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1 Histological score linical Score Weight loss (%) olon length (cm) Supplementary figure (related to fig ) N ### ## ays on % E ### N ays on % $$ $$ # ## N. N N Supplementary figure : Lack of fibre in diet aggravates the development of colitis while high fibre and normal chow are protective -. linical score (), weight loss (), colon length () and histological score () were determined in mice fed on (n= mice), normal chow (N, n= mice) and diets (n= mice) for one week prior to days treatment with %. E. Representative H&E stained colonic sections of the mice fed on N, and prior and during days treatment with %. The results are shown as mean ± s.e.m and the experiment has been repeated twice. With p<., p<., p<. determined as group effect by NOV, # p<., ## p<., ### p<., p<. comparing N vs and $$ p<. comparing N to by Tukey s multiple comparison analysis, and p=., p<., p<. and p<. determined by t-test. Scale bar = m.

2 olon length (cm) Histological score Serum acetate concentration (mm) linical score Weight loss (%) Supplementary figure (related to fig ) 7 ays on the diet ays on % E ays on % # p=. F HO HO HO Supplementary figure : Lack of fibre in diet aggravates the development of colitis while diet enriched in resistant starch is protective. Serum acetate measured in serum of n= pooled mice fed on or resistant starch () diets for 7 and days. -E. linical score (), weight loss (), colon length () and histological score (E) were determined in mice fed on (n=) and (n=) for one week prior and during days treatment with %. F. Representative H&E stained colonic sections of the mice fed on and prior and during treatment with HO or %. The results are shown as mean ± s.e.m and the experiment has been repeated twice. The results are shown as mean±sem and the experiment has been repeated twice.. With p<., p=., p<. determined as group effect by NOV, # p<., p<. by onferroni s multiple comparison analysis and p<., p<. and p<. determined by t-test. Scale bar = m.

3 Weight loss (%) Weight loss (%) Supplementary figure (related to fig ) ays on % Gpr -/- Gpr -/ Gpr -/- - Gpr -/- - ays on % Gpr9 -/- Gpr9 -/- - - Gpr9 -/- - Gpr9 -/- - Supplementary figure : GPR and GPR9 are involved in the protective effect of high fibre diet from colitis,. Weight loss was determined in Gpr -/- () and in Gpr9 -/- () mice either fed on or on diets for a week prior to days of treatment with %.,. Representative H&E stained colonic in untreated Gpr -/- () and in Gpr9 -/- mice () fed on or on diet. The results are shown as mean ± s.e.m of n= mice per group and the experiment repeated twice. With p<., p<. and p<. determined by t-test. Scale bar = m.

4 olon length (cm) Histological score Supplementary figure (related to fig ) p=.7 LM into Gpr -/- LM into Gpr -/- water LM into Gpr -/- water LM into Gpr -/- LM into Gpr -/- Gpr -/- M into L water Gpr -/- M into L Gpr -/- M into L water Gpr -/- M into L Gpr -/- M into Gpr -/- - LM into L LM into Gpr -/- LM into Gpr -/- LM into Gpr -/- Gpr -/- M into L Gpr -/- M into L LM into L Gpr -/- M into Gpr -/- Gpr -/- M into L Gpr -/- M into L Supplementary figure : Expression of GPR in the non-hematopoietic compartment is necessary for the beneficial effects of high-fibre feeding in the colitis model.. olon length, and. histological score were determined in irradiated Gpr -/- mice reconstituted with bone marrow (M) cells (LM into Gpr -/- ) fed on (n=) or on (n=) diet, in irradiated mice reconstituted with Gpr -/- M cells (Gpr -/- M into L) fed (n=) or on diet (n=), in irradiated mice reconstituted with M cells (LM into L) fed on (n=) and in irradiated Gpr -/- mice reconstituted with Gpr -/- M cells (Gpr -/- M into Gpr -/- ) fed (n=) for a week and during the days treatment with % or water.. Representative H&E stained colonic sections of high-fibre fed irradiated Gpr -/- mice reconstituted with bone marrow cells (LM into Gpr -/- ), zero-fibre fed irradiated Gpr -/- mice reconstituted with bone marrow cells (LM into Gpr - /- ), high fibre fed mice reconstituted with Gpr -/- bone marrow cells (Gpr -/- M into L ) and zero fibre fed mice reconstituted with Gpr -/- bone marrow cells (Gpr -/- M into L ) treated with water. The results are shown as mean ± s.e.m. With p=.7, p<. p<., p<. and p<. determined by t-test. Scale bar = m.

5 linical score olon length (cm) Histological score Supplementary figure (related to fig ) Gpr9 -/- M into L Gpr9 -/- M into L ays on % HO -HO - -HO Supplementary figure : Expression of GPR9 in the hematopoietic compartment is not necessary for the beneficial effects of high-fibre feeding in colitis -. linical score (), colon length () and histological score () of irradiated mice reconstituted with Gpr9 -/- bone marrow (M) cells fed on (Gpr9 -/- M into L), or on (Gpr9 -/- M into L ) diets for a week prior to days treatment with %.. Representative H&E stained colonic sections fed mice reconstituted with Gpr9 -/- M cells and fed mice reconstituted with Gpr9 -/- M cells () treated with % for days a week after the start of the diet. The results are shown as mean ± s.e.m of n= mice in water groups and n= mice in treated groups. With p<. determined as group effect by NOV, p<. by Tukey s multiple comparison analysis and with p<., p<. determined by t-test. Scale bar = m.

6 olon length (cm) Supplementary figure (related to fig ) Nlrp -/- Nlrp -/- Nlrp -/- Supplementary figure : Expression of NLRP is not necessary for the beneficial effects of high fibre feeding in colitis. Representative H&E stained colonic sections of and Nlrp -/- mice fed on and prior to treatment with %.. olon length measured from mice fed on or on diets and from Nlrp -/- mice fed on or on diets prior to days treatment on %. The results are shown as mean ± s.e.m of n= mice per group. With p<. and p<. as determined by t-test. Scale bar = m.

7 verage clinical sore linical score Percent weight change Number of tumors per colon Tumor size (mm) model Supplementary figure 7 (related to fig ) tumor number (total) publication polyp size I dr Gpr -/- 7 ay Gpr -/- Gpr -/- E () (LF) Gpr -/- Gpr -/- Gpr -/- () Gpr -/- (LF) Supplementary figure 7. High fibre feeding protects from colon cancer through GPR. Weight loss measurement in (n= mice) and in Gpr -/- mice (n= mice) injected once with OM (at day ) prior to three rounds of.% for days (as indicated), with weeks recovery in between. -. Number () and diameter () of macroscopic polyps () determined at the endpoint. E. ancer clinical score in and in Gpr -/- mice fed on or diets. Results are shown as the mean ± s.e.m. With p<. determined by two-way NOV as a group effect and p<., p <., p<. as determined by t-test.

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