Gut Microbiome Fermentation Determines the Efficacy of Exercise for Diabetes Prevention
Open accessAbstract
Exercise is an effective strategy for diabetes management but is limited by the phenomenon of exercise resistance (i.e., the lack of or the adverse response to exercise on metabolic health). Here, in 39 medication-naive men with prediabetes, we found that exercise-induced alterations in the gut microbiota correlated closely with improvements in glucose homeostasis and insulin sensitivity (clinicaltrials.gov entry NCT03240978). The microbiome of responders exhibited an enhanced capacity for biosynthesis of short-chain fatty acids and catabolism of branched-chain amino acids, whereas those of non-responders were characterized by increased production of metabolically detrimental compounds. Fecal microbial transplantation from responders, but not non-responders, mimicked the effects of exercise on alleviation of insulin resistance in obese mice. Furthermore, a machine-learning algorithm integrating baseline microbial signatures accurately predicted personalized glycemic response to exercise in an additional 30 subjects. These findings raise the possibility of maximizing the benefits of exercise by targeting the gut microbiota.
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Observational studies indicate that exercise changes gut microbiome composition in mice and humans.
“Observational studies show exercise alters gut microbiome composition in mice14 and humans15–18.”
From Exercise-induced microbiota metabolite enhances CD8 T cell antitumor immunity promoting immunotherapy efficacy (2025) · cites this paper as [18]
In the Liu study, responders displayed greater gene expression of functional pathways generating SCFAs and breaking down BCAAs.
“responders displayed greater gene expression of functional pathways generating SCFAs and breaking down BCAAs.”
From The athletic gut microbiota (2020) · cites this paper as [106]
In the Liu study, responders showed a decrease in fasting insulin and HOMA-IR values of −42.70% and −49.60%, respectively.
“Those that did respond showed a remarkable decrease in fasting insulin and Homeostatic Model Assessment of Insulin Resistance index values (− 42.70% and − 49.60%, respectively).”
From The athletic gut microbiota (2020) · cites this paper as [106]
In the Liu study, there was clear segregation in compositional and functional changes between exercise responders and non-responders, accompanied by distinct alterations in microbial metabolites.
“there was a clear segregation in compositional and functional changes between exercise responders and non-responders, accompanied by distinct alterations in microbial metabolites.”
From The athletic gut microbiota (2020) · cites this paper as [106]
In the Liu study, the microbial profiles of non-responders after exercise intervention shared more similarity with sedentary controls, suggesting maladaptation of gut microbiota in these individuals.
“Conversely the microbial profiles of non-responders after the exercise intervention shared more similarity with those of the sedentary controls, suggesting a maladaptation of gut microbiota in these individuals.”
From The athletic gut microbiota (2020) · cites this paper as [106]
In mice transplanted with microbiota from responders, glycemic control and insulin sensitivity substantially improved, whereas mice colonized with microbiota from non-responders showed no change.
“A substantial improvement in mice gavaged with microbiota from responders was mimicked in glycemic control and insulin sensitivity, in contrast to the lack of change in mice colonized with microbiota from non-responders.”
From The athletic gut microbiota (2020) · cites this paper as [106]
Liu and colleagues established a machine-learning model from baseline microbiome signatures that accurately predicted exercise outcomes with respect to glycemic control and insulin sensitivity.
“Liu and colleagues were able to establish a model based on a machine-learning algorithm from baseline microbiome signatures which accurately predicted the exercise outcomes with respect to glycemic control and insulin sensitivity.”
From The athletic gut microbiota (2020) · cites this paper as [106]
In prediabetic, medication-naive overweight men, approximately 30% responded poorly to exercise in terms of improvement in glycemic control and insulin sensitivity.
“Despite the overall metabolic benefits of the intervention, ~ 30% of subjects responded poorly to exercise in terms of improvement in glycemic control and insulin sensitivity.”
From The athletic gut microbiota (2020) · cites this paper as [106]
Together, the human and animal results indicate that exercise may impose a differential impact on the composition and function of the gut microbiota across individuals.
“Together, the results from both the human and animal studies indicate that exercise may impose a differential impact on the composition and function of the gut microbiota across individuals.”
From The athletic gut microbiota (2020) · cites this paper as [106]
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- Authors
- Liu, Y., Wang, Y., Ni, Y., Cheung, C. K. Y., Lam, K. S. L., Wang, Y., Xia, Z., Ye, D., Guo, J., Tse, M. A., Panagiotou, G., & Xu, A.
- Affiliations
- University of Hong Kong (HK)
- Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI) (DE)
- Guangdong Pharmaceutical University (CN)
- Corresponding author
- Tse, Michael Andrew
- Panagiotou, Gianni
- Xu, Aimin
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2020-01
- Volume
- 31
- Issue
- 1
- Pages
- 77-91.e5
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2990997421
- Cited by
- 405
- References
- 77
- Citations by year
- 2026: 44 · 2025: 70 · 2024: 66 · 2023: 69 · 2022: 61 · 2021: 65 · 2020: 27 · 2019: 2
- FWCI
- 13.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China
- National Basic Research Program of China
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- gut microbiota, physical activity, prediabetes, diabetes prevention, exercise resistance, insulin resistance, glucose homeostasis, short-chain fatty acids, branched-chain amino acids, fecal microbiota transplantation, machine learning, obesity, metabolic health
- MeSH terms
- Gastrointestinal Microbiome, Fecal Microbiota Transplantation, Machine Learning, High-Intensity Interval Training, Adult, Algorithms, Animals, Bacteria, Diet, Feces, Glucose, Humans, Insulin Resistance, Male, Mice, Inbred C57BL, Middle Aged, Prediabetic State, Mice, Metabolome
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