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Pathogens
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Gut–Brain Axis in Neurodevelopment: Microbial Metabolites and Neurological Function
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Gut–Brain Axis in Neurodevelopment: Microbial Metabolites and Neurological Function

A special issue of Pathogens (ISSN 2076-0817).

Deadline for manuscript submissions: closed (31 January 2026) | Viewed by 8567

Editors

Dr. Xuesong Zhang

E-Mail Website
Guest Editor
1. Center for Advanced Biotechnology and Medicine, Rutgers University-New Brunswick, Piscataway, NJ 08854, USA
2. Division of Medicine, University College London, UK
Interests: microbiome; innate immunity; autoimmune diseases; gut–brain axis, Helicobacter pylori; bacterial pathogenesis; gastrointestinal carcinogenesis
Special Issues, Collections and Topics in MDPI journals
Dr. Ningning Li

E-Mail Website
Guest Editor
Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen 518107, China
Interests: tumor microenvironment; gut–brain axis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The gut–brain axis is an emerging interdisciplinary field that connects microbiology, neuroscience, immunology, and developmental biology. Recent research has revealed the critical role of gut microbiota and its metabolites in shaping neurodevelopment and influencing neurological function throughout life. Disruptions in the microbial ecosystem during key developmental windows have been associated with altered immune signaling, neuroinflammation, and susceptibility to neurological disorders.

This Joint Special Issue, a collaboration between Pathogens and NeuroSci, seeks to highlight cutting-edge research on the molecular and cellular mechanisms through which gut microbes and their bioactive compounds influence brain development and function. We welcome contributions that elucidate how microbial metabolites affect neural signaling, neuroimmune crosstalk, and behavioral outcomes. Particular attention will be given to studies employing innovative model systems to unravel host–microbe communication along the gut–brain axis, especially during early development or in the context of neurological diseases.

Aligned with the shared interests of both journals, this issue will emphasize microbial determinants, host pathways, and disease mechanisms, with the goal of integrating microbiological and neuroscientific perspectives. We aim to foster a collaborative dialog that advances our understanding of microbial contributions to neural health and disease and inspires novel diagnostic and therapeutic strategies.

In this Special Issue, original research articles and comprehensive reviews are welcome. Research areas may include (but are not limited to) the following:

  • Microbial-derived metabolites with neuroactive or neuroimmunomodulatory functions;
  • Interactions between gut microbiota and the central/peripheral nervous and immune systems;
  • Host genetic or environmental factors shaping the gut–brain axis;
  • The impact of antibiotics, diet, or probiotics on neurodevelopment via microbiome modulation;
  • Animal and human studies exploring microbiota–neurodevelopment links;
  • Neuroinflammation and microbial pathogenesis.

You may choose our Joint Special Issue in NeuroSci.

We look forward to receiving your contributions.

Dr. Xuesong Zhang
Dr. Ningning Li
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pathogens is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • microbiome
  • gut–brain axis
  • microbial metabolites
  • neurodevelopment
  • host–microbe interaction

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Published Papers (2 papers)

