A family of anti-Bacteroidales peptide toxins wide-spread in the human gut microbiota.
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ABSTRACT:
SUBMITTER: Coyne MJ
PROVIDER: S-EPMC6671954 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The bacterial composition of the human fecal microbiome is influenced by many lifestyle factors, notably diet. It is less clear, however, what role host genetics plays in dictating the composition of bacteria living in the gut. In this study, we examined the association of ~200K host genotypes with the relative abundance of fecal bacterial taxa in a founder population, the Hutterites, during two seasons (n = 91 summer, n = 93 winter, n = 57 individuals collected in both). These individuals live and eat communally, minimizing variation due to environmental exposures, including diet, which could potentially mask small genetic effects. Using a GWAS approach that takes into account the relatedness between subjects, we identified at least 8 bacterial taxa whose abundances were associated with single nucleotide polymorphisms in the host genome in each season (at genome-wide FDR of 20%). For example, we identified an association between a taxon known to affect obesity (genus Akkermansia) and a variant near PLD1, a gene previously associated with body mass index. Moreover, we replicate a previously reported association from a quantitative trait locus (QTL) mapping study of fecal microbiome abundance in mice (genus Lactococcus, rs3747113, P = 3.13 x 10-7). Finally, based on the significance distribution of the associated microbiome QTLs in our study with respect to chromatin accessibility profiles, we identified tissues in which host genetic variation may be acting to influence bacterial abundance in the gut.
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Project description:Background and objectivesSlowing the spread of antimicrobial resistance is urgent if we are to continue treating infectious diseases successfully. There is increasing evidence microbial interactions between and within species are significant drivers of resistance. On one hand, cross-protection by resistant genotypes can shelter susceptible microbes from the adverse effects of antibiotics, reducing the advantage of resistance. On the other hand, antibiotic-mediated killing of susceptible genotypes can alleviate competition and allow resistant strains to thrive (competitive release). Here, by observing interactions both within and between species in microbial communities sampled from humans, we investigate the potential role for cross-protection and competitive release in driving the spread of ampicillin resistance in the ubiquitous gut commensal and opportunistic pathogen Escherichia coli.MethodologyUsing anaerobic gut microcosms comprising E.coli embedded within gut microbiota sampled from humans, we tested for cross-protection and competitive release both within and between species in response to the clinically important beta-lactam antibiotic ampicillin.ResultsWhile cross-protection gave an advantage to antibiotic-susceptible E.coli in standard laboratory conditions (well-mixed LB medium), competitive release instead drove the spread of antibiotic-resistant E.coli in gut microcosms (ampicillin boosted growth of resistant bacteria in the presence of susceptible strains).Conclusions and implicationsCompetition between resistant strains and other members of the gut microbiota can restrict the spread of ampicillin resistance. If antibiotic therapy alleviates competition with resident microbes by killing susceptible strains, as here, microbiota-based interventions that restore competition could be a key for slowing the spread of resistance.Lay summarySlowing the spread of global antibiotic resistance is an urgent task. In this paper, we ask how interactions between microbial species drive the spread of resistance. We show that antibiotic killing of susceptible microbes can free up resources for resistant microbes and allow them to thrive. Therefore, we should consider microbes in light of their social interactions to understand the spread of resistance.
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