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. Author manuscript; available in PMC: 2023 Nov 2.
Published in final edited form as: Nature. 2022 Nov 2;611(7936):578–584. doi: 10.1038/s41586-022-05380-y

Fig. 3 |. Microbiota-derived CA and host FXR mediate inulin fibre diet-triggered type 2 inflammation.

Fig. 3 |

a, The number of eosinophils in the colon. n = 3 mice. b, The frequency of colon eosinophils after administration of the diets (n = 8 (control) and n = 6 (inulin fibre) mice) or metabolites (n = 3 (CA + IPA), n = 4 (SCFAs or CA) and n = 5 (IPA) mice). c, The frequency of colon eosinophils. n = 4 mice. d, The frequency of IL-5-expressing ILC2s in the lungs. n = 4 (control or inulin fibre) and n = 3 (CA) mice. e, The frequency of IL-5-expressing ILC2s in naive mouse lung cell preparations after incubation in vitro under the indicated conditions. n = 4 mice. f, The frequency of IL-5-expressing ILC2s in PBMCs from human donors (n = 8 donors) co-cultured with the human colonic stromal cell line Ccd-18Co. g–i, Spatial transcriptomic analyses of distal colon tissues. g, A representative H&E-stained colon section, which was overlaid by ‘spots’ containing transcriptional information. h, Heat map showing the genes in each layer of the colon sections with uncorrected P < 0.01 (Wilcoxon rank-sum test). i, Spatial representation of the relative expression of FXR-encoding Nr1h4 in representative colon tissues. Scale bar, 500 μm. j, The frequency of colon and lung eosinophils in the bone marrow chimeric mice with indicated donor to recipient conditions. WT→WT: n = 3 (control mice) and n = 4 (inulin fibre) mice; irradiated Nr1h4−/− mice with WT bone marrow (WT→Nr1h4−/− (KO)): n = 4 mice; and irradiated WT mice with Nr1h4−/− bone marrow (KO→WT): n = 4 mice. k,l, Serum CA (k) and tissue eosinophil (l) levels in gnotobiotic mice with human microbiota. Each pair of dots represents the mean levels of all of the mice receiving microbiota from a single human donor. n = 4 donors. m, Schematic of the bile acid deconjugation pathway. n, The frequency of colon and lung eosinophils in GF mice monocolonized with WT or bsh-deleted B. ovatus (WT Bo or Δbsh Bo, respectively). n = 3 (Δbsh Bo control diet group) and n = 4 (other groups). Data are representative of (a, c–e, j and n) or pooled from (b and f) two independent experiments. Data are mean (k and l) or mean ± s.e.m. (a–f, j and n). Statistical analysis was performed using two-way ANOVA with uncorrected Fisher’s LSD test (a, j and n); one-way ANOVA with Dunnett’s multiple-comparisons test (b and d); unpaired (c) or paired (e, f, k and l) two-tailed t-tests; or pairwise Wilcoxon test with Bonferroni correction (i).