Abstract
The influence of gut fungi in chronic colitis was investigated by repeated oral administration ofCandida albicansin a 3% dextran sulfate solution (DSS) induced-colitis mouse model.Candidaadministration in the DSS (DSS+Candida) model enhanced the mortality rate and induced bacteremia (without candidemia) resulting from a gut perm-selectivity defect despite similar diarrheal severity in mice treated with DSS alone. The dominant fecal bacteria in DSS+Candidaand DSS alone mice werePseudomonasspp. andEnterobacterspp., respectively, implying thatCandidainduced gut dysbiosis. Interestingly, chloramphenicol-resistant bacterial colonies, predominantlyPseudomonasspp., appeared in the feces and blood of DSS+Candidamice (not the DSS alone group) during fungal culture. These antibiotic-resistant bacteria were also isolated,ex vivo, by incubating mouse feces with DSS and heat-killedCandidaor (1 -> 3)-beta-D-glucan, suggesting bacterial fermentation on fungi. Administration ofPseudomonas aeruginosaisolated from chloramphenicol-resistant bacteria in the DSS+Candidamodel enhanced the severity of disease, and increased growth of isolatedP aeruginosain blood agar containing heat-killedCandidawas demonstrated. These data suggested the selection of a highly virulent bacterial strain following fecalCandidapresentation in the gut. Additionally, reduction of fecal fungi with fluconazole decreased the burden of chloramphenicol-resistant bacteria, attenuating the severity of DSS+Candida. In conclusion, gutCandidainduced bacteremia in the DSS model through an inflammation-induced gut perm-selectivity defect and facilitated the growth of some gut bacteria. Treatment strategies aimed at reducing gut fungi could attenuate disease severity. Further investigation of gut fungi in inflammatory bowel disease is warranted.
