# Identifying Immune Cells as Mediators in the Impact of Gut Microbiota on Congenital Malformations of the Nervous System

## TL;DR

This study shows that gut microbes can influence birth defects in the nervous system, with immune cells acting as key mediators, suggesting new ways to prevent or treat these conditions.

## Contribution

The study identifies specific immune cells as mediators of gut microbiota effects on congenital nervous system malformations using a two-step Mendelian randomization approach.

## Key findings

- 19 gut microbiota indicators were causally linked to congenital nervous system malformations.
- Nine immune cell indicators, including CD20+ and CD25+ B cells, significantly mediated these effects.
- Eubacteriaceae and Eubacterium showed protective effects, while Escherichia and Bacteroides increased malformation risk.

## Abstract

Congenital malformations of the nervous system, such as neural tube defects, are significant contributors to infant morbidity and mortality. This study aimed to assess the causal influence of gut microbiota on nervous system malformations and to identify immune cells as potential mediators in this relationship, utilizing a two‐step Mendelian randomization (TSMR) approach.

Using genome‐wide association studies data on gut microbiota, immune cells, and congenital malformations of the nervous system, we applied TSMR to evaluate the total, direct, and mediating effects. Gut microbiota indicators served as exposures, congenital malformations of the nervous system as outcomes, and immune cell markers as mediators. Statistical analyses included MR Egger, inverse variance weighted, and so forth.

Our analysis identified 19 gut microbiota indicators causally associated with congenital malformations of the nervous system. Notably, Eubacteriaceae and Eubacterium genera exhibited protective effects, while Escherichia and Bacteroides genera showed positive correlations with malformation risk. Nine immune cell indicators significantly mediated these effects. For example, CD20+ B cells were negatively associated with malformation risk, suggesting a protective immune response, whereas CD25+ B cells were positively correlated, indicating increased malformation risk.

This study demonstrated a significant link between gut microbiota composition and congenital nervous system malformations, mediated by specific immune cells. These findings highlighted the potential for gut microbiota modulation and immune‐targeted therapies as preventive or therapeutic strategies in reducing malformation risks. Future investigations should aim to replicate these results across diverse populations and further elucidate the underlying biological mechanisms of gut–immune–neural interactions.

The authors have nothing to report.

This study reveals causal links between gut microbiota and congenital nervous system malformations, identifying nine immune cell types, such as CD20+ and CD25+ B cells, as mediators, highlighting gut–immune interactions as potential preventive or therapeutic targets.