Abstract
Type 2 diabetes mellitus (T2DM) is a complex disorder comprehensively influenced by genetic and environmental risk, and research increasingly has indicated the role of microbial dysbiosis in T2DM pathogenesis. However, studies comparing the microbiome characteristics between T2DM and healthy controls have reported inconsistent results. To further identify and describe the characteristics of the intestinal flora of T2DM patients, we performed a systematic review and meta-analysis of stool microbial profiles to discern and describe microbial dysbiosis in T2DM and to explore heterogeneity among 7 studies (600 T2DM cases, 543 controls, 1143 samples in total). Using a random effects model and a fixed effects model, we observed significant differences in beta diversity, but not alpha diversity, between individuals with T2DM and controls. We identified various operational taxonomic unit (OTUs) and bacterial genera with significant odds ratios for T2DM. The T2DM signatures derived from a single study by stepwise feature selection could be applied in other studies. By training on multiple studies, we improved the detection accuracy and disease specificity for T2DM. We also discuss the relationship between T2DM-enriched or T2DM-depleted genera and probiotics and provide new ideas for diabetes prevention and improvement.
Highlights
According to the 2019 Ninth International Diabetes Federation Diabetes Atlas, there are approximately 463 million diabetic patients worldwide [1]
Studies were included if they met the following inclusion criteria: 1) studies were based on human fecal samples from Type 2 diabetes mellitus (T2DM) patients and healthy subjects; 2) samples were sequenced by NGS for the 16S rRNA gene; and 3) raw sequencing data, barcodes, and metadata were publicly available or provided by the authors until October 20, 2020 upon request by email
Samples were distinctly clustered primarily by individual studies in principal coordinates analysis (PCoA) (Figure 1), probably due to different populations worldwide, as well as strong variables such as DNA extraction methods, 16S rRNA gene regions investigated, and sequencing platforms adopted by individual studies
Summary
According to the 2019 Ninth International Diabetes Federation Diabetes Atlas, there are approximately 463 million diabetic patients worldwide [1]. Gut Bacterial Characteristics of T2DM mellitus (T2DM) characterized by glucose intolerance accounts for approximately 90% of all diabetic patients worldwide [2, 3], and is a complex multifactorial metabolic disorder involving genetic (e.g. Tcf7l2, Kcnq1) and environmental lifestyle factors (e.g. intake of energy-dense refined food, sedentary behavior) [4,5,6,7]. The imbalance between immune cells results in the production of excess chemokines and proinflammatory cytokines that promote systemic inflammation and lead to peripheral insulin resistance. This immunological dysfunction leads to diabetic patients being more risky toward many infectious diseases (diabetic foot, diabetic nephropathy, et al.) [8, 9]. The study of pathological mechanisms is of great significance for the effective prevention and treatment of T2DM
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