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          The flagship journal of the Society for Endocrinology. Learn more

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      New insights into the links between anti-diabetes drugs and gut microbiota

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          Abstract

          In patients with type 2 diabetes mellitus (T2DM), the intestinal flora is out of balance and accompanied by leaky gut. The flora is characterized by an increase in mucus-degrading bacteria and a decrease in fiber-degrading bacteria. Short-chain fatty acids (SCFAs), as the major fiber-degrading bacteria fermentation, not only ameliorate the leaky gut, but also activate GPR43 to increase the mass of functional pancreatic β-cells and exert anti-inflammation effect. At present, the gut microbiota is considered as the potential target for anti-diabetes drugs, and how to reverse the imbalance of gut microbiota has become a therapeutic strategy for T2DM. This review briefly summarizes the drugs or compounds that have direct or potential therapeutic effects on T2DM by modulating the gut microbiota, including biguanides, isoquinoline alkaloids, stilbene and C7N-aminocyclic alcohols.

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          A metagenome-wide association study of gut microbiota in type 2 diabetes.

          Junjie Qin, Yingrui Li, Zhiming Cai … (2012)
          Assessment and characterization of gut microbiota has become a major research area in human disease, including type 2 diabetes, the most prevalent endocrine disease worldwide. To carry out analysis on gut microbial content in patients with type 2 diabetes, we developed a protocol for a metagenome-wide association study (MGWAS) and undertook a two-stage MGWAS based on deep shotgun sequencing of the gut microbial DNA from 345 Chinese individuals. We identified and validated approximately 60,000 type-2-diabetes-associated markers and established the concept of a metagenomic linkage group, enabling taxonomic species-level analyses. MGWAS analysis showed that patients with type 2 diabetes were characterized by a moderate degree of gut microbial dysbiosis, a decrease in the abundance of some universal butyrate-producing bacteria and an increase in various opportunistic pathogens, as well as an enrichment of other microbial functions conferring sulphate reduction and oxidative stress resistance. An analysis of 23 additional individuals demonstrated that these gut microbial markers might be useful for classifying type 2 diabetes.
          Article 0 comments Cited 1811 times – based on 0 reviews     Review now
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            Proteobacteria: microbial signature of dysbiosis in gut microbiota.

            Na-Ri Shin, Tae Woong Whon, Jin-Woo Bae (2015)
            Recent advances in sequencing techniques, applied to the study of microbial communities, have provided compelling evidence that the mammalian intestinal tract harbors a complex microbial community whose composition is a critical determinant of host health in the context of metabolism and inflammation. Given that an imbalanced gut microbiota often arises from a sustained increase in abundance of the phylum Proteobacteria, the natural human gut flora normally contains only a minor proportion of this phylum. Here, we review studies that explored the association between an abnormal expansion of Proteobacteria and a compromised ability to maintain a balanced gut microbial community. We also propose that an increased prevalence of Proteobacteria is a potential diagnostic signature of dysbiosis and risk of disease.
            Article 0 comments Cited 1132 times – based on 0 reviews     Review now
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              Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice.

              P D Cani, R Bibiloni, C. Knauf … (2008)
              Diabetes and obesity are characterized by a low-grade inflammation whose molecular origin is unknown. We previously determined, first, that metabolic endotoxemia controls the inflammatory tone, body weight gain, and diabetes, and second, that high-fat feeding modulates gut microbiota and the plasma concentration of lipopolysaccharide (LPS), i.e., metabolic endotoxemia. Therefore, it remained to demonstrate whether changes in gut microbiota control the occurrence of metabolic diseases. We changed gut microbiota by means of antibiotic treatment to demonstrate, first, that changes in gut microbiota could be responsible for the control of metabolic endotoxemia, the low-grade inflammation, obesity, and type 2 diabetes and, second, to provide some mechanisms responsible for such effect. We found that changes of gut microbiota induced by an antibiotic treatment reduced metabolic endotoxemia and the cecal content of LPS in both high-fat-fed and ob/ob mice. This effect was correlated with reduced glucose intolerance, body weight gain, fat mass development, lower inflammation, oxidative stress, and macrophage infiltration marker mRNA expression in visceral adipose tissue. Importantly, high-fat feeding strongly increased intestinal permeability and reduced the expression of genes coding for proteins of the tight junctions. Furthermore, the absence of CD14 in ob/ob CD14(-)(/)(-) mutant mice mimicked the metabolic and inflammatory effects of antibiotics. This new finding demonstrates that changes in gut microbiota controls metabolic endotoxemia, inflammation, and associated disorders by a mechanism that could increase intestinal permeability. It would thus be useful to develop strategies for changing gut microbiota to control, intestinal permeability, metabolic endotoxemia, and associated disorders.
              Article 0 comments Cited 972 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Endocr Connect
                Journal ID (iso-abbrev): Endocr Connect
                Journal ID (hwp): EC
                Title: Endocrine Connections
                Publisher: Bioscientifica Ltd (Bristol )
                ISSN (Electronic): 2049-3614
                Publication date Collection: January 2021
                Publication date (Electronic): 17 December 2020
                Volume: 10
                Issue: 1
                Pages: R36-R42
                Affiliations
                [1 ]School of pharmacy , Qing Dao University, Qingdao, China
                Author notes
                Correspondence should be addressed to L Ji or G Jiang : lixiaji@ 123456163.com or 13370830026@ 123456163.com
                Article
                Publisher ID: EC-20-0431
                DOI: 10.1530/EC-20-0431
                PMC ID: 7923145
                PubMed ID: 33338029
                SO-VID: 485622ee-d203-4782-a190-f7453316a831
                Copyright © © 2021 The authors
                License:

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                Date received : 09 December 2020
                Date accepted : 17 December 2020
                Categories
                Subject: Review

                Keywords: gut microbiota,leaky gut,functional pancreatic β-cells,short-chain fatty acids (scfas),anti-diabetes drugs,type 2 diabetes mellitus (t2dm)
                Data availability:
                Keywords: gut microbiota, leaky gut, functional pancreatic β-cells, short-chain fatty acids (scfas), anti-diabetes drugs, type 2 diabetes mellitus (t2dm)

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