From Gut to Gains: How Microbiota-Modulated Protein Metabolism Enhances Muscle Function, Mitochondrial Health, and Metabolic Syndrome

Abstract

Background: Age-related sarcopenia and metabolic syndrome (MetS) are linked to chronic inflammation and dysfunctional protein metabolism, increasingly attributed to gut microbiota dysbiosis.Objectives: To explore the roles of gut microbiota and microbial metabolites in modulating muscle protein synthesis, mitochondrial health, and their therapeutic implications for MetS.

Methods: A thematic synthesis of peer-reviewed studies (2013–2025) sourced from PubMed, Scopus, and Web of Science using keywords: gut microbiota, protein metabolism, mitochondria, muscle function, SCFAs, and sarcopenia.

Results: SCFAs (especially butyrate) improve mitochondrial function, reduce oxidative stress, and enhance IGF-1/mTOR signaling (Wang et al., 2023). Dysbiosis increases LPS and inflammatory cytokines (e.g., TNF-α), suppressing muscle protein synthesis (Yu et al., 2023).Probiotics (e.g., L. plantarum, B. longum) restore gut integrity and improve muscle function (Zhang et al., 2023).

Microbial metabolites (indoles, bile acids) promote muscle regeneration via FXR-FGF19 signaling (Li et al., 2024).Conclusions: The gut–muscle–mitochondria axis offers a novel approach to improve muscle health and metabolic flexibility in aging and MetS.

Keywords: gut–muscle axis, microbiota, SCFAs, mitochondria, probiotics, sarcopenia.

1. Introduction

Sarcopenia and MetS are global health challenges, particularly in aging populations. The gut microbiota is now recognized as a key regulator of nutrient absorption, inflammation, and muscle-mitochondrial crosstalk (Wang et al., 2023). Microbial metabolites like SCFAs, tryptophan derivatives, and bile acids modulate protein metabolism, defining the gut–muscle–mitochondria axis. This review synthesizes evidence on how microbiota-driven pathways impact muscle strength and metabolic health.

2. Methodology

Studies were identified via systematic searches of PubMed, Scopus, and Web of Science (2013–2025) using keyword combinations: gut microbiota, muscle function, protein intake, mitochondria, sarcopenia, and metabolic syndrome. Included studies reported microbiota-driven changes in muscle, mitochondrial, or metabolic outcomes in peer-reviewed journals.

3. Results and Thematic Synthesis

3.1 Gut–Muscle–Mitochondria Axis

• SCFAs(butyrate, acetate) activate AMPK/PGC-1α, enhancing mitochondrial biogenesis and reducing muscle atrophy markers (e.g., atrogin-1) (Wang et al., 2023).

3.2 Dysbiosis and Sarcopenia

• Increased intestinal permeabilityand LPS elevate pro-inflammatory cytokines (IL-6, TNF-α), inhibiting IGF-1/mTOR and promoting muscle wasting (Yu et al., 2023).

3.3 Probiotics and Anabolic Recovery

• plantarumTWK10 and B. longum LPPS23 improve muscle mass by reducing inflammation and preserving mitochondrial function (Zhang et al., 2023).

3.4 Microbial Metabolites

• Indole derivativesand bile acids enhance intestinal barrier function and stimulate FXR/FGF19, aiding muscle regeneration (Li et al., 2024).

4. Discussion

The gut microbiota regulates muscle mass via metabolite signaling. Key insights:

1. Probioticsand fermented proteins improve microbial diversity and reduce inflammation.
2. Combined interventions(prebiotics, resistance training) show promise but require personalized approaches.
3. Clinical gaps: Population-specific trials are needed, especially for elderly and MetS patients.

5. Conclusion

Key Takeaways:

• Gut microbes regulate muscle growth via SCFA and bile acid signaling.
• Dysbiosis exacerbates inflammation and sarcopenia.
• Probiotics + exercisesynergistically improve muscle health.

Call-to-Action:
Precision nutrition and microbiota-based therapies should be integrated into public health strategies for aging and MetS.

Supplementary Sections

Funding Statement: No external funding declared.
Author Contributions: Geoffrey O. Mosota (NativeInspire.Africa) – Conceptualization, Writing, Review.
Conflict of Interest: None.
Data Availability: All data cited are publicly available.
Acknowledgements: We thank contributing researchers and open-access platforms.

References

1. Wang, Y., et al. (2023). Progress of linking gut microbiota and musculoskeletal health. Microbial Ecology in Health & Disease. [DOI:10.1080/19490976.2023.2263207]
2. Yu, Y., et al. (2023). Intestinal microbiota and muscle mass loss. Frontiers in Physiology, 14, 1013–1025.
3. Zhang, Q., et al. (2023). Probiotics and muscle aging. Nutrients, 15(2), 498.
4. Li, Y., et al. (2024). Microbial-derived metabolites regulate muscle metabolism. Cell Reports Medicine, 5(3), 200–215.