Abstract

Introduction:

The gut–brain axis represents a bidirectional communication network linking the gastrointestinal tract and central nervous system through neural, immune, and metabolic pathways. Increasing evidence implicates glial cells, including enteric glia, astrocytes, and microglia, as key mediators of microbiota-driven neuroimmune signaling. However, the extent and characteristics of glial involvement across gut–brain axis studies remain incompletely synthesized.

Aim:

This scoping review aimed to systematically map and summarize existing evidence on the roles of glial cells in microbiota-mediated gut–brain communication and neuroimmune regulation.

Methods:

A scoping review was conducted following PRISMA-ScR guidelines. Peer-reviewed articles published between 2005 and 2025 were identified from PubMed, Scopus, and Web of Science using predefined search terms related to gut microbiota, glial cells, and neuroimmune signaling. Inclusion criteria comprised experimental and observational studies involving enteric glia, astrocytes, or microglia in gut–brain axis contexts. Data extracted included study design, model organism, glial cell type, microbiota-related exposure, and neuroimmune outcomes. Descriptive statistical analyses were performed.

Results:

A total of n = 68 studies met the inclusion criteria, including 42 animal studies, 18 in vitro studies, and 8 human observational studies. Enteric glia were examined in 31% of studies, microglia in 46%, and astrocytes in 38% (some studies assessed multiple glial types). Microbial metabolites, particularly short-chain fatty acids, were reported to modulate glial inflammatory signaling in 54% of studies. Evidence of glial-mediated immune modulation influencing neuroinflammation or behavioral outcomes was reported in 61% of included studies.

Conclusion:

Current evidence supports a central role for glial cells as intermediaries in microbiota-driven gut–brain communication, particularly through immune and metabolic signaling pathways. This synthesis highlights glial cells as critical, yet under-integrated, components of the gut–brain axis and underscores their relevance as potential therapeutic targets in neuroinflammatory and neurodegenerative conditions.

Ethical considerations:

This study analyzed published data only and did not involve new experiments or human/animal participants.