Changes in the composition of intestinal fungi and their role in mice with dextran sulfate sodium-induced colitis

TLDR

Intestinal fungi are increasingly recognized as key modulators of gut health, yet their influence on intestinal inflammation and bacterial composition remains poorly understood. Pyrosequencing showed that fungal communities vary by intestinal segment and location and shift dramatically during DSS‑induced colitis, with specific taxa such as Penicillium, Wickerhamomyces, Alternaria, and Candida rising while Cryptococcus, Phialemonium, Wallemia, and an unidentified Saccharomycetales genus fall; fungi‑depleted mice experienced aggravated acute colitis associated with bacterial dysbiosis, whereas bacteria‑depleted mice had attenuated disease, and chronic colitis correlated with elevated plasma (1,3)-β‑D‑glucan and fungal translocation, underscoring fungi’s protective role in acute inflammation but potential harm in chronic disease.

Abstract

Abstract Intestinal fungi are increasingly believed to greatly influence gut health. However, the effects of fungi on intestinal inflammation and on gut bacterial constitution are not clear. Here, based on pyrosequencing method, we reveal that fungal compositions vary in different intestinal segments (ileum, cecum and colon), prefer different colonization locations (mucosa and feces) and are remarkably changed during intestinal inflammation in dextran sulfate sodium (DSS)-colitis mouse models compare to normal controls: Penicillium, Wickerhamomyces, Alternaria, and Candida are increased while Cryptococcus, Phialemonium, Wallemia and an unidentified Saccharomycetales genus are decreased in the guts of DSS-colitis mice. Fungi-depleted mice exhibited aggravated acute DSS-colitis associated with gain of Hallella , Barnesiella , Bacteroides , Alistipes , and Lactobacillus and loss of butyrate-producing Clostridium XIVa and Anaerostipes compare with normal control. In contrast, bacteria-depleted mice show attenuated acute DSS-colitis. Mice with severely chronic recurrent DSS-colitis show increased plasma (1,3)-β-D-glucan level and fungal translocation into the colonic mucosa, mesenteric lymph nodes and spleen. This work demonstrate the different roles of fungi in acute and chronic recurrent colitis: They are important counterbalance to bacteria in maintaining intestinal micro-ecological homeostasis and health in acutely inflamed intestines, but can harmfully translocate into abnormal sites and could aggravate disease severity in chronic recurrent colitis.