The herbal medicine ‘Indigo naturalis’ altered gut microbiota to accumulate IL-22+ ILC3s

Abstract Ulcerative colitis (UC) is a chronic inflammation of the large intestine led by the dysregulation of adaptive and innate immune responses. Recently, specific microbiota has been reported to instruct the immune cells and immune response. We have recently proved the clinical efficacy of “indigo naturalis (IN)”, a Chinese herbal medicine, on patients with UC by the multicenter randomized-controlled trial (INDIGO study, Gastroenterology 2018). 4%IN-fed mice ameliorated DSS-colitis (IN-DSS mice) compared to the normal diet-fed mice (ctrl-DSS mice). The number of IL-22+ ILC3s in the colonic lamina propria in IN-DSS mice increased more than the one in ctrl-DSS mice. We also confirmed that IN-fed diet mice significantly altered gut microbiota composition compared to the normal diet-fed mice. We next inoculated feces obtained from IN-fed mice or normal diet-fed mice to antibiotic treated mice (IN-FMT mice, ctrl-FMT mice respectively). Interestingly, IN-FMT mice significantly restored the pathology of DSS-induced colitis than ctrl-FMT mice with increased number of IL-22+ ILC3s. We showed IN induced specific microbiota which accumulated IL-22+ ILC3s in gut.