Exploring the influences of geographical variation on sequence signatures in the human gut microbiome

Geography shapes the structure and function of human gut microbiomes. In this study, we have explored the available human gut microbiome 16S rRNA sequence datasets of cohorts representing large geographical gradients. The 16S rRNA sequences representing V3-V4 as well as V4 regions generated using Illumina sequencing chemistry in the MiSeq platform encompassing the United States of America, Chile, South Africa, Kuwait, and Malaysia were subjected to in-depth computational biology analyses. Firmicutes and Bacteroidetes were the most dominant phyla present in all studied cohorts but Actinobacteria was exclusively present in high abundance in cohorts from Malaysia (15.99%). The relative abundance of five families, namely Bacteroidaceae, Ruminococcaceae, Prevotellaceae, Clostridiaceae, and Eubacteriaceae were highest representing the studied cohorts. The permutational multivariate analysis of variance (PERMANOVA) showed that the dissimilarity in the gut microbiome structure of cohorts representing studied countries was significant (R² = 0.28, P < 0.001). The calculated Firmicutes to Bacteroidetes (F : B) ratio was found to be lowest in cohorts from South Africa (1.11) and Chile (0.95). The cohorts from South Africa exhibited the highest alpha diversity based on Hill numbers at q=0, whereas at q=1 and 2, cohorts from Malaysia had the highest alpha diversity. The beta diversity analysis revealed that cohorts from Chile formed a distinct cluster among all the studied geographical locations. For the first time, the study also showed that cohorts from Malaysia representing short geographical distances exhibited distinct intrapopulation differences in the gut microbiome and may not be influenced by cultural and genetic factors.