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Metagenomic Study Tracks Gut Microbe Restoration After Antibiotics

NEW YORK (GenomeWeb) – Gut microbial communities appear capable of rebounding relatively quickly after a few days of treatment with broad-spectrum antibiotics, according to new research, though certain, subtle changes related to the antibiotic resistance potential of these communities remain.

"Despite a mild yet long-lasting imprint following antibiotics exposure, the gut microbiota of healthy young adults are resilient to a short-term, broad-spectrum antibiotics intervention, and their antibiotics resistance gene carriage modulates their recovery processes," University of Copenhagen researchers Oluf Pedersen, Manimozhiyan Arumugam, and Filip Knop, the study's co-corresponding and senior authors and their co-authors wrote in a study published in Nature Microbiology yesterday.

The researchers focused on a dozen healthy individuals with European ancestry, ranging in age from 18 to 40 years old, who were treated with broad spectrum antibiotics "of last resort" — meropenem, vancomycin, and gentamicin — for four days. Using metagenomic sequencing, they profiled gut microbial operational taxonomic units in stool samples collected before treatment, upon treatment completion, and again at four days, one months, and roughly six months after treatment.

Although they saw a short-term rise in potentially pathogenic bacteria such as Enterococcus faecalis or Fusobacterium nucleatum, coupled with a dip in Bifidobacterium bacteria and bacteria producing the short-chain fatty acid butyrate, the investigators noted that the participants' gut microbiomes typically bounced back within about a month and a half. Even so, a few stubborn bugs took longer to return, they noted, while certain microbes containing certain antibiotic resistance genes (ARGs) remained post-treatment.

Past studies have identified varied and shifting collections of ARGs in the human gut, the authors explained, reflecting antibiotic exposures through everything from food to clinical treatments. Even so, they wrote, "only a few studies have characterized the effects of particular antibiotic regimens on the gut ecosystems of individuals with respect to the associated resistomes."

To that end, the researchers used Illumina HiSeq 2000 metagenomic paired-end sequence data from 57 fecal samples collected from the study's 12 volunteer participants to trace the gut microbial diversity and metagenomic OTU profiles at the pre- and post-treatment time points.

In the first few days after meropenem, vancomycin, and gentamicin treatment, for example, the team saw a significant drop in representation by 50 microbial species, coupled with an increase in E. faecalis, F. nucleatum, Escherichia coli, and other species. Most of those patterns reverted within 38 days of treatment, but levels of Clostridium bolteae remained significantly higher and other baseline bugs did not reappear even after several months.

When the study authors dug into potential roles for ARGs in gut microbe recovery using the metagenomic sequence, available information from drug resistance databases, and multidrug efflux pump gene quantification, they saw signs that "resilience/recovery patterns of the individual species are modulated by ARG carriage."

While the treatment appeared to select for microbes containing beta-lactam resistance genes, for example, the broader antibiotic resistance gene profiles also seemed to influence the types of microbes that remained or returned post-treatment.

"Further studies are needed to verify whether the human gut microbiota is likewise resilient to multiple antibiotic exposures over prolonged periods and whether these results hold in children with an immature gut microbiota or in elderly people with an age-related decline immune competence and perturbed intestinal microbiota," the authors concluded.