Reconstruction of ancient microbial genomes from the human gut

Loss of gut microbial diversity in industrial populations is associated with chronic diseases, underscoring the importance of studying our ancestral gut microbiome. However, relatively little is known about the composition of pre-industrial gut microbiomes. In this study, we performed the first large-scale de novo assembly of microbial genomes from paleofeces. From eight authenticated human paleofeces (1,000-2,000 years old) with well-preserved DNA from the Southwestern U.S. and Mexico, we reconstructed 498 medium- and high-quality microbial genomes. Among the 181 genomes with the strongest evidence of being ancient and of human gut origin, 39% represent novel species-level genome bins. Tip dating suggests an approximate diversification timeline for the key human symbiont Methanobrevibacter smithii. Compared to 789 present-day human gut microbiome samples from eight countries, the paleofeces are more similar to non-industrialized than industrialized human gut microbiomes. Functional profiling of the paleofeces reveals significantly lower abundance of antibiotic resistance and mucin-degrading genes, as well as enrichment of mobile genetic elements relative to industrial gut microbiomes. This work opens the door to discovering and characterizing novel gut microbes from ancient microbiomes and interrogating the evolutionary history of the human gut microbiota through genome reconstruction from paleofeces.