Gut resistome modulates resilience and recovery of gut microbiota after broad-spectrum antibiotic treatment. Antibiotic

Antibiotics have profound impacts on the microbial communities living in the human gut, where bacterial species harbor and exchange antibiotic resistance genes collectively called resistome. Human population surveys have demonstrated that gut microbial resistomes reflect local antibiotics usage patterns, while previous small cohort studies based on single antibiotic exposures have shown varying degrees of antibiotic impact on the gut microbiota and their associated resistome. However, the role of resistomes of particular gut species in their ability to persist in the face of antibiotic treatment has not been systematically studied.Applying shotgun sequencing and quantitative metagenomics, we analyzed the partial eradication and subsequent regrowth of gut microbiota in 12 healthy young men over a 6 month period following a 4-day intervention with three broad-spectrum antibiotics. The gut microbial communities of the study subjects underwent profound compositional changes due to the treatment but slowly recovered to near-baseline compositions. Immediately after the treatment, the gut microbiota featured an increased relative abundance of opportunistic and proinflammatory bacterial species, and a decreased relative abundance of short chain fatty acid producers, while exhibiting an increased functional potential for multidrug efflux pumps and virulence factors. These enrichment trends were weaker after 8 days and mostly cleared out after 42 days. However, 9 common intestinal commensal species found at baseline and associated with short chain fatty production or efficient digestion of polysaccharides remained undetectable in most of the subjects even after 180 days.Carrying genes that confer resistance to the antibiotics used in this multidrug study had specific consequences for the survival and de novo colonization potential of microbial species. While species harboring beta-lactam resistance genes were positively selected during and after the intervention, those harboring glycopeptide or aminoglycoside resistance exhibited increased odds of de novo colonization but decreased odds of survival. Despite a mild long-lasting imprint following exposure to three antibiotics, the gut microbiota of healthy young adults are resilient to a broad-spectrum antibiotic intervention, and their recovery process is modulated by antibiotic resistance gene carriage.