Age-dependent patterns of the gut microbiome, antibiotic resistome, and pathogenicity in captive koalas (Phascolarctos cinereus)

Gut microbiome has a profound influence on koalas' health. Yet, the relationships among the gut bacteriome, virome, antibiotic resistome, and pathogenicity throughout different stages in koala's life remain elusive. Here, we presented a metagenome-resolved survey of gut microbiome utilizing 75 fecal samples from three groups of captive koalas. The diversity of bacteriome and virome were age-dependent, predominating in adult koalas. Lytic viruses increased with age as lysogenic viruses and bacterial hosts declined, and virus-to-microbe ratios rose, revealing concomitant age-related shifts in microbial communities, though causality remains unresolved. Antibiotic resistance genes (ARGs) were more prevalent in young koalas, unlike in humans, where they accumulate with age. Two ARG-carrying pathogens, Klebsiella pneumoniae and Escherichia coli, were identified and cultured, with K. pneumoniae and E. coli predominating in young koalas. One age-dependent lytic virus infecting K. pneumoniae only detected in young koalas, and two lysogenic viruses infecting E. coli identified the in young and adult koalas. Analyses showed a positive correlation between mobile genetic elements (MGEs) and virulence factors (VFs), which facilitated the widespread dissemination of VFs and impacted health. Collectively, this study advances the understanding of gut microbiome in health, providing solutions to the treatment and management of captive koalas.