Gut Microbial Diversity Assessment of Indian Type-2-Diabetics Reveals Alterations in Eubacteria, Archaea, and Eukaryotes

Abstract

Diabetes in India has distinct genetic, nutritional, developmental and socio-economic aspects; owing to the fact that changes in gut microbiota are associated with diabetes, we employed semiconductor-based sequencing to characterize gut microbiota of diabetic subjects from this region. We suggest consolidated dysbiosis of eubacterial, archaeal and eukaryotic components in the gut microbiota of newly diagnosed (New-DMs) and long-standing diabetic subjects (Known-DMs) compared to healthy subjects (NGTs). Increased abundance of phylum Firmicutes (p = 0.010) and Operational Taxonomic Units (OTUs) of Lactobacillus (p < 0.01) were observed in Known-DMs subjects along with the concomitant graded decrease in butyrate-producing bacterial families like Ruminococcaceae and Lachnospiraceae. Eukaryotes and fungi were the least affected components in these subjects but archaea, except Methanobrevibacter were significantly decreased in them. The two dominant archaea viz. Methanobrevibacater and Methanosphaera followed opposite trends in abundance from NGTs to Known-DMs subjects. There was a substantial reduction in eubacteria, with a noticeable decrease in Bacteroidetes phylum (p = 0.098) and an increased abundance of fungi in New-DMs subjects. Likewise, opportunistic fungal pathogens such as Aspergillus, Candida were found to be enriched in New-DMs subjects. Analysis of eubacterial interaction network revealed disease-state specific patterns of ecological interactions, suggesting the distinct behavior of individual components of eubacteria in response to the disease. PERMANOVA test indicated that the eubacterial component was associated with diabetes-related risk factors like high triglyceride (p = 0.05), low HDL (p = 0.03), and waist-to-hip ratio (p = 0.02). Metagenomic imputation of eubacteria depict deficiencies of various essential functions such as carbohydrate metabolism, amino acid metabolism etc. in New-DMs subjects. Results presented here shows that in diabetes, microbial dysbiosis may not be just limited to eubacteria. Due to the inter-linked metabolic interactions among the eubacteria, archaea and eukarya in the gut, it may extend into other two domains leading to trans-domain dysbiosis in microbiota. Our results thus contribute to and expand the identification of biomarkers in diabetes.

Metagenomics analysis reveals features unique to Indian distal gut microbiota

“…Unsupervised clustering by PLSDA indicated clear separation of Indian subjects from subjects of other countries. We would like to note here that the previous metataxonomic profiling study by Bhute et al indicated Prevotella, Lactobacillus, Lachnospira and Roseburia to be overrepresented in urban and rural Indian subjects from Delhi and Pune as compared to American subjects [31].…”

“…Bhute et al showed the presence of Firmicutes as the major phylum in Indian subjects; other major phyla included Bacteroidetes, Proteobacteria and Actinobacteria [31]. Their study also indicated that Prevotella and Megasphaera were dominant genera [31].…”

“…Bhute et al showed the presence of Firmicutes as the major phylum in Indian subjects; other major phyla included Bacteroidetes, Proteobacteria and Actinobacteria [31]. Their study also indicated that Prevotella and Megasphaera were dominant genera [31]. Dehingia et al reported the presence of Firmicutes, Bacteoidetes and Actinobacteria as the major phyla across Manipur, Telangana, Assam and Sikkim regions of India, with the Manipur tribes having significantly more Bacteroidetes than Firmicutes and the Sikkim tribes having more Actinobacteria in comparison to the other tribes [30].…”

The Gut Microbial Diversity of Newly Diagnosed Diabetics but Not of Prediabetics Is Significantly Different from That of Healthy Nondiabetics

“…3). In NewDMs, Akkermansia, Blautia, and Ruminococcus showed significantly decreased abundance (P ϭ 0.0009 and log 2 FC ϭ Ϫ14.2, P ϭ 0.0009 and log 2 FC ϭ Ϫ2.52, and P ϭ 0.006 and log 2 FC ϭ Ϫ0.39, respectively), and a similar trend was observed for Prevotella (P ϭ 0.054 and not significant), one of the dominant genera found in Indian gut (19,21,22), while Lactobacillus (P ϭ 0.01 and log 2 FC ϭ 5.27) showed increased abundance compared to ND. Significantly increased abundance of Megasphaera (P ϭ 0.005 and log 2 FC ϭ 1.42), Escherichia (P ϭ 0.003 and log 2 FC ϭ 1.96), and Acidaminococcus (P ϭ 0.008 and log 2 FC ϭ 2.90) and decreased abundance of Sutterella (P ϭ 0.003 and log 2 FC ϭ Ϫ0.66), was observed in KnownDMs compared to ND.…”

“…An abundance of Prevotella showed positive correlation with histidine (P ϭ 0.025). Prevotella is one of the most dominant genera found in the Indian gut (19,21,22) and is inversely correlated with glucose, HbA1c, triglycerides, VLDL cholesterol, HDL cholesterol, leucine, tyrosine, methionine, IL-6, and lipid peroxides and positively correlated with total antioxidants; however, these associations were not found to be significant (P Ͼ 0.05). An abundance of genus Akkermansia showed strong inverse correlation with fasting glucose (P ϭ 0.04), HbA1c (P ϭ 0.008), leucine (P ϭ 0.04), and tryptophan (P ϭ 0.002) and a strong positive correlation with histidine (P ϭ 0.006) and total anti- ).…”