Opposing implications of co-evolutionary lineages and traits of gut microbiome on human health status

Abstract Little is known about the co-evolutionary history of the human gut microbe and its relevance to host physiology. Here, we constructed a gut prokaryotic genomic database of wild primates (pSGBs) and compared it with the human gut prokaryotic database (hSGBs) to define shared co-evolutionary clusters (SCEC-hSGBs) and co-evolutionary traits of hSGBs. We analyzed the evolutionary trends of specific functions like carbohydrate-active enzymes and antibiotic resistance in hSGBs and uncovered host-jumping events and genome reduction tendencies in SCEC-hSGBs. Intriguingly, the SCEC-hSGBs and the super enrichers of the traits (SUEN-hSGBs), which are putatively partially derived from carnivores, showed opposite implications for host health status. Specifically, SUEN-hSGBs are enriched in various diseases, showing a negative correlation with gut biodiversity and disproportionate contributions to the known health-negative marker taxa and metabolite. Our study provides insight into the origin and adaptability of human gut microbes and references for developing probiotics and microbiome-based host health prediction.