Epidemiological Study Exploring the Role of Human Gut Microbiome in the Prevalence of Type 2 Diabetes Across Different Communities of India

Kumar, Gauraw (2025) Epidemiological Study Exploring the Role of Human Gut Microbiome in the Prevalence of Type 2 Diabetes Across Different Communities of India. PhD thesis, Indian Institute of Science Education and Research Kolkata.

Text (PhD thesis of Gauraw Kumar (19RS017)) 19RS017.pdf - Submitted Version Restricted to Repository staff only Download (11MB)

Abstract

India has the second-largest diabetic population globally, and the number is increasing rapidly. Beyond known risk factors, emerging factors like the gut microbiome may shed light on the development and prevalence of Type 2 Diabetes (T2D). A survey of 353 individuals across West Bengal, Tripura, and Jharkhand revealed traditional risk factors could not fully explain the observed high prevalence of T2D. This led to the investigation of the gut microbiome, starting with the standardization of methods for sample collection, preservation, and sequencing chemistry. Acetone and 95% ethanol were identified as cost-effective fixatives which could resolve the issues of geographical remoteness and sustainable sampling. Significant variations in bacterial abundance across taxonomic levels were observed between sequencing chemistry (Illumina and Nanopore). Publicly available datasets from the USA, Chile, South Africa, Kuwait, and Malaysia were analyzed, revealing distinct geographical microbiome patterns influenced by ethnicity, lifestyle, and geography. Significant differences in microbiome composition across countries were observed (PERMANOVA, R2 = 0.28, p<0.001). In the Indian cohorts (60 individuals from Jharkhand, West Bengal, and Tripura), significant differences in gut microbiome profiles were found between healthy and T2D groups (p<0.001), indigenous and non-indigenous groups (p<0.01), and across states (p<0.001). A notably low Firmicutes to Bacteroidetes (F:B) ratio (0.227) was observed, with Firmicutes abundance differing between T2D and healthy groups (p=0.046) as well as higher Proteobacteria abundance in the T2D group. Linear discriminant analysis (LEfSe) showed enrichment of Bacteroides, Phascolarctobacterium, and Alistipes in West Bengal cohorts. The effects of diet on gut microbiome were examined through short-term interventions with one vegetarian participant and one non-vegetarian participant. Despite significant microbiome differences (p<0.001), short-term dietary changes did not account for the variations, suggesting that long-term dietary patterns may have a greater impact. This study highlights the complexity of T2D in India, where unique dietary patterns and early onset may influence gut microbiome profiles and thereby contributing to the disease's prevalence.

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