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Life
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Microbiome–Gut–Brain Connections: New Windows into Health and Disease
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Microbiome–Gut–Brain Connections: New Windows into Health and Disease

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Microbiology".

Deadline for manuscript submissions: 31 January 2026 | Viewed by 2135

Special Issue Editors

Dr. Yating Wan

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Guest Editor
Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
Interests: gut microbes; gut-brain axis; neuroscience; neurological conditions
Dr. Qi Su

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Guest Editor
Department of Medicine & Therapeutics Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
Interests: microbiome; gastrointestinal diseases; mental disorders

Special Issue Information

Dear Colleagues,

As science and technology advance, more and more research has noted that the trillions of microbes inhabiting the gastrointestinal tract profoundly affect the extra-intestinal organs, especially the brain. Crosstalk between the gut microbes and the brain relies on the microbiome–gut–brain axis, which involves several pathways, including 1) microbe-induced neuroimmune responses in the central nervous system, 2) microbe-derived chemical signals directly affecting brain function, and 3) the neuronal messengers transmitted from gut to brain via neural afferent connections. Gut microbes play an essential role in brain development via participating in neurogenesis, myelination, and microglial maturation. However, the disruption of gut microbes related to increased pathogenic microbes and gut permeability further impairs the integrity of the blood–brain barrier. This compromise allows peripheral neurotoxic metabolites to enter the brain, leading to neuronal damage or neuroinflammation.

The link between gut microbes and brain health could be key to helping us understand, test, and treat relevant diseases. A broad spectrum of studies across diverse geographical regions and populations have revealed that altered gut microbiota profiles are associated with various neurological conditions, such as autism, epilepsy, Alzheimer's disease, and Parkinson's disease. Treatments like probiotics/prebiotics, fecal microbiota transplantation, and special diets that reshape gut microbes have shown promise. Characterizing the mechanisms of microbiome–gut–brain pathways is essential to elucidating the importance of gut microbes in neurological development and dysfunction; providing early tests and offering more effective management of diseases, is also of importance here. In this Special Issue, advances will be presented in understanding the microbiome–gut–brain connections and exploring their potential in clinical practice.

Dr. Yating Wan
Dr. Qi Su
Guest Editors

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Keywords

  • gut microbes
  • gut–brain axis
  • neuroscience

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Published Papers (3 papers)

