Metagenome-wide association analysis identifies microbial determinants of post-antibiotic ecological recovery in the gut.

Autor: Chng KR; Genome Institute of Singapore, Singapore, Singapore., Ghosh TS; Genome Institute of Singapore, Singapore, Singapore.; APC Microbiome Ireland, University College Cork, Cork, Ireland., Tan YH; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Nandi T; Genome Institute of Singapore, Singapore, Singapore., Lee IR; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Ng AHQ; Genome Institute of Singapore, Singapore, Singapore., Li C; Genome Institute of Singapore, Singapore, Singapore., Ravikrishnan A; Genome Institute of Singapore, Singapore, Singapore., Lim KM; Genome Institute of Singapore, Singapore, Singapore., Lye D; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; National Centre for Infectious Disease, Singapore, Singapore.; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.; Tan Tock Seng Hospital, Singapore, Singapore., Barkham T; Tan Tock Seng Hospital, Singapore, Singapore., Raman K; Department of Biotechnology, Bhupat and Jyoti Mehta School of Biological Sciences, Indian Institute of Technology (IIT) Madras, Chennai, India.; Initiative for Biological Systems Engineering, IIT Madras, Chennai, India.; Robert Bosch Centre for Data Science and Artificial Intelligence (RBC-DSAI), IIT Madras, Chennai, India., Chen SL; Genome Institute of Singapore, Singapore, Singapore., Chai L; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Division of Infectious Diseases, University Medicine Cluster, National University Health System, Singapore, Singapore., Young B; National Centre for Infectious Disease, Singapore, Singapore. barnaby_young@ttsh.com.sg.; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore. barnaby_young@ttsh.com.sg.; Tan Tock Seng Hospital, Singapore, Singapore. barnaby_young@ttsh.com.sg., Gan YH; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. bchganyh@nus.edu.sg., Nagarajan N; Genome Institute of Singapore, Singapore, Singapore. nagarajann@gis.a-star.edu.sg.; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. nagarajann@gis.a-star.edu.sg.
Jazyk: angličtina
Zdroj: Nature ecology & evolution [Nat Ecol Evol] 2020 Sep; Vol. 4 (9), pp. 1256-1267. Date of Electronic Publication: 2020 Jul 06.
DOI: 10.1038/s41559-020-1236-0
Abstrakt: 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.
Databáze: MEDLINE