 16S, serum, and questionnaires at baseline, 7 days, 28 days, and 3 months (NCT-04772664).

What they found

MD had higher heart rate and lower 24-h pNN50/RMSSD/SDNN than controls. After 3 months, MD on probiotic vs placebo had lower morning heart rate (t(33)=3.23, p=.003, d=1.10) and higher morning RMSSD (p=.002) and lnHF (p=.001), plus more Christensenellales/Akkermansia and improved PSQI sleep latency/medication use.

The limits

What it doesn't show

Adjunctive probiotics are not a stand-alone antidepressant trial; sample is modest, MD stayed on usual psychotropics, and abstract ‘vs HC’ wording is looser than the placebo-contrast results.

Key terms

Vagus nerve (VN) / HRV
Cardiac autonomic markers (RMSSD, pNN50, lnHF, RSA) used here as a proxy of vagal function.
Multi-species probiotic
OMNi-BiOTiC STRESS Repair given twice daily versus placebo.
RMSSD
Root mean square of successive R-R differences; higher values indicate greater vagal modulation.
Akkermansia muciniphila
Mucin-degrading gut microbe that increased in MD participants on probiotic.
NCT-04772664
ClinicalTrials.gov registration for this Graz RCT.

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Enrollment was about:

Common questions

Who was enrolled?

43 MD patients and 43 healthy controls (148 screened).

What was the primary endpoint?

Change in vagus function assessed by HRV.

What happened to morning HR in MD at 3 months?

Lower on probiotic than placebo (p=.003, d=1.10).

Which microbe increased?

Christensenellales, particularly Akkermansia muciniphila.

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