Relative enrichment of oral bacteria in feces indicates loss of intestinal commensals with implications for host health

Abstract High relative abundance of oral bacteria in the gut is considered abnormal and has been linked to intestinal disorders. However, this reported association has two alternate explanations: ectopic oral bacteria may increase in absolute numbers in the intestine and drive disease (the driver hypothesis) or, instead, intestinal commensals may decrease in absolute numbers and the relative rise in oral bacteria is simply an indicator of this loss (the marker hypothesis). Here we use experiments in mice and clinical data from patients to provide evidence in favor of the marker hypothesis. We demonstrate that depletion of intestinal bacteria by antibiotics increases the relative abundance of oral bacteria in the host feces without increasing their absolute abundance, and the relative enrichment can indicate host health parameters such as stool consistency, pathogen overgrowth, and immunity. Our results reframe the conventional interpretation of microbiome sequencing data with implications for intestinal disorders and microbiome therapies.