Metagenome-wide association analysis identifies microbial determinants of post-antibiotic ecological recovery in the gut
Chng K, Ghosh T, Tan Y, Nandi T, Lee I, Ng A, Li C, Ravikrishnan A, Lim K, Lye D, Barkham T, Raman K, Chen S, Chai L, Young B, Gan Y, Nagarajan N (2020) Nature Ecology and Evolution doi: 10.1038/s41559-020-1236-0
Loss of diversity in the gut microbiome can persist for extended periods after antibiotic treatment, impacting microbiome function, antimicrobial resistance and probably host health. Despite widespread antibiotic use, our understanding of the species and metabolic functions contributing to gut microbiome recovery is limited.
Using data from 4 discovery cohorts in 3 continents comprising >500 microbiome profiles from 117 individuals, we identified 21 bacterial species exhibiting robust association with ecological recovery post antibiotic therapy.
Functional and growth-rate analysis showed that recovery is supported by enrichment in specific carbohydrate-degradation and energy-production pathways. Association rule mining on 782 microbiome profiles from the MEDUSA database enabled reconstruction of the gut microbial 'food web', identifying many recovery-associated bacteria as keystone species, with the ability to use host- and diet-derived energy sources, and support repopulation of other gut species.
Experiments in a mouse model recapitulated the ability of recovery-associated bacteria (Bacteroides thetaiotaomicron and Bifidobacterium adolescentis) to promote recovery with synergistic effects, providing a boost of two orders of magnitude to microbial abundance in early time points and faster maturation of microbial diversity.
The identification of specific species and metabolic functions promoting recovery opens up opportunities for rationally determining pre- and probiotic formulations offering protection from long-term consequences of frequent antibiotic usage.
FAB RESEARCH COMMENT:
Antibiotic use can cause prolonged disruption of the gut microbiome, with associated negative side-effects on health.
This study used data from human microbiome samples to identify particular species of gut microbes that might help to promote recovery of microbial balance and diversity after antibiotic use, and to investigate their metabolic functions. Those microbes were then investigated via animal studies, which supported their association with faster recovery of the microbiome following its disruption by antibiotics.
These findings may prove useful in the development of probiotics tailored to promote and support more rapid recovery of the gut microbiome following antibiotic use.
Among other consequences, antibiotic exposure in infancy has been linked with weight gain and obesity in later childhood (consistent with what has long been known from the use of antibiotics in animals) - see: