Dysbiosis and Enterobacteriaceae-associated accumulation of antimicrobial resistance in the gut bacterial reservoir of captive sloth bear (Melursus ursinus)

Captivity-associated conditions modulate the gut microbiota in wild animals as they are given several medications including antibiotics, and are exposed to various anthropogenic stressors throughout their captive lives. Our understanding of how these factors modify the gut microbiome, its resistome and associated mobilome is nascent at the very best. In this study, we analysed metagenomic data from 215 captive sloth bears from across India to describe their gut microbiota in association with age, gender, duration in captivity, health status, body condition, etc. Overall, we found low microbial diversity and evenness across sampled locations, along with dominance of select taxa like Streptococcus , Escherichia , Klebsiella , Sarcina and Clostridium . On the contrary, we observed a very diverse resistome, and almost all bears consistently showed high levels of multi-drug resistance, even when not treated recently with antibiotics. Abundances of WHO-priority pathogens such as Escherichia and Shigella positively correlated to higher antibiotic resistance gene (ARG) abundances and richness. We further observed that ARGs which confer multi-drug resistance mostly via efflux pump pathways, were associated with plasmids and other mobile genetic elements, increasing the risk of resistance dissemination. Metagenome-assembled genomes (MAGs) of Enterobacteriaceae species such as Escherichia spp. and Klebseilla spp . showed a disproportionately high accumulation of ARGs, further underscoring their virulence. In summary, our study highlights the importance of metagenomic studies to understand the effects of captivity on the gut health and accumulation of antimicrobial resistance in endangered animals.