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The Gut-Brain-Muscle Axis: Microbial Regulation of Neuromuscular Aging and Cognitive Frailty
Nurpudji Astuti Taslim1, Jeremy Nicolas Sibarani2, Ricky Indra Alfaray2,3,4
1Division of Clinical Nutrition, Department of Nutrition, Faculty of Medicine, Hasanuddin University, Makassar 90245, Indonesia.
Microorganisms
|June 26, 2026
Summary
The gut microbiota influences aging through the gut-brain-muscle axis, impacting physical and cognitive health. Interventions targeting this axis may promote healthy longevity.
Area of Science:
- Gerontology and Neuroscience
- Microbiology and Immunology
- Metabolic and Molecular Biology
Background:
- Cognitive frailty, a combination of physical frailty and cognitive impairment, is a growing concern in aging populations.
- It is increasingly linked to conditions like sarcopenia, neurodegeneration, and chronic inflammation.
- The gut microbiota is recognized as a key regulator of aging in the gut-brain-muscle axis.
Purpose of the Study:
- To review the role of the gut microbiota in cognitive frailty.
- To highlight the mechanisms through which microbial dysbiosis affects neuromuscular and neurocognitive aging.
- To explore potential therapeutic strategies targeting the gut-brain-muscle axis for healthy longevity.
Main Methods:
- Literature review focusing on the gut-brain-muscle axis and cognitive frailty.
- Analysis of signaling pathways involving microbial metabolites, cytokines, and myokines.
- Examination of exercise-induced effects and translational interventions.
Main Results:
- Microbial dysbiosis, reduced short-chain fatty acid (SCFA) production, and endotoxemia contribute to mitochondrial dysfunction, neuroinflammation, and impaired neuroplasticity.
- Bidirectional communication between the gut, muscle, and brain is mediated by SCFAs, bile acids, tryptophan metabolites, cytokines, and myokines (e.g., irisin, BDNF).
- Exercise can remodel the microbiota and enhance muscle signaling, promoting cognitive resilience.
Conclusions:
- The gut-brain-muscle axis offers a systems biology framework for understanding cognitive frailty.
- Interventions such as probiotics, prebiotics, postbiotics, and precision nutrition show promise for targeting this axis.
- Modulating the gut microbiota and its interactions holds potential for developing integrated strategies for healthy aging.
Keywords:
cognitive frailtygut microbiotagut–brain–muscle axismicrobial metabolitesmitochondriamyokinesneuroinflammationneuromuscular agingprecision nutritionsarcopeniaMore Related Videos
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