Industrialization drives convergent microbial and physiological shifts in the human metaorganism.

Understanding how host lifestyle and industrialization shape the human gut microbiome and intestinal physiology requires multimodal analyses across diverse global host contexts. Here, we generate multivariate data from the Global Microbiome Conservancy cohort, including gut microbiome, IgA-sequencing, host genotyping, diet, lifestyle and fecal biomarker profiles, to investigate host-microbiome interactions across gradients of industrialization and geography. We show that industrialization is associated with homogenized microbial compositions, reduced microbial diversity, and lower community stability, independent of host confounders. We further show that industrialization is linked to elevated markers of gut stress, increased IgA secretion, and altered patterns of IgA-bacteria interactions. Finally, we show that microbiome-based disease predictors trained on industrialized populations lose accuracy in less industrialized cohorts, highlighting limited cross-population transferability. Together, our results suggest profound restructuring of host-microbiome interactions due to industrialized lifestyles, and emphasize the need for inclusive, globally representative data to improve translational microbiome applications across diverse human populations.