Dietary soyasaponin attenuates 2,4‐dinitrofluorobenzene‐induced contact hypersensitivity via gut microbiota in mice

Summary Soyasaponins (SSs) are abundant in soybeans and display inhibitory activity against contact hypersensitivity (CHS), which is often used as a mouse model for allergic contact dermatitis (ACD); however, their therapeutic mechanisms remain unknown. Here, we attempted to clarify the role of gut microbiota in the inhibition of CHS by dietary soyasaponins. For antibiotic treatment, mice were administered a mixture of ciprofloxacin and metronidazole or vancomycin. These antibiotics and SSs were given to mice via drinking water 3‐weeks prior to CHS induction with 2,4‐dinitrofluorobenzene, and the mice were analysed for ear swelling, tissue oedema, infiltration of Gr‐1‐positive immune cells, the composition of faecal microbiota and regulatory T (T reg ) cells. The soyasaponin diets attenuated ear swelling and tissue oedema, and reduced the number of Gr‐1‐positive cells infiltrating ear tissues. CHS caused changes in the structure of the gut microbiota, but dietary SSs blocked the changes in the microbiota composition. Ciprofloxacin and metronidazole treatments significantly enhanced the severity of CHS symptoms, whereas vancomycin treatment blocked the suppressive effect of dietary SSs on CHS. These antibiotic treatments differed in their effects on the gut microbiota composition. T reg cells in auricular lymph node and spleen increased under SS‐enriched diets, but this increase was blocked by vancomycin treatment. These results suggest that dietary SSs exert their inhibitory activity on CHS via the gut microbiota in mice, suggesting that dietary supplementation with SSs may have beneficial effects on ACD patients, but that the gut microbiota is a critical determinant of the therapeutic value of dietary SSs.