Abstract
Despite extensive research on the gut microbiome of healthy individuals from a single country, there are still a limited number of population-level comparative studies. Moreover, the sequencing approach used in most related studies involves 16 S ribosomal RNA (rRNA) sequencing with a limited resolution, which cannot provide detailed functional profiles. In the present study, we applied a combined analysis approach to analyze whole metagenomic shotgun sequencing data from 2035 healthy adult samples from six countries across four continents. Analysis of core species revealed that 13 species were present in more than 90 % of all investigated individuals, the majority of which produced short-chain fatty acids (SCFA)-producing bacteria. Our analysis revealed consistently significant differences in gut microbial species and pathways between Western and non-Western countries, such as Escherichia coli and the relation of MetaCyc pathways to the TCA cycle. Specific changes in microbial species and pathways are potentially related to lifestyle and diet. Furthermore, we identified several noteworthy microbial species and pathways that exhibit distinct characteristics specific to China. Interestingly, we observed that China (CHN) was more similar to the United States (USA) and United Kingdom (GBR) in terms of the taxonomic and functional composition of the gut microbiome than India (IND) and Madagascar (MDG), which were more similar to the China (CHN) diet. The current study identified consistent microbial features associated with population and geography, which will inspire further clinical translations that consider paying attention to differences in microbiota backgrounds and confounding factors.