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. 2021 Jul 23;6(1):277.
doi: 10.1038/s41392-021-00600-9.

High stearic acid diet modulates gut microbiota and aggravates acute graft-versus-host disease

Bingyu Yang #  1   2 , Xianfeng Zhang #  3 , Huanle Gong #  1 , Yuhui Huang  4 , Chang Wang  5 , Haiyan Liu  6 , Chen Dong  7 , Shoubao Ma  8 , Xiaojin Wu  9 , Depei Wu  10
Affiliations

High stearic acid diet modulates gut microbiota and aggravates acute graft-versus-host disease

Bingyu Yang et al. Signal Transduct Target Ther. .
No abstract available

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Conflict of interest statement

The authors declare no competing interests.

Figures (VSports手机版)

Fig. 1
Fig. 1
High stearic acid diet (HSAD) modulates gut microbiota and aggravates acute graft-versus-host disease (aGVHD). a Survival of BALB/c recipient mice treated with normal diet (ND) or high stearic acid diet (HSAD) received bone marrow transplantation (BMT) from either syngeneic or allogeneic C57BL/6 donors. b Representative images and histopathological aGVHD scores for each aGVHD target organ on day 7 after allo-BMT, including skin, liver, lung, small intestine, and colon. Scale bars, 100 µm. c Survival of ND and HSAD recipients after allo-BMT treated with antibiotics (Abx) in drinking water. d Survival of ND and HSAD recipients after allo-BMT treated with fecal microbiota transplantation. e Taxonomic cladogram obtained from linear discriminant analysis effect size (LEfSe) showing bacterial taxa (phylum, class, and order) that were differentially abundant in HSAD and ND mice. Red indicates increased abundance in HSAD mice; green indicates increased abundance in ND mice. f Results of LEfSe analysis showing bacterial genus that were significantly different in abundance between HSAD and ND mice. g Survival after allo-BMT of ND mice receiving A. muciniphila and HSAD mice receiving B. fragilis compared to PBS vehicle. h Relative abundance of propionic acid, acetic acid, and butyric acid in feces of ND and HSAD mice (n = 8 per group). i Correlations of A. muciniphila levels with of stool metabolite levels, as determined by Spearman’s rank test. Red columns indicate significant positive correlations (Spearman’s correlation value r > 0.6, adjusted p < 0.05), and blue columns indicate significant negative correlations (r < −0.5, p < 0.05), except for succinic acid (p > 0.05). j Pie chart of seven representative SCFAs from bacterial cultures of A. muciniphila, each color represents one SCFA. k Levels of propionic acid, acetic acid, and butyric acid in bacterial culture supernatant and no-bacteria control. For j and k, n = 6 per group. l Survival after allo-BMT of HSAD recipients receiving donor cells in the absence of CD4+ T cells or CD8+ T cells. m Quantification of IL-17A+ Th17 and IFNγ+ Th1 lymphocytes in ND, HSAD, and antibiotic-treated HSAD (HSAD-Abx) recipients (n = 4–5 per group). n Quantification of IL-17A+ Th17 and IFNγ+ Th1 lymphocytes in ND mice, HSAD and ND mice receiving A. muciniphila (ND + A. muciniphila) recipients (n = 4–5 per group). o–q Lethally irradiated BALB/c ND and HSAD recipients were treated with WT B6 donors and IL-17A−/− B6 donors, IL-17F−/− B6 donors, and IFN-γ−/− B6 donors. Survival time was monitored. r Levels of IL-17A and IFN-γ were analyzed by ELISA between A. muciniphila supernatant and control co-cultured with stearic acid medium with different concentrations (0, 0.1, and 1 mM) under Th17- or Th1-stimulating conditions. s Secretion of IL-17A and IFN-γ from the supernatant of cultured naive CD4+ T cells under Th17- or Th1-stimulating conditions treated with various concentrations of acetate. For r and s, n = 2 per dose. t–u Quantification of A. muciniphila from the feces, and levels of acetate in the serum of non-aGVHD subjects (n = 13) and individuals with aGVHD (n = 12). v Correlations between the concentration of A. muciniphila in fecal samples and acetate in serum samples, as determined by Pearson’s rank test. Survival curves were compared using a log-rank (Mantel–Cox) statistical test. Comparisons between two groups were assessed using a two-tailed Student’s t test or Mann–Whitney U test. Multiple comparisons were evaluated statistically by two-way ANOVA, one-way ANOVA, or Kruskal–Wallis. Data are presented as the mean ± SEM. Exact p values are reported or presented as *p < 0.05, **p < 0.01, ***p < 0.001, or ****p < 0.0001
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