Cited by 266Gut microbiota and healthMetabolism, Diabetes, and CancerDiabetes Treatment and Management

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Metformin Alters Upper Small Intestinal Microbiota that Impact a Glucose-SGLT1-Sensing Glucoregulatory Pathway

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Bauer, Paige V., Duca, Frank A., Waise, T.M. Zaved, Rasmussen, Brittany A., Abraham, Mona A., Dranse, Helen J., Puri, Akshita, O’Brien, Catherine A., Lam, Tony K.T.·2018·Cell Metabolism

DOI 10.1016/j.cmet.2017.09.019

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Abstract

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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Self-citation

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.
ORCID: Duca, Frank A.
Waise, T.M. Zaved
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)
DOI: 10.1016/j.cmet.2017.09.019
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 374 d)
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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Metformin Alters Upper Small Intestinal Microbiota that Impact a Glucose-SGLT1-Sensing Glucoregulatory Pathway

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