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

Gut Microbes. 2025 Dec;17(1):2492377. doi: 10.1080/19490976.2025.2492377. Epub 2025 Apr 29.

Abstract

Major depression (MD) significantly impacts individual well-being and society. The vagus nerve plays a pivotal role in the gut-brain axis, facilitating bidirectional communication between these systems. Recent meta-analyses suggest potential antidepressant effects of probiotics, although their mechanisms remain unclear. This study aimed to assess the impact of a multi-species probiotic (OMNi-BiOTiC® STRESS Repair) on vagus nerve function in 43 MD patients and 43 healthy controls (HC). Participants received either probiotics or placebo twice daily. Serum and stool samples were collected at baseline, 7 days, 28 days, and 3 months. Vagus nerve (VN) function was evaluated using 24-hour electrocardiography (ECG) for heart rate variability (HRV), alongside stool microbiome analysis via 16S rRNA sequencing. After 3 months, MD patients receiving probiotics demonstrated significantly improved morning VN function compared to HC. MD participants who were in the probiotic group showed a significant increase in Christensellales, particularly Akkermansia muciniphila along with improved sleep parameters (use of sleep medication, sleep latency) as measured by the Pittsburgh Sleep Quality Inventory (PSI). This study highlights potential physiological benefits of probiotics in MD, potentially mediated through VN stimulation. Understanding these mechanisms could lead to novel therapeutic approaches for MD management.

Keywords: Vagus nerve; depression; gut microbiome; heart rate variability; probiotic.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Akkermansia
  • Bacteria / classification
  • Bacteria / genetics
  • Bacteria / isolation & purification
  • Depressive Disorder, Major* / drug therapy
  • Depressive Disorder, Major* / microbiology
  • Depressive Disorder, Major* / physiopathology
  • Dietary Supplements
  • Feces / microbiology
  • Female
  • Gastrointestinal Microbiome / drug effects
  • Heart Rate / drug effects
  • Humans
  • Male
  • Middle Aged
  • Probiotics* / administration & dosage
  • Vagus Nerve* / drug effects
  • Vagus Nerve* / physiology
  • Vagus Nerve* / physiopathology

Supplementary concepts

  • Akkermansia muciniphila