Trans-ethnic gut microbiota signatures of type 2 diabetes in Denmark and India

Abstract

Background Type 2 diabetes (T2D), a multifactorial disease influenced by host genetics and environmental factors, is the most common endocrine disease. Several studies have shown that the gut microbiota as a close-up environmental mediator influences host physiology including metabolism. The aim of the present study is to examine the compositional and functional potential of the gut microbiota across individuals from Denmark and South India with a focus on T2D. Many earlier studies have investigated the microbiome aspects of T2D, and it has also been anticipated that such microbial associations would be dependent on diet and ethnic origin. However, there has been no large scale trans-ethnic microbiome study earlier in this direction aimed at evaluating any “universal” microbiome signature of T2D. Methods 16S ribosomal RNA gene amplicon sequencing was performed on stool samples from 279 Danish and 294 Indian study participants. Any differences between the gut microbiota of both populations were explored using diversity measures and negative binomial Wald tests. Study samples were stratified to discover global and country-specific microbial signatures for T2D and treatment with the anti-hyperglycemic drug, metformin. To identify taxonomical and functional signatures of the gut microbiota for T2D and metformin treatment, we used alpha and beta diversity measures and differential abundances analysis, comparing metformin-naive T2D patients, metformin-treated T2D patients, and normoglycemic individuals. Results Overall, the gut microbial communities of Danes and Indians are compositionally very different. By analyzing the combined study materials, we identify microbial taxonomic and functional signatures for T2D and metformin treatment. T2D patients have an increased relative abundance of two operational taxonomic units (OTUs) from the Lachnospiraceae family, and a decreased abundance of Subdoligranulum and Butyricicoccus. Studying each population per se, we identified T2D-related microbial changes at the taxonomic level within the Danish population only. Alpha diversity indices show that there is no significant difference between normoglycemic individuals and metformin-naive T2D patients, whereas microbial richness is significantly decreased in metformin-treated T2D patients compared to metformin-naive T2D patients and normoglycemic individuals. Enrichment of two OTUs from Bacteroides and depletion of Faecalibacterium constitute a trans-ethnic signature of metformin treatment. Conclusions We demonstrate major compositional differences of the gut microbiota between Danish and South Indian individuals, some of which may relate to differences in ethnicity, lifestyle, and demography. By comparing metformin-naive T2D patients and normoglycemic individuals, we identify T2D-related microbiota changes in the Danish and Indian study samples. In the present trans-ethnic study, we confirm that metformin changes the taxonomic profile and functional potential of the gut microbiota.

Role of Postbiotics in Diabetes Mellitus: Current Knowledge and Future Perspectives

“…Human data on postbiotics and DM are lacking, and we identified only one trial on this topic in healthy adults [85]. It is likely that ethnic group [138,139], sex [140], and the time course of DM [141] influence the GM response to postbiotic treatments, and these aspects should be contemplated in human studies. Many of the included studies did not analyse the changes in the GM following the interventions, and this would provide valuable information about the underlying mechanisms.…”

Network analysis after epigenome wide methylation study revealed JUP as a regulator of co-methylated risk-module for T2DM

“…T2DM has multiple risk factors (e.g., high-fat diet, genetic susceptibility), and many of them are prevalent at the population level (4,5,6,7). Several of these factors can affect the disease risk through hypo- or hypermethylation of genes leading to alteration in specific gene expression (11,12,13,18). To identify these differentially methylated CpG sites, we performed an EWAS in 844 Indian individuals of Indo-European origin and explored the possible mechanism of associations by integrating epigenome-based co-methylation network analysis and methQTL analysis.…”

“…Existing evidence from genetic epidemiological studies and randomized control trials designed to intervene with T2DM risks suggest its multifactorial origin with significant contribution from genetic, environmental, and behavioral factors (3,4). Although, many of these causal factors are individual-specific (e.g., smoking, exercise) (5, 6,7,8), several others are population-specific (e.g., nature and content of diets, genetic component) (4, 9) as well as environment-specific (e.g., gut microbiome, sedentary lifestyle) (10,11) that significantly differ across different ethnic populations. These behavioral and environmental factors contribute to diabetes by controlling the gene expression through epigenetic mechanisms (e.g., DNA methylation, histone modification, chromatin remodeling) (12,13).…”

Diagnostic significance of serum lncRNA HOTAIR and its predictive value for the development of chronic complications in patients with type 2 diabetes mellitus

“…A total of 82 healthy subjects who received physical examinations in the same period were selected and set as the healthy control group. The inclusion criteria of the T2DM group were in accordance with the criteria for diagnosis and classification of diabetes recommended by the World Health Organization in 1999, namely fasting venous plasma glucose ≥ 7.0 mmol/L [20]. All participants had not received any antidiabetic drugs or insulin treatment before.…”