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34 pages, 1463 KB  
Review
Brain Structures, Circuits, and Networks Involved in Immune Regulation, Periodontal Health, and Disease
by Torbjørn Jarle Breivik, Per Gjermo, Per Kristian Opstad, Robert Murison, Stephan von Hörsten and Inge Fristad
Life 2025, 15(10), 1572; https://doi.org/10.3390/life15101572 - 9 Oct 2025
Abstract
The interaction between microorganisms in the dental microfilm (plaque) at the gingival margin, the immune system, and the brain is vital for gingival health. The brain constantly receives information regarding microbial composition and inflammation status through afferent nerves and the bloodstream. It modulates [...] Read more.
The interaction between microorganisms in the dental microfilm (plaque) at the gingival margin, the immune system, and the brain is vital for gingival health. The brain constantly receives information regarding microbial composition and inflammation status through afferent nerves and the bloodstream. It modulates immune responses via efferent nerves and hormonal systems to maintain homeostasis. This relationship determines whether the gingiva remains healthy or develops into gingivitis (non-destructive inflammation) or periodontitis (a destructive condition), collectively referred to as periodontal disease. Factors associated with severe periodontitis heighten the responsiveness of this homeostatic system, diminishing the adaptive immune system’s defence against symbiotic microorganisms with pathogenic properties, known as pathobionts. This leads to excessive innate immune system activation, effectively preventing infection but damaging the periodontium. Consequently, investigating the microbiota–brain axis is vital for understanding its impact on periodontal health and disease. Herein, we examine recent advancements in how the defence against pathobionts is organised within the brain, and how it regulates and adapts the pro-inflammatory and anti-inflammatory immune balance, controlling microbiota composition. It also discussed how pathobionts and emotional stress can trigger neurodegenerative diseases, and how inadequate coping strategies for managing daily stress and shift work can disrupt brain circuits linked to immune regulation, weakening the adaptive immune response against pathobionts. Full article
(This article belongs to the Special Issue Microbiome–Gut–Brain Connections: New Windows into Health and Disease)
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30 pages, 3728 KB  
Systematic Review
Gut Microbiota and Obsessive–Compulsive Disorder: A Systematic Review of Mechanistic Links, Evidence from Human and Preclinical Studies, and Therapeutic Prospects
by Shayan Eghdami, Mahdieh Saeidi, Sasidhar Gunturu, Mahsa Boroon and Mohammadreza Shalbafan
Life 2025, 15(10), 1585; https://doi.org/10.3390/life15101585 - 10 Oct 2025
Abstract
Obsessive–compulsive disorder (OCD) is a multifactorial condition, and interest in gut–brain interactions is increasing. We conducted a systematic two-step review, registered in PROSPERO (CRD420251083936). Step 1 mapped core OCD biology to gut-relevant pathways, including neuroimmune activation, epithelial barrier function, microbial metabolites, and stress [...] Read more.
Obsessive–compulsive disorder (OCD) is a multifactorial condition, and interest in gut–brain interactions is increasing. We conducted a systematic two-step review, registered in PROSPERO (CRD420251083936). Step 1 mapped core OCD biology to gut-relevant pathways, including neuroimmune activation, epithelial barrier function, microbial metabolites, and stress circuitry, to clarify plausible mechanisms. Step 2 synthesized evidence from human and preclinical studies that measured or manipulated microbiota. Searches across PubMed, EMBASE, Web of Science, PsycINFO, and Cochrane (September 2025) yielded 357 biological and 20 microbiota-focused studies. Risk of bias was assessed using the Joanna Briggs Institute checklist for human studies and SYRCLE’s tool for animal studies. Although taxonomic findings in human cohorts were heterogeneous, functional patterns converged: reduced short-chain fatty acid capacity, enrichment of pro-inflammatory pathways, and host markers of barrier disruption and inflammation correlating with OCD severity. Transferring patient microbiota to mice induced OCD-like behaviors with neuroinflammatory changes, partly rescued by metabolites or barrier-supporting strains. Mendelian randomization suggested possible causal contributions at higher taxonomic levels. Diet, especially fiber intake, and psychotropic exposure were major sources of heterogeneity. Evidence supports the microbiota as a modifiable co-factor in a subset of OCD, motivating diet-controlled, stratified clinical trials with composite host–microbe endpoints. Full article
(This article belongs to the Special Issue Microbiome–Gut–Brain Connections: New Windows into Health and Disease)
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13 pages, 2262 KB  
Systematic Review
The Role of Gut Microbiota in Insomnia: A Systematic Review of Case–Control Studies
by Yun Wang, Suyi Xie, Sizhe Chen, Chenyu Li, Yeuk Lam Chan, Ngan Yin Chan, Yun Kwok Wing, Francis K. L. Chan, Qi Su and Siew C. Ng
Life 2025, 15(7), 1086; https://doi.org/10.3390/life15071086 - 10 Jul 2025
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Abstract
Background: Insomnia is one of the most prevalent health concerns and has a major impact on human health and quality of life. Increasing evidence indicates the gut microbiota’s role in sleep regulation through the gut–brain axis. This systematic review aims to summarise current [...] Read more.
Background: Insomnia is one of the most prevalent health concerns and has a major impact on human health and quality of life. Increasing evidence indicates the gut microbiota’s role in sleep regulation through the gut–brain axis. This systematic review aims to summarise current evidence on the role of gut microbiota alterations in insomnia. Methods: We searched PubMed, Embase, and Cochrane Library through November 2024 for case–control studies comparing gut microbiota in insomnia subjects and controls. The primary outcome was changes in microbiota diversity and bacteria taxonomy. Results: We included 15 case–control studies from 14 articles, consisting of 1321 subjects (603 insomnia; 718 controls). Eight studies showed reduced alpha diversity and eleven showed altered beta diversity in insomnia subjects. Depletions of specific taxa such as Lactobacillales (class Bacilli), Faecalibacterium, and Lachnospira and the enrichment of Actinobacteria, Bacteroidales (class Bacteroidia), and several genera, including Streptococcus, Blautia, Lactobacillus, Clostridium, Holdemanella, and Eubacterium hallii, were observed in insomnia subjects. There was a negative association between insomnia severity and abundance of Faecalibacterium and Lachnospira, and positive associations with Blautia. Conclusions: This systematic review identifies specific alterations in gut microbiota among insomnia subjects characterised by taxonomic changes that may serve as promising therapeutic targets for sleep disorders. Full article
(This article belongs to the Special Issue Microbiome–Gut–Brain Connections: New Windows into Health and Disease)
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