Indian sewage microbiome has unique community characteristics and potential for population-level disease predictions.

Sewage wastewater pollutes water and poses a public health issue but it could also prove useful in certain research domains. Sewage is a complex niche relevant for research concerning 'one-health', human health, pollution and antibiotic resistance. Indian gut microbiome is also understudied due to sampling constraints and sewage could be used to explore it. Ostensibly, Indian sewage needs to be studied and here, we performed a cross-sectional pan-India sewage sampling to generate the first comprehensive Indian sewage microbiome. Indian sewage showed predominance of Burkholderiaceae, Rhodocyclaceae, Veillonellaceae, Prevotellaceae, etc. and has high representation of gut microbes. The identified gut microbes have overrepresentation of Veillonellaceae, Rikenellaceae, Streptococcaceae, and Bacillaceae. Imputed metagenomics of sewage microbiome indicated dominance of transport, motility, peptidases, amino acid metabolism, and antibiotic resistance genes. Microbiome-disease associations drawn using simple decision tree and random forest analysis identified specific microbes as potential predictors of diabetes and obesity in a city. Altogether, we generated the first Indian sewage microbiome and our non-invasive, high-throughput workflow could be emulated for future research, wastewater-based epidemiology and designing policies concerning public health.