In the meanwhile, the enhanced levels of GPR41 and GPR43 on the cell surface were observed in indigo naturalis-treated rats with DSS administration, indicating that GPR41/43 pathway was necessary for prevention against DSS-induced colitis by indigo naturalis, and indigo naturalis-induced microbiota alteration may be a key mediator for this effect through increased production of SCFAs, especially butyrate acid. The gene discussed is FFAR2; the disease is colitis.