Consistently, in Gpr15+/+ mice, prolonged cigarette smoke exposure in the TNBS model led to aggravated colitis, as reflected by greater weight loss, elevated DAI, colon shortening, and worsened histological and endoscopic scores, accompanied by increased Gpr15 expression (Supplementary Fig. 3a, c, e, g). Here, GPR15 is linked to colitis.