Unraveling the gut microbiota-brain axis: Mechanisms, pathophysiology, and therapeutic opportunities
10 affiliations
- 1Anhui Provincial Key Laboratory of Animal Nutritional Regulation and Health, College of Animal Science, Anhui Science and Technology University, Chuzhou 233100, China
- 2Medical Microbiology and Immunology Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
- 3Department of Zoology, Wildlife and Fisheries, University of Agriculture Faisalabad 38000, Pakistan
- 4Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, USA
- 5National Laboratory for Veterinary Quality Control on Poultry Production, Animal Health Research Institute, Agriculture Research Center, Giza, Egypt
- 6Medical Microbiology and Immunology Department, Faculty of Medicine (for Girls), Al-Azhar University, Cairo, Egypt
- 7Pediatric Clinical Nutrition Division, Department of Pediatrics, Faculty of Medicine, Cairo University, Giza, Egypt
- 8National Key Laboratory of Agricultural Microbiology, College of Animal Sciences and Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China
- 9China Institute of Veterinary Drug Control, Beijing 102629, China
- 10Desert Research Center, Cairo 11435, Egypt
Abstract
The gut microbiota-brain axis constitutes a dynamic, bidirectional communication network that integrates neural, endocrine, immune, and metabolic pathways to regulate host physiology and behavior. Accumulating evidence indicates that disturbances within this axis have been consistently associated with metabolic, autoimmune, and neuropsychiatric disorders; however, much of the current evidence, particularly from human studies, remains largely correlative, and causal relationships are still under active investigation, highlighting its systemic relevance to health and disease. This review synthesizes current understanding of the structural and functional components of the gut microbiota-brain axis, including microbial community dynamics, neural signaling pathways, and key endocrine and immune mediators. We examine mechanistic insights into how microbial-derived metabolites influence brain function, cognition, mood regulation, stress responses, and disease pathogenesis. In addition, we discuss emerging therapeutic strategies targeting the gut microbiota-brain axis, including psychobiotics and fecal microbiota transplantation, while acknowledging dietary approaches, such as prebiotic supplementation, fiber-rich diets, and fermented food consumption, as complementary strategies that modulate microbiota composition that may indirectly support gut-brain axis function. By integrating mechanistic, clinical, and translational perspectives, this review aims to clarify current knowledge gaps and highlight future directions for leveraging the gut microbiota-brain axis in personalized approaches to neuropsychiatric disease management.
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BibTeX
@article{jiang2026unraveling,
title = {{Unraveling the gut microbiota-brain axis: Mechanisms, pathophysiology, and therapeutic opportunities}},
author = {Changsheng Jiang and Wedad M. Nageeb and Shumaila Batool and Amro Hashish and Sabah M. Alkhawagah and Hoda Atef Abdelsattar Ibrahim and Wenlong Zhu and Chuanyan Che and Xiaojin Li and Mengmeng Jin and Xiaoqian Zhang and Ahmed H. Ghonaim and Man Ren and Shenghe Li},
journal = {iScience},
year = {2026},
month = jun,
doi = {10.1016/j.isci.2026.116224},
url = {https://doi.org/10.1016/j.isci.2026.116224},
note = {CC BY},
}
RIS
TY - JOUR
TI - Unraveling the gut microbiota-brain axis: Mechanisms, pathophysiology, and therapeutic opportunities
AU - Changsheng Jiang
AU - Wedad M. Nageeb
AU - Shumaila Batool
AU - Amro Hashish
AU - Sabah M. Alkhawagah
AU - Hoda Atef Abdelsattar Ibrahim
AU - Wenlong Zhu
AU - Chuanyan Che
AU - Xiaojin Li
AU - Mengmeng Jin
AU - Xiaoqian Zhang
AU - Ahmed H. Ghonaim
AU - Man Ren
AU - Shenghe Li
PY - 2026
DA - 2026/06/01
JO - iScience
DO - 10.1016/j.isci.2026.116224
UR - https://doi.org/10.1016/j.isci.2026.116224
AB - The gut microbiota-brain axis constitutes a dynamic, bidirectional communication network that integrates neural, endocrine, immune, and metabolic pathways to regulate host physiology and behavior. Accumulating evidence indicates that disturbances within this axis have been consistently associated with metabolic, autoimmune, and neuropsychiatric disorders; however, much of the current evidence, particularly from human studies, remains largely correlative, and causal relationships are still under active investigation, highlighting its systemic relevance to health and disease. This review synthesizes current understanding of the structural and functional components of the gut microbiota-brain axis, including microbial community dynamics, neural signaling pathways, and key endocrine and immune mediators. We examine mechanistic insights into how microbial-derived metabolites influence brain function, cognition, mood regulation, stress responses, and disease pathogenesis. In addition, we discuss emerging therapeutic strategies targeting the gut microbiota-brain axis, including psychobiotics and fecal microbiota transplantation, while acknowledging dietary approaches, such as prebiotic supplementation, fiber-rich diets, and fermented food consumption, as complementary strategies that modulate microbiota composition that may indirectly support gut-brain axis function. By integrating mechanistic, clinical, and translational perspectives, this review aims to clarify current knowledge gaps and highlight future directions for leveraging the gut microbiota-brain axis in personalized approaches to neuropsychiatric disease management.
SN - 2589-0042
ER -