Yuta Kanai, Research Institute for Microbial Diseases, Osaka University

Yuta Kanai1, Tomohiro Kotaki1, Toshie Ishisaka1, Satoko Sakai1, Eriko Hirai1, Daisuke Motooka2, Takeshi Kobayashi1,3,4 1 Department of Virology, Research Institute for Microbial Diseases, Osaka University, Japan. 2 Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Japan. 3 Center for Infectious Disease Education and Research, Osaka University, Japan. 4 Center for Advanced Modalities and DDS, Osaka University, Japan.

Pathogenesis and Immunity

Rotavirus (RV) causes severe gastroenteritis in infants, with approximately 150,000 deaths recorded annually worldwide. Upon infection via the oral route, the RV passes through the stomach and upper intestine, which are filled with proteases, mucus, and bacteria. Intestinal microbiota plays a critical role in host immunity and pathogen interactions; however, its effects on enteric viral infections remain unclear. In this study, we investigated the influence of the gut microbiota on simian RV infection using a mouse model. Mice were treated with various antibiotics (cocktail or individual) via drinking water for two weeks before oral inoculation with the simian RV SA11 strain. RV infection was inhibited in mice treated with an antibiotic cocktail, with effects varying according to antibiotic class. β-lactam antibiotics alone were sufficient to abolish the infection. Germ-free mice exhibited strong resistance to RV infection. However, susceptibility was restored upon gut microbiota reconstitution via oral-fecal transplantation from normal mice. Metagenomic analysis revealed dynamic alterations in specific bacterial populations associated with infection susceptibility. These findings demonstrate that the intestinal microbiota composition critically influences simian RV infection in mice. Depending on the antibiotic species, variations in inhibition suggested that particular bacteria were involved in RV infection. Further characterization of the bacterial taxa may provide novel insights into microbiota-virus interactions and potential microbiome-based therapeutic strategies for enteric viral infections.