Characterization of gut microbiomes in rural Honduras reveals novel species and associations with human genetic variation

The gut microbiome is integral to human health, yet research data to date has emphasized industrialized populations. Here, we performed large-scale shotgun metagenomic sequencing on 1,889 individuals from rural Honduras, providing the most comprehensive microbiome dataset from Central America. We identify a distinct microbial composition enriched in Prevotella species, with 861 previously unreported bacterial species. Functional profiling reveals unique carbohydrate metabolism adaptations consistent with high-fiber diets. Longitudinal analysis over two years reveals microbiome instability, with shifts in taxonomic diversity and metabolic potential, including changes associated with SARS-CoV-2 infection. Additionally, we characterize the gut virome and eukaryotic microbiome, identifying novel viral taxa, including Crassvirales phages, and a high prevalence of Blastocystis species in individuals with greater microbial diversity. Finally, by integrating host genomic data obtained from low-pass saliva whole-genome sequencing, we uncover significant host-microbiome associations, highlighting the influence of human genetic variation on microbial composition. People who are more genetically similar also have more similar gut microbiomes. These findings expand our understanding of microbiome diversity in non-industrialized populations, highlighting the uniqueness of those microbiomes and underscoring the need for global microbiome research.