Anti-Colorectal Cancer Effects of Inonotus hispidus (Bull.: Fr.) P. Karst. Spore Powder through Regulation of Gut Microbiota-Mediated JAK/STAT Signaling

Inonotus hispidus (Bull.: Fr.) P. Karst. spore powder (IHS) contains polyphenols and triterpenoids with pharmacological effects. Here, we analyzed its composition, and we investigated the effects of IHS on colorectal cancer (CRC) in B6/JGpt-Apc(em1Cin(min))/Gpt (Apc(Min/+)) mice and its potential mechanisms by analyzing gut microbiota and serum metabolomics. The enzyme-linked immunosorbent assays and Western blotting were used to confirm the changes in the cytokine and protein levels associated with IHS administration. The IHS affected the abundance of gut microbiota and the level of L-arginine (L-Arg). Furthermore, the IHS influenced T cells in Apc(Min/+) mice by increasing the interleukin (IL)-2 and decreasing the IL-5, -6, and -10 levels, thus suppressing tumor development. Overall, IHS showed anti-CRC properties in Apc(Min/+) mice by affecting the gut microbiota and serum metabolites, which in turn affected the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling, and regulated the abundance of CD8(+) T cells. These results provide experimental support for the potential future treatment of CRC with IHS.