Figure 6.

Manipulation of gut microbiota protects from diabetes development in MyD88^−/−NY8.3 mice. (A) Diabetes incidence in MyD88^−/−NY8.3NOD mice after 4-wk-old MyD88^−/−NY8.3NOD mice were cohoused with an equal number and age- and sex-matched NOD mice. F, female; M, male. (B) Diabetes development of MyD88^−/−NY8.3NOD mice after fecal OT. The fresh gut bacteria (∼10⁸–10⁹ culturable bacteria/mouse) from diabetes-free cohoused MyD88^−/−NY8.3 mice (from A) were fed orally to sex-matched 4-wk-old naive MyD88^−/−NY8.3NOD mice. (C) Insulitis of MyD88^−/−NY8.3NOD mice after cohousing with WT NOD mice or OT (from A and B). More than120 islets from five to six treated mice/group were examined. Representative pancreatic sections are shown on the left, and the summary of the insulitis scores is shown on the right. χ² test was used for analysis. (D) α-Diversity of gut microbiota is shown by Chao richness. Fecal samples from the control, cohoused, and OT MyD88^−/−NY8.3NOD mice were used for taxonomic analysis by 16S rRNA sequencing. One- or two-tailed Mann-Whitney test was used for analysis. Data are shown as individual samples. (E) β-Diversity is shown. Assessment of the differences in the bacterial composition of the gut microbiota in the mice that were treated either by cohousing or OT (red or green symbols) compared with the control mice (blue symbols) is shown by principal component analysis (PCoA). ANOSIM was used for statistical analysis. (F and G) Comparison of the abundance of gut bacteria in the control, cohoused, and OT MyD88^−/−NY8.3NOD mice is shown by phylum (F) and family (G). Two-way ANOVA was performed with Bonferroni correction. (H) Diabetes incidence in the progeny of MyD88^−/−NY8.3NOD mice that were protected from diabetes after fecal OT (shown in B). (A, B, and G) The data were pooled from at least two independent experiments. (D–G) The results are from one of two independent experiments. Data are shown as mean ± SEM. **, P < 0.01; ***, P < 0.001.