Fig. 3. D. newyorkensis prevents DSS-induced colitis by regulating CD25⁺Foxp3⁺ Tregs partially through the SCFA-GPR43 signaling axis.

a Heat map showing mRNA expression determined by bulk RNA-Seq in colon samples from vehicle (Veh)-treated (n = 3) or D. newyorkensis (Dub)-colonized wild-type C57BL/6J mice (n = 4) at D7 post-DSS treatment. b, c CD25⁺Foxp3⁺Tregs (b) and IL-17⁺ CD4⁺ T cells (c) in mesenteric lymph nodes (MLN) and colonic lamina propria (cLP) of conventional or Abx-treated WT mice colonized with Dub, A. muciniphila (Akk), or E. faecalis (EF) (n = 6) were examined by flow cytometry at D7 post-DSS treatment. d–f Conventional WT or Foxp3-DTR mice (n = 5) were colonized with 10⁹ CFU of Dub, Akk, or EF and subjected to DSS treatment. At D7 post-DSS administration, colon length measurement (d) and histopathological evaluation (e, f) were performed. g SCFA concentration in Dub, Akk, or EF culture supernatant determined by GC/MS (n = 4). h–m Conventional WT and Gpr43^−/− mice (n = 4) were colonized with Dub (10⁹ CFU) twice or administrated propionate (Prop) in drinking water for 3 weeks before DSS exposure. At D7 post-DSS administration, CD25⁺Foxp3⁺Tregs (h) and IL-17⁺ CD4⁺ T cells (i) in MLNs and cLP of conventional WT or Gpr43^−/− mice (n = 4) were quantified by flow cytometry. Meanwhile, colon length (j), histopathological score by HE staining (k, l) (n = 4), and expression of ZO-1, OCLN, and Muc2 in isolated colonic intestinal epithelial cells (cIECs) (WT, n = 4; Gpr43^−/−, n = 3) (m) was determined. Fold of change in frequencies of CD25⁺Foxp3⁺Tregs or IL-17⁺ CD4⁺ T cells (b, c, h, i), colon length (d), or SCFA concentrations (g) between groups was calculated and presented with numbers in red. Dashed lines at 1 indicate that the treatments have equal value as normalized controls. Results are representative of data generated in at least two independent experiments and are expressed as mean ± SEM, and 2-sided P-values were examined by the Student’s t-test. Source data are provided as a Source Data file.