# Gut microbiota 16S rRNA profiling with plasma and urine metabolomics in vestibular migraine

## TL;DR

This study explores gut microbiota and metabolomic differences in vestibular migraine patients compared to migraine patients and healthy controls.

## Contribution

The study is the first to use multi-omics to investigate gut microbiota and metabolomic profiles in vestibular migraine.

## Key findings

- VM patients showed distinct gut microbiota composition at the genus level compared to migraine patients and healthy controls.
- Plasma metabolomics revealed changes in pyruvate and amino acid metabolism in VM patients.
- Urine metabolomics linked tyrosine metabolism and norepinephrine to VM.

## Abstract

Vestibular migraine (VM) pathophysiology remains unclear, with research often extrapolating from migraine (M) studies. The microbiota-gut-brain axis represents a novel avenue for exploring VM mechanisms and treatments. This study aimed to compare gut microbiota, plasma and urine metabolome alterations among VM patients, M patients, and healthy controls (Hcs).

A cross-sectional study recruited 15 VM patients, 15 M patients, and 15 age-/gender-matched Hcs (April–September 2024) from a tertiary hospital. Final analysis included 10 VM, 15 M, and 15 Hc participants. All underwent fecal 16S rRNA gene sequencing, plasma and urine metabolomics. Demographic and clinical data were collected.

Gut microbiota alpha/beta diversity showed no significant inter-group differences. At the phylum level, Verrucomicrobiota and Chloroflexi were reduced in VM vs. M. Genus-level analysis revealed trends (e.g., decreased Akkermansia, increased Ruminococcus gnavus group in VM) and LEfSe (Linear Discriminant Analysis Effect Size) identified several genera (e.g., Latilactobacillus, Parvimonas) with higher relative abundance in VM. Plasma metabolomics identified numerous differential metabolites; bioinformatics implicated amino acid metabolism pathways, with pyruvate as a key differential metabolite. Urine metabolomics and bioinformatics strongly associated differential metabolites with tyrosine metabolism and norepinephrine (NE).

In this exploratory multi-omics study, VM patients showed distinct gut microbiota composition compared to M and HC, particularly at the genus level. Plasma metabolomics revealed alterations in pyruvate and amino acid metabolism pathways, suggesting possible energy metabolism disturbances in VM. Urine metabolomics highlighted the tyrosine metabolism pathway, with norepinephrine emerging as a metabolite of interest. These preliminary findings point to potential involvement of gut dysbiosis, metabolic perturbations, and neurotransmitter-related pathways in VM pathophysiology, providing a foundation for hypothesis-driven research. Given the exploratory nature of this study, these observations require validation in larger cohorts.