A highly conserved and globally prevalent cryptic plasmid is among the most numerous mobile genetic elements in the human gut

Plasmids are extrachromosomal genetic elements that often encode fitness-enhancing features, yet many bacteria carry ‘cryptic’ plasmids with no clear benefit. We identified a cryptic plasmid, pBI143, that is ubiquitous across industrialized human gut microbiomes and, by copy number, is on average 14 times more numerous than crAssphage, previously considered the most abundant genetic element in the human gut. Mutations in pBI143 predominantly accumulate at specific positions across thousands of metagenomes, indicating strong purifying selection. pBI143 is typically monoclonal within individuals, likely due to priority effects and often vertically acquired from the mother. pBI143 transfers between Bacteroidales species and, while not measurably affecting host fitness in vivo, can transiently acquire additional genes. We demonstrate practical applications of pBI143, including sensitive detection of human fecal contamination and potential use as a cost-effective biomarker for colonic inflammatory states.