Background: The Central Indian gut microbiome remains grossly understudied. Herein, we sought to investigate the burden of antimicrobial resistance and diarrheal diseases, particularly Clostridioides difficile, in rural-agricultural and urban populations in Central India, where there is widespread unregulated antibiotic use. We utilized shotgun metagenomics to comprehensively characterize the bacterial and viral fractions of the gut microbiome and their encoded functions in 105 participants. Results: We observed distinct rural-urban differences in bacterial and viral populations, with geography exhibiting a greater influence than diarrheal status. Clostridioides difficile disease was more commonly observed in urban subjects, and their microbiomes were enriched in metabolic pathways relating to the metabolism of industrial compounds and genes encoding resistance to 3 rd generation cephalosporins and carbapenems. By linking phages present in the microbiome to their bacterial hosts through CRISPR spacers, phage variation could be directly related to shifts in bacterial populations, with the auxiliary metabolic potential of rural-associated phages enriched for carbon and amino acid energy metabolism. Conclusions: We report distinct differences in antimicrobial resistance gene profiles, enrichment of metabolic pathways and phage composition between rural and urban populations, as well as a higher burden of Clostridioides difficile disease in the urban population. Our results reveal that geography is the key driver of variation in urban and rural Indian microbiomes, with acute diarrheal disease, including C. difficile disease exerting a lesser impact. Future studies will be required to understand the potential role of dietary, cultural, and genetic factors in contributing to microbiome differences between rural and urban populations.
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.
Background: Non-communicable diseases (NCDs) have become a major cause of morbidity and mortality in India. Perturbation of host–microbiome interactions may be a key mechanism by which lifestyle-related risk factors such as tobacco use, alcohol consumption, and physical inactivity may influence metabolic health. There is an urgent need to identify relevant dysmetabolic traits for predicting risk of metabolic disorders, such as diabetes, among susceptible Asian Indians where NCDs are a growing epidemic. Methods: Here, we report the first in-depth phenotypic study in which we prospectively enrolled 218 adults from urban and rural areas of Central India and used multiomic profiling to identify relationships between microbial taxa and circulating biomarkers of cardiometabolic risk. Assays included fecal microbiota analysis by 16S ribosomal RNA gene amplicon sequencing, quantification of serum short chain fatty acids by gas chromatography-mass spectrometry, and multiplex assaying of serum diabetic proteins, cytokines, chemokines, and multi-isotype antibodies. Sera was also analysed for N-glycans and immunoglobulin G Fc N-glycopeptides. Results: Multiple hallmarks of dysmetabolism were identified in urbanites and young overweight adults, the majority of whom did not have a known diagnosis of diabetes. Association analyses revealed several host–microbe and metabolic associations. Conclusions: Host–microbe and metabolic interactions are differentially shaped by body weight and geographic status in Central Indians. Further exploration of these links may help create a molecular-level map for estimating risk of developing metabolic disorders and designing early interventions.
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