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The Gut Microbiome and Type 2 Diabetes Mellitus: Discussing a Complex Relationship.

ABSTRACT: Type 2 diabetes mellitus (T2DM) is a disease that affects over 9% of the United States population and is closely linked to obesity. While obesity was once thought to stem from a sedentary lifestyle and diets high in fat, recent evidence supports the idea that there is more complexity pertinent to the issue. The human gut microbiome has recently been the focus in terms of influencing disease onset. Evidence has shown that the microbiome may be more closely related to T2DM than what was originally thought. High fat diets typically result in poor microbiome heath, which then shifts the gut into a state of dysbiosis. Dysbiosis can then lead to metabolic deregulation, including increased insulin resistance and inflammation, two key factors in the development of T2DM. The purpose of this review is to discuss how microbiome relates to T2DM onset, especially considering obesity, insulin resistance, and inflammation.

SUBMITTER: Sikalidis AK

PROVIDER: S-EPMC7168169 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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The Gut Microbiome and Type 2 Diabetes Mellitus: Discussing a Complex Relationship.

Sikalidis Angelos K AK Maykish Adeline A

Biomedicines 20200107 1

Type 2 diabetes mellitus (T2DM) is a disease that affects over 9% of the United States population and is closely linked to obesity. While obesity was once thought to stem from a sedentary lifestyle and diets high in fat, recent evidence supports the idea that there is more complexity pertinent to the issue. The human gut microbiome has recently been the focus in terms of influencing disease onset. Evidence has shown that the microbiome may be more closely related to T2DM than what was originally ...[more]

PMID: 31936158

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Project description:BackgroundThe coexistence of hypertension and type 2 diabetes mellitus (T2DM) may largely increase the risk for cardiovascular disease. However, there is no clear consensus on the association between hypertension and the risk of diabetes. Gut microbiota plays important roles in the development of hypertension and T2DM, but whether there is difference between hypertension patients with or without T2DM has not been explored yet.MethodsWe recruited 101 hypertension patients in this study (72 patients without T2DM named HT group and 29 patients with T2DM named HT-T2DM group). Their blood samples were collected for testing clinical characteristics and fecal samples were tested for bacterial DNA using 16 S ribosomal RNA gene sequencing targeting the V3 and V4 region. The data of 40 samples were downloaded from project PRJNA815750 as health control (HC group) in this study. The community composition and structure of the microbiome, taxonomic difference, co-occurrence network and functional enrichment were analyzed by alpha/beta diversity, LEfSe, Fruchterman Reingold's algorithm and PICRUSt2 functional analysis, respectively.ResultsAlpha and beta diversity analysis showed significant differences in microbial community richness and composition among the three groups. The HC group had a significantly higher Simpson index and a distinct microbiota community compared to the HT and HT-T2DM groups, as demonstrated by significant differences in unweighted and weighted UniFrac distances. The LEfSe analysis identified specific taxa that had significantly different abundance among the groups, such as Bacteroides uniformis, Blautia wexlerae, Alistipes putredinis, and Prevotella stercorea in the HC group, Prevotella copri and Phascolarctobacterium faecium in the HT group, and Klebsiella pneumoniae in the HT-T2DM group. Co-occurrence network analysis indicates that Prevotella copri, Mediterraneibacter gnavus, Alistipes onderdonkii and some unidentified species act as key nodes in the network. Differentially functional pathway identified by PICRUSt2 were concentrated in nutrition and energy metabolism, as well as the biosynthesis of other secondary metabolites.ConclusionsOur study found significant differences in microbial community richness, composition, and function among the healthy controls, hypertension patients with and without T2DM. Some specific taxa may explain this difference and serve as potential therapeutic targets for hypertension, T2DM, and their coexistence.

Project description:PurposeThe purpose of this study is to investigate the relationship between the susceptibility to type 2 diabetes and gut microbiota in rats and to explore the potential mechanism involved.MethodsThirty-two SPF-grade SD rats were raised as donor rats, and divided into control, type 2 diabetes mellitus (T2DM, fasting blood glucose ≥ 11.1 mmol/L), and Non-T2DM (fasting blood glucose < 11.1 mmol/L) groups. Feces were collected and prepared as fecal bacteria supernatants Diab (fecal bacteria supernatant of T2DM group rats), Non (fecal bacteria supernatant of Non-T2DM group rats), and Con (fecal bacteria supernatant of control group rats). Another seventy-nine SPF-grade SD rats were separated into normal saline (NS) and antibiotics (ABX) groups and given normal saline and antibiotics solutions, respectively. In addition, the ABX group rats were randomly separated into ABX-ord (fed with a 4-week ordinary diet), ABX-fat (fed with a 4-week high-fat diet and STZ ip), FMT-Diab (with transplanted fecal bacteria supernatant Diab and fed with a 4-week high-fat diet and STZ ip), FMT-Non (with transplanted fecal bacteria supernatant Non and fed with a 4-week high-fat diet and STZ ip), and FMT-Con (with transplanted fecal bacteria supernatant Con and fed with a 4-week high-fat diet and STZ ip) groups. Furthermore, the NS group was randomly divided into NS-ord (fed with a 4-week ordinary diet) and NS-fat (fed with a 4-week high-fat diet and STZ ip) groups. After this, the short-chain fatty acids (SCFAs) in the feces were detected using gas chromatography, and the gut microbiota were detected using 16S rRNA gene sequencing. Finally, G protein-coupled receptor 41 (GPR41) and GPR43 were detected by western blot and quantitative real-time polymerase chain reaction.ResultsG__Ruminococcus_gnavus_group were more abundant in the FMT-Diab group compared to the ABX-fat and FMT-Non groups. The levels of blood glucose, serum insulin, total cholesterol, triglycerides, and low-density lipoprotein cholesterol were also higher in the FMT-Diab group compared to those of the ABX-fat group. Compared to the ABX-fat group, both the FMT-Diab and FMT-Non groups had higher contents of acetic and butyric acid, and the expression of GPR41/43 were significantly higher as well.ConclusionsG__Ruminococcus_gnavus_group might make rats more susceptible to T2DM; T2DM-susceptible flora transplantation increased the susceptibility to T2DM in rats. Additionally, gut microbiota-SCFAs-GPR41/43 may play a role in the development of T2DM. Lowering blood glucose by regulating gut microbiota may therefore become a new strategy for the treatment of T2DM in humans.

Dataset Information

The Gut Microbiome and Type 2 Diabetes Mellitus: Discussing a Complex Relationship.

Publications

The Gut Microbiome and Type 2 Diabetes Mellitus: Discussing a Complex Relationship.

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