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Research

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16 pages, 1552 KB  
Article
Gut Microbiotas, Plasma Metabolites, and Autism Spectrum Disorder: A Bidirectional Mendelian Randomization Analysis
by Jiayi Zhou, Zhang Fu, Yunfei Gao, Caiyan An, Zhiqiang Zhang, Xin Zhong, Liusuyan Tian, Xiuyan Yang, Junjing Zhang, Qingyuan Zhang, Dilong Wang and Ningning Li
Pathogens 2025, 14(11), 1137; https://doi.org/10.3390/pathogens14111137 - 10 Nov 2025
Cited by 2 | Viewed by 1737
Abstract
Background: Previous studies have indicated that the gut microbiome and plasma metabolites play key roles in autism spectrum disorder (ASD), but their causal relationships remain unclear. Linkage disequilibrium score regression (LDSC) and Mendelian randomization (MR) are powerful tools for assessing genetic causality. [...] Read more.
Background: Previous studies have indicated that the gut microbiome and plasma metabolites play key roles in autism spectrum disorder (ASD), but their causal relationships remain unclear. Linkage disequilibrium score regression (LDSC) and Mendelian randomization (MR) are powerful tools for assessing genetic causality. This study uses LDSC and MR to investigate the genetic links between the gut microbiome and ASD and explore the mediating role of plasma metabolites. Methods: To explore the genetic relationships between the gut microbiome, plasma metabolites, and ASD, we obtained summary statistics from large-scale genome-wide association studies (GWAS). Gut microbiome data came from a MiBioGen consortium meta-analysis (N = 18,340), ASD data from the Danish Psychiatric Central Research Register (DPCRR) (N = 18,382), and plasma metabolite data from the Canadian Longitudinal Study of Aging (CLSA) (N = 8299). We applied LDSC and bidirectional MR to analyze the genetic associations between the gut microbiome and ASD and plasma metabolites and ASD. Mediation MR was used to assess the mediating role of plasma metabolites in the gut microbiome-ASD relationship. Results: LDSC analysis revealed significant genetic correlations between the gut microbiota Lachnospiraceae NK4A136 group and Sellimonas with ASD. Moreover, bidirectional MR demonstrated causal effects of five gut microbial genera on ASD risk, as indicated by inverse variance weighted (IVW) methods. Similarly, we identified 49 plasma metabolites that exhibited genetic correlations with ASD, and 58 metabolites had causal effects on ASD in MR analysis. Mediation analysis revealed that specific bacteria, Ruminiclostridium5, reduce the occurrence of ASD through metabolites Delta-CEHC and Docosadioate (C22-DC). Furthermore, Ruminococcaceae UCG005 and Sutterella modulate ASD by inhibiting Serotonin and N-acetyl-L-glutamine, respectively. Conclusions: This study provides evidence of a causal relationship between the gut microbiome and ASD, with plasma metabolites acting as a potential mediator. Our findings offer new insights into the causal mechanisms linking the gut microbiome and ASD and provide a theoretical foundation for microbiome-based therapeutic strategies. Full article
(This article belongs to the Special Issue Gut–Brain Axis in Neurodevelopment: Microbial Metabolites and Neurological Function)
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Review

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21 pages, 1813 KB  
Review
The Microbiota–Gut–Brain Axis in Autism: Associations, Causal Inference, and Interventions—A Narrative Review
by Zhiqiang Zhang, Wenkai Kang, Yu Mi, Xin Zhong and Yulong He
Pathogens 2025, 14(11), 1145; https://doi.org/10.3390/pathogens14111145 - 11 Nov 2025
Cited by 10 | Viewed by 6054
Abstract
Autism spectrum disorder is markedly heterogeneous and frequently accompanied by gastrointestinal symptoms that often correlate with behavioral phenotypes. Emerging evidence suggests that the microbiota–gut–brain axis may contribute to these associations through multiple bidirectional communication routes—including neural, immune, and endocrine pathways, as well as [...] Read more.
Autism spectrum disorder is markedly heterogeneous and frequently accompanied by gastrointestinal symptoms that often correlate with behavioral phenotypes. Emerging evidence suggests that the microbiota–gut–brain axis may contribute to these associations through multiple bidirectional communication routes—including neural, immune, and endocrine pathways, as well as microbial metabolites such as short-chain fatty acids and tryptophan–kynurenine intermediates. This narrative review synthesizes clinical, mechanistic, and interventional evidence published between January 2010 and July 2025, clarifies the extent to which current data support association versus causation, evaluates key confounding factors, summarizes evidence for interventions such as probiotics, prebiotics, and fecal microbiota transplantation, and outlines future directions for precision research and targeted interventions based on functional pathways and stratified subgroups. Full article
(This article belongs to the Special Issue Gut–Brain Axis in Neurodevelopment: Microbial Metabolites and Neurological Function)
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