Geographical Context Shapes the Relationship Between Body Mass Index and the Human Gut Microbiome

The rapidly increasing prevalence of elevated body mass index (BMI) is a major public health crisis due to its association with the development of chronic metabolic disorders. While high caloric intake is a well-established contributor to high BMI, the gut microbiome is also known to contribute to the development of overweight and obesity and to their associated metabolic dysfunction. Previous studies have found that high BMI is associated with altered gut microbiome composition, reduced microbial diversity, and changes in predicted functional profiles, collectively contributing to gut dysbiosis. However, it remains unclear if such changes in the gut microbiome are consistent across different countries. This study investigated the effects of geographical location on the relationship between BMI and the human gut microbiome. To accomplish this, we analyzed three publicly available datasets consisting of 16S rRNA gene sequences from fecal samples collected across Argentina, Canada, Colombia, Scotland, Spain, and the United States. Our findings show that Shannon diversity and Faith’s phylogenetic diversity were negatively associated with BMI in the United States, while Faith’s phylogenetic diversity was negatively associated with BMI in Colombia. Gut microbial beta diversity only differed across groups in Colombia. At the taxonomic level, consistent BMI-associated shifts were most apparent at the genus level in all countries, although the magnitude of such changes varied by country. Finally, the predicted functional profile of the gut microbiome was primarily shaped by country, with some significant BMI-pathway correlations present in the United States. Together, these findings suggest that the relationship between BMI and the gut microbiome may be shaped by geographical contexts.