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It is known that the microbiome affects human physiology, emotion, disease, growth, and development. Most humans exhibit reduced appetites under high temperature and high humidity (HTHH) conditions, and HTHH environments favor fungal growth. Therefore, we hypothesized that the colonic mycobiota may affect the host’s appetite under HTHH conditions. Changes in humidity are also associated with autoimmune diseases. In the current study mice were fed in an HTHH environment (32°C ± 2°C, relative humidity 95%) maintained via an artificial climate box for 8 hours per day for 21 days. Food intake, the colonic fungal microbiome, the feces metabolome, and appetite regulators were monitored. Components of the interleukin 17 pathway were also examined. In the experimental groups food intake and body weight were reduced, and the colonic mycobiota and fecal metabolome were substantially altered compared to control groups maintained at 25°C ± 2°C and relative humidity 65%. The appetite-related proteins LEPT and POMC were upregulated in the hypothalamus (p < 0.05), and NYP gene expression was downregulated (p < 0.05). The expression levels of PYY and O-linked β-N-acetylglucosamine were altered in colonic tissues (p < 0.05), and interleukin 17 expression was upregulated in the colon. There was a strong correlation between colonic fungus and sugar metabolism. In fimo some metabolites of cholesterol, tromethamine, and cadaverine were significantly increased. There was significant elevation of the characteristic fungi Solicoccozyma aeria, and associated appetite suppression and interleukin 17 receptor signaling activation in some susceptible hosts, and disturbance of gut bacteria and fungi. The results indicate that the gut mycobiota plays an important role in the hypothalamus endocrine system with respect to appetite regulation via the gut-brain axis, and also plays an indispensable role in the stability of the gut microbiome and immunity. The mechanisms involved in these associations require extensive further studies.