Characterizing Gut Microbiome Composition, Activity, and Host Response in Global Populations

The human gut microbiome plays a central role in health, influencing metabolism, immune function, and susceptibility to chronic disease. However, most microbiome studies have focused on high-income populations, limiting our understanding of microbiome–host interactions across diverse global populations. Diet, lifestyle, and environmental exposures vary widely across populations, and these factors are thought to shape both microbial composition and functional activity, but few studies have directly measured active microbial functions outside of industrialized settings. To address these gaps, I reviewed computational analyses of global microbiome datasets, conducted experimental co-culture studies with human colonic epithelial cells, and profiled metatranscriptomic activity of fecal samples from industrialized and non-industrialized populations. Co-culture experiments revealed that urban-associated microbiomes preferentially activate innate immune pathways, and high-diversity microbiomes elicit stronger host transcriptional responses. Moreover, specific taxa, including Bifidobacterium adolescentis and Bacteroides dorei, correlate with lifestyle factors such as diet, and drive expression of specific host genes. Metatranscriptomic analyses demonstrate that microbial genomic abundance is not always predictive of transcriptional activity, and that transcriptionally active microbes differ across industrialized and non-industrialized populations. Together, these studies illuminate how lifestyle and industrialization shape gut microbial activity and host physiology across populations.