Butyrate modulates diabetes-linked gut dysbiosis: epigenetic and mechanistic modifications
Abstract
Diabetic dysbiosis has been described as a novel key player in diabetes and diabetic complications. However, the cellular/molecular alterations associated with dysbiosis remain poorly characterized. For that, control, non-obese type 2 diabetic MKR mice and MKR mice treated with butyrate were used to delineate the epigenetic, cellular and molecular mechanisms by which dysbiosis associated with diabetes induces colon shortening and inflammation attesting to gastrointestinal disturbance. Our results show that dysbiosis is associated with T2DM and characterized by reduced Bacteroid fragilis population and butyrate-forming bacteria. The reduction of butyrate-forming bacteria and inadequate butyrate secretion result in alleviating HDAC3 inhibition and altering colon permeability. The observed changes are also associated with an increase in ROS production, a rise in NOX4 proteins, and a shift in the inflammatory markers, where IL-1β is increased and IL-10 and IL-17α are reduced. Treatment with butyrate restores the homeostatic levels of NOX4 and IL-1β. In summary, our data suggest that in T2DM, dysbiosis is associated with a reduction in butyrate content leading to increased HDAC3 activity. Butyrate treatment restores the homeostatic levels of the inflammatory markers and reduces ROS production known to mediate diabetes-induced colon disturbance. Taken together, our results suggest that butyrate could be a potential treatment to attenuate diabetic complications.
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A decrease in butyrate content is a characteristic of intestinal dysbiosis in diabetes.
“In addition, a recent review discusses the decrease in butyrate content as a characteristic of intestinal dysbiosis in diabetes (78).”
From Kefir and Intestinal Microbiota Modulation: Implications in Human Health (2021) · cites this paper as [78]
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Masse, K. E., & Lu, V. B. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1169624 · Cited by 120 · see citing works
Kefir and Intestinal Microbiota Modulation: Implications in Human Health
Peluzio, M. D. C. G., Dias, M. D. M. E., Martinez, J. A., & Milagro, F. I. (2021) · Frontiers in Nutrition · doi:10.3389/fnut.2021.638740 · Cited by 92 · see citing works
- Authors
- Noureldein, M. H., Bitar, S., Youssef, N., Azar, S., & Eid, A. A.
- Affiliations
- American University of Beirut Medical Center (LB)
- Venue
- Journal of Molecular Endocrinology
- Publisher
- Bioscientifica
- Published
- 2020-01
- Volume
- 64
- Issue
- 1
- Pages
- 29-42
- ISSN
- 0952-5041 (ISSN-L)
- 1479-6813
- OpenAlex
- W2991080771
- Cited by
- 84
- References
- 9
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 20 · 2023: 11 · 2022: 18 · 2021: 11 · 2020: 4
- FWCI
- 2.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Molecular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Keywords
- butyrate, type 2 diabetes, gut dysbiosis, butyrate-producing bacteria, HDAC3, histone deacetylase inhibition, reactive oxygen species, NOX4, IL-1β, IL-10, intestinal inflammation, epigenetic regulation
- MeSH terms
- Gastrointestinal Microbiome, Animals, Butyrates, Colon, Diabetes Mellitus, Inflammation, Intestinal Mucosa, Male, Biomarkers, Reactive Oxygen Species, Epigenesis, Genetic, Mice, Dysbiosis
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