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Ecological and Evolutionary responses to Antibiotic Treatment in the Human Gut Microbiota.

ABSTRACT: The potential for antibiotics to affect the ecology and evolution of the human gut microbiota is well recognised and has wide-ranging implications for host health. Here, we review the findings of key studies that surveyed the human gut microbiota during antibiotic treatment. We find several broad patterns including the loss of diversity, disturbance of community composition, suppression of bacteria in the Actinobacteria phylum, amplification of bacteria in the Bacteroidetes phylum, and promotion of antibiotic resistance. Such changes to the microbiota were often, but not always, recovered following the end of treatment. However, many studies reported unique and/or contradictory results, which highlights our inability to meaningfully predict or explain the effects of antibiotic treatment on the human gut microbiome. This problem arises from variation between existing studies in three major categories: differences in dose, class and combinations of antibiotic treatments used; differences in demographics, lifestyles, and locations of subjects; and differences in measurements, analyses and reporting styles used by researchers. To overcome this, we suggest two integrated approaches: (i) a top-down approach focused on building predictive models through large sample sizes, deep metagenomic sequencing, and effective collaboration; and (ii) a bottom-up reductionist approach focused on testing hypotheses using model systems.

SUBMITTER: Pennycook JH

PROVIDER: S-EPMC8498795 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Multidrug-resistant plasmid-carrying bacteria are of particular clinical concern as they could transfer antibiotic resistance genes to other bacterial species. However, little is known whether evolutionary adaptation of plasmid-carrying bacteria after long-term antibiotic exposure could affect their subsequent colonization of the human gut. Herein, we combined a long-term evolutionary model based on Escherichia coli K-12 MG1655 and the multidrug-resistant plasmid RP4 with in vivo colonization experiments in mice. We found that the evolutionary adaptation of plasmid-carrying bacteria to antibiotic exposure facilitated colonization of the murine gut and subsequent plasmid transfer to gut bacteria. The evolved plasmid-carrying bacteria exhibited phenotypic alterations, including multidrug resistance, enhanced bacterial growth and biofilm formation capability and decreased plasmid fitness cost, which might be jointly caused by chromosomal mutations (SNPs in rpoC, proQ, and hcaT) and transcriptional modifications. The upregulated transcriptional genes, e.g., type 1 fimbrial-protein pilus (fimA and fimH) and the surface adhesin gene (flu) were likely responsible for the enhanced biofilm-forming capacity. The gene tnaA that encodes a tryptophanase-catalyzing indole formation was transcriptionally upregulated, and increased indole products participated in facilitating the maximum population density of the evolved strains. Furthermore, several chromosomal genes encoding efflux pumps (acriflavine resistance proteins A and B (acrA, acrB), outer-membrane protein (tolC), multidrug-resistance protein (mdtM), and macrolide export proteins A and B (macA, macB)) were transcriptionally upregulated, while most plasmid-harboring genes (conjugal transfer protein (traF) and (trbB), replication protein gene (trfA), beta-lactamase TEM precursor (blaTEM), aminoglycoside 3'-phosphotransferase (aphA) and tetracycline resistance protein A (tetA)) were downregulated. Collectively, these findings demonstrated that evolutionary adaptation of plasmid-carrying bacteria in an antibiotic-influenced environment facilitated colonization of the murine gut by the bacteria and plasmids.

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Ecological and Evolutionary responses to Antibiotic Treatment in the Human Gut Microbiota.

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