Abstract
Background The impact of the rapid urbanisation of low- and middle-income countries on the human gut microbiome remains grossly understudied. Whilst the effect of urbanisation on the bacterial populations of the human gut microbiome have been documented, little is known about the influence of diet and antibiotics on the bacteriome, its virome, and antibiotic resistome. Here, we use shotgun metagenomics to comprehensively characterise the bacterial and viral fractions of the human gut microbiome, and their encoded functions, from two divergent Central Indian populations (rural agriculturalists from Melghat and an urban population in Nagpur). Additionally, we investigate cohorts with and without diarrhoea, and the potential burden of Clostridioides difficile, associated with widespread unregulated use of antibiotics in India. Results We observed distinct rural-urban differences in the gut microbiome, including viral diversity and composition, with geography exhibiting a greater influence than diarrhoeal status. Urban microbiomes were enriched in metabolic pathways responsible for degradation of drugs and organic compounds, which were predicted to relate to replacement of rural-enriched Prevotella spp. and fermentative Clostridiales with Enterobacteriaceae and Bacteroides spp. By linking phages present in the microbiome to their bacterial hosts through CRISPR spacers, a shift from Prevotella- and Eubacterium-infecting phages to Bacteroides- and Parabacteroides-infecting phages was observed in rural and urban populations, respectively. Additionally, the auxiliary metabolic potential of rural-associated phage populations was enriched for carbon and amino acid energy harvesting potential, compared to urban-associated phages. A core set of antimicrobial resistance genes was identified in both populations, particularly those conferring resistance to macrolides, tetracyclines and 1stgeneration cephalosporins, with the majority also showing evidence of resistance to fluoroquinolones, aminoglycosides and sulphonamides. In a subgroup of urban subjects with diarrhoea and high antibiotic exposure, most of whom tested positive for C. difficile toxin, evidence of resistance to fosfomycin, glycopeptides, daptomycin, 3rd generation cephalosporins and carbapenems was widespread. Conclusions We report distinct differences in antimicrobial resistance gene profiles as well as a marked variation in the burden of C. difficile disease between rural and urban populations. The key drivers of variation in urban and rural Indian microbiomes are geography, diet, industrial and healthcare exposures.
Metagenomics of Antimicrobial Resistance in Gut Microbiome