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Metagenomics reveals impact of geography and acute diarrheal disease on the Central Indian human gut microbiome.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.
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Microbiomes in physiology: Insights into 21st century global medical challengesNew findings: What is the topic of this review? This review summarises the role of the gut microbiome in physiology and how it can be targeted as an effective strategy against two of the most important global medical challenges of our time namely, metabolic diseases and antibacterial resistance. What advances does it highlight? We outline the critical roles of the microbiome in regulating host physiology and discuss how microbiome analysis is useful for disease stratification to enable informed clinical decisions and develop interventions such as faecal microbiota transplantation (FMT), prebiotics, and probiotics. We also discuss the limitations of microbiome modulation, including the potential for probiotics to enhance antimicrobial resistance gene reservoirs, and that currently a "healthy microbiome" that can be used as a biobank for transplantation is yet to be defined. Abstract: The human gut microbiome plays a key factor in the development of metabolic diseases and antimicrobial resistance which are among the greatest global medical challenges of the 21st century. The symposium aimed to highlight state-of-the-art evidence for the role of the gut microbiome in physiology, from childhood to adulthood, and the impact this has on global disease outcomes, ageing and antimicrobial resistance. Although the gut microbiome is established early in life, over time the microbiome and their components including metabolites can become perturbed due to changes such as dietary habits, use of antibiotics and age. As gut microbial metabolites, including short chain fatty acids (SCFAs), secondary bile acids and trimethylamine-N-Oxide (TMAO), can interact with host receptors including G protein coupled receptors (GPCRs), and can alter host metabolic fluxes, they can significantly affect physiological homeostasis leading to metabolic diseases. These metabolites can be used to stratify disease phenotypes such as irritable bowel syndrome (IBS) and adverse events after heart failure and provide informed decisions on clinical management and treatment. While strategies such as probiotics, prebiotics, and faecal microbiota transplantation (FMT) have been proposed as interventions to treat and prevent metabolic diseases and antimicrobial resistance, caution must be exercised; first due to the potential of probiotics to enhance antimicrobial resistance gene reservoirs and second, a "healthy gut microbiome" that can be used as a biobank for transplantation is yet to be defined. We highlight that sampling other parts of the GI tract may produce more representative data than the faecal microbiome alone. This article is protected by copyright. All rights reserved.
