Cited by 24Gut microbiota and healthGastrointestinal motility and disordersTryptophan and brain disorders
Metagenomic symphony of the intestinal ecosystem: How the composition affects the mind
Open accessMalan-Müller, Stefanie, Martín-Hernández, David, Caso, Javier R., Matthijnssens, Jelle, Rodríguez-Urrutia, Amanda, Lowry, Christopher A., Leza, Juan C.·2025·Brain, Behavior, and Immunity
Abstract
Mental health disorders and neurodegenerative diseases place a heavy burden on patients and societies, and, although great strides have been made to understand the pathophysiology of these conditions, advancement in drug development is lagging. The importance of gastrointestinal health in maintaining overall health and preventing disease is not a new concept. Hundreds of years ago, healers from various cultures and civilizations recognized the crucial role of the gut in sustaining health. More than a century ago, scientists began exploring the restorative effects of probiotics, marking the early recognition of the importance of gut microbes. The omics era brought more enlightenment and enabled researchers to identify the complexity of the microbial ecosystems we harbour, encompassing bacteria, eukaryotes (including fungi), archaea, viruses, and other microorganisms. The extensive genetic capacity of the microbiota is dynamic and influenced by the environment. The microbiota therefore serves as a significant entity within us, with evolutionarily preserved functions in host metabolism, immunity, development, and behavior. The significant role of the bacterial gut microbiome in mental health and neurodegenerative disorders has been realized and described within the framework of the microbiota-gut-brain axis. However, the bacterial members do not function unaccompanied, but rather in concert, and there is a substantial knowledge gap regarding the involvement of non-bacterial microbiome members in these disorders. In this review, we will explore the current literature that implicates a role for the entire metagenomic ensemble, and how their complex interkingdom relationships could influence CNS functioning in mental health disorders and neurodegenerative diseases.
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Communication between gut and brain occurs through multiple interconnected neural, endocrine, immune, and metabolic pathways that can synergize to modulate AD risk and progression.
“Communication between the gut and brain occurs through multiple, interconnected pathways, including neural, endocrine, immune, and metabolic routes, that can synergize to modulate AD risk and progression [122].”
From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [122]
Section 2.1 (pp. 3–4) describes bidirectional gut–brain communication through neural, endocrine, immune, and microbial-metabolite routes. The discussion on p. 5 links herpes infections in the brain to Alzheimer’s disease risk and progression, but does not establish that the listed gut–brain pathways act synergistically to modulate that risk or progression. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe gut microbiota plays critical roles in metabolism, immune regulation, and neural signaling.
“The gut microbiota, consisting primarily of bacteria but also fungi, viruses, archaea, and protozoa, plays critical roles in metabolism, immune regulation, and neural signaling.”
From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [122]
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Cited by
Sorted by citations
Hein, Z. M., Karikalan, B., Gopalakrishna, P. K., Dhevi, K., Alkatiri, A., Hussan, F., Mohd Moklas, M. A., Jagadeesan, S., Che Ramli, M. D., Che Mohd Nassir, C. M. N., et al. (2026) · Molecular Neurobiology · doi:10.1007/s12035-025-05602-0 · Cited by 43 · see citing works
- Authors
- Malan-Müller, S., Martín-Hernández, D., Caso, J. R., Matthijnssens, J., Rodríguez-Urrutia, A., Lowry, C. A., & Leza, J. C.
- Affiliations
- Universidad Complutense de Madrid (ES)
- KU Leuven (BE)
- University of Colorado Boulder (US)
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2025-01
- Volume
- 123
- Pages
- 510-523
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W4403144355
- Cited by
- 24
- References
- 14
- Citations by year
- 2026: 8 · 2025: 15 · 2024: 1
- FWCI
- 0.94
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Brain Behavior and Immunity (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Lirias (KU Leuven) (submittedVersion, cc-by-nc)
- Funders
- H2020 Marie Skłodowska-Curie Actions (847635)
- Horizon 2020
- Brain and Behavior Research Foundation (27050)
- OpenAI
- Spain Ministry of Science and Innovation (PID2020-113103RB-I00, PID2021-126468OA-I00)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- gut microbiota, microbiota-gut-brain axis, mental illness, neurodegenerative diseases, metagenomics, protists, archaea, viruses, cross-kingdom interactions, probiotics, host-microbe interactions
- MeSH terms
- Gastrointestinal Microbiome, Brain-Gut Axis, Animals, Bacteria, Mental Disorders, Brain, Humans, Mental Health, Neurodegenerative Diseases, Probiotics, Metagenome, Metagenomics
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