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Metformin Alters Upper Small Intestinal Microbiota that Impact a Glucose-SGLT1-Sensing Glucoregulatory Pathway
Open accessAbstract
The gut microbiota alters energy homeostasis. In parallel, metformin regulates upper small intestinal sodium glucose cotransporter-1 (SGLT1), but whether changes of the microbiota or SGLT1-dependent pathways in the upper small intestine mediate metformin action is unknown. Here we report that upper small intestinal glucose sensing triggers an SGLT1-dependent pathway to lower glucose production in rodents. High-fat diet (HFD) feeding reduces glucose sensing and SGLT1 expression in the upper small intestine. Upper small intestinal metformin treatment restores SGLT1 expression and glucose sensing while shifting the upper small intestinal microbiota partly by increasing the abundance of Lactobacillus. Transplantation of upper small intestinal microbiota from metformin-treated HFD rats to the upper small intestine of untreated HFD rats also increases the upper small intestinal abundance of Lactobacillus and glucose sensing via an upregulation of SGLT1 expression. Thus, we demonstrate that metformin alters upper small intestinal microbiota and impacts a glucose-SGLT1-sensing glucoregulatory pathway.
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“animal studies revealed that metformin’s glucoregulatory role was an effect of increased Lactobacilli abundance in the upper small intestine, while its anti-inflammatory role was associated with increased abundance of Akkermansia, Bacteroides, Butyricimonas, and Parabacteroides genera”
From Benefits of Metformin in Attenuating the Hallmarks of Aging (2020) · cites this paper as Bauer et al. 2018
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Metadata
- Authors
- Bauer, P. V., Duca, F. A., Waise, T. M. Z., Rasmussen, B. A., Abraham, M. A., Dranse, H. J., Puri, A., O’Brien, C. A., & Lam, T. K. T.
- Affiliations
- University Health Network (CA)
- Corresponding author
- Lam, Tony K.T.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2018-01
- Volume
- 27
- Issue
- 1
- Pages
- 101-117.e5
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2765695466
- Cited by
- 265
- References
- 123
- Citations by year
- 2026: 15 · 2025: 23 · 2024: 27 · 2023: 47 · 2022: 36 · 2021: 37 · 2020: 31 · 2019: 25 · 2018: 22
- FWCI
- 8.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research (FDN-143204)
- Banting and Best Diabetes Centre, University of Toronto
- Diabetes Canada
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- metformin, gut microbiota, upper small intestine, SGLT1, glucose detection, glucoregulation, glucose production, high-fat diet, Lactobacillus, microbiota transplantation, energy homeostasis
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Gastrointestinal Microbiome, Animals, Feeding Behavior, Glucose, Intestine, Small, Metformin, Principal Component Analysis, Sodium-Glucose Transporter 1, Rats, Glucagon-Like Peptide 1, Diet, High-Fat
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