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Microbial metabolite butyrate facilitates M2 macrophage polarization and function.

Ji J, Shu D, Zheng M, Wang J, Luo C, Wang Y, Guo F, Zou X, Lv X, Li Y, Liu T, Qu H - Sci Rep (2016)

Bottom Line: Metabolites from intestinal microbes modulate the mucosal immune system by regulating the polarization and expansion of T cells.Butyrate attenuated intestinal inflammation in mice with dextran sulfate sodium (DSS)-induced colitis, with a significant increase in colonic expression of the M2 macrophage-associated protein, Arg1.Collectively, our study indicated that commensal microbe-derived butyrate is a novel activator of STAT6-mediated transcription through H3K9 acetylation driving M2 macrophage polarization, and delineated new insights into the immune interplay underlying inflammatory bowel disease.

View Article: PubMed Central - PubMed

Affiliation: Institute of Animal Science, Guangdong Academy of Agricultural Sciences, 1 Dafeng 1st Street, Wushan, Tianhe District, Guangzhou 510640, China.

ABSTRACT
Metabolites from intestinal microbes modulate the mucosal immune system by regulating the polarization and expansion of T cells. Whether the microbial metabolites influence macrophage polarization, however, is poorly understood. Here, we show that the large bowel microbial fermentation product, butyrate, facilitates M2 macrophage polarization, in vitro and in vivo. The supernatant from butyrate-treated M2 macrophage increased the migration and enhanced the wound closure rate of MLE-12 cells. Butyrate attenuated intestinal inflammation in mice with dextran sulfate sodium (DSS)-induced colitis, with a significant increase in colonic expression of the M2 macrophage-associated protein, Arg1. M2 macrophage treated with butyrate, had increased activation of the H3K9/STAT6 signaling pathway, suggesting a mechanism for butyrate facilitated M2 macrophage polarization. Collectively, our study indicated that commensal microbe-derived butyrate is a novel activator of STAT6-mediated transcription through H3K9 acetylation driving M2 macrophage polarization, and delineated new insights into the immune interplay underlying inflammatory bowel disease.

No MeSH data available.


Related in: MedlinePlus

Effect of butyrate on dextran sulfate sodium (DSS)-induced colitis.(a) Relative body weight change, (b) disease activity index, (c) and colon length of mice with colitis treated with butyrate (+But) or left untreated (DSS), and healthy control mice (control). (d) Histological appearance and histological scores of colons from control mice, and mice with colitis, either treated with butyrate or untreated. (e) IL-1β, IL-6, and TNF-α in the serum of mice with colitis, treated with butyrate or untreated, and control mice. (f) Quantitation of the colonic Arg1 protein expression in serial sections by immunohistochemistry. The mean integrated optical density (IOD) (IOD/total area) represents the Arg1 expression level. Data are representative of 6 mice/group, with similar staining. Data are shown as mean ± SD for three independent experiments, Comparisons between means used t tests (*P < 0.05, **P < 0.01, ***P < 0.001).
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f3: Effect of butyrate on dextran sulfate sodium (DSS)-induced colitis.(a) Relative body weight change, (b) disease activity index, (c) and colon length of mice with colitis treated with butyrate (+But) or left untreated (DSS), and healthy control mice (control). (d) Histological appearance and histological scores of colons from control mice, and mice with colitis, either treated with butyrate or untreated. (e) IL-1β, IL-6, and TNF-α in the serum of mice with colitis, treated with butyrate or untreated, and control mice. (f) Quantitation of the colonic Arg1 protein expression in serial sections by immunohistochemistry. The mean integrated optical density (IOD) (IOD/total area) represents the Arg1 expression level. Data are representative of 6 mice/group, with similar staining. Data are shown as mean ± SD for three independent experiments, Comparisons between means used t tests (*P < 0.05, **P < 0.01, ***P < 0.001).

Mentions: M2 macrophage plays an important role in colonic infection with parasitic nematodes16. Furthermore, an increase in intestinal M2 macrophage has been associated with reducing the severity of colitis in mice17. We first evaluated the therapeutic effect of butyrate on DSS-induced colitis as a model of inflammatory bowel disease (IBD). Butyrate-treated mice showed much milder symptoms than the untreated colitis control mice, as evidenced by a slower rate of weight loss (Fig. 3a) and a lower disease activity index (DAI; Fig. 3b). Meanwhile, butyrate could promote the growth in mice and the results are consistent with the butyrate can improve the growth performance of animals181920. Histological examination of the colons showed less mucosal damage, demonstrating the protective effect of butyrate against colitis in the DSS-induced colitis model (Fig. 3c,d). Following butyrate treatment, reduced levels of proinflammatory cytokines, namely IL-6, TNF-α, and IL-1β, were detected in the serum compared with control mice (Fig. 3e). Moreover, we found that butyrate-treated mice had more Arg1 protein expression in colonic tissues (Fig. 3f). Taken together, these data showed that butyrate-treated mice have reduced clinical disease and histological damage compared with control mice, and this protection during DSS-induced colitis may correlate with increased in Arg1 protein expression in the colon during inflammation.


Microbial metabolite butyrate facilitates M2 macrophage polarization and function.

Ji J, Shu D, Zheng M, Wang J, Luo C, Wang Y, Guo F, Zou X, Lv X, Li Y, Liu T, Qu H - Sci Rep (2016)

Effect of butyrate on dextran sulfate sodium (DSS)-induced colitis.(a) Relative body weight change, (b) disease activity index, (c) and colon length of mice with colitis treated with butyrate (+But) or left untreated (DSS), and healthy control mice (control). (d) Histological appearance and histological scores of colons from control mice, and mice with colitis, either treated with butyrate or untreated. (e) IL-1β, IL-6, and TNF-α in the serum of mice with colitis, treated with butyrate or untreated, and control mice. (f) Quantitation of the colonic Arg1 protein expression in serial sections by immunohistochemistry. The mean integrated optical density (IOD) (IOD/total area) represents the Arg1 expression level. Data are representative of 6 mice/group, with similar staining. Data are shown as mean ± SD for three independent experiments, Comparisons between means used t tests (*P < 0.05, **P < 0.01, ***P < 0.001).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4837405&req=5

f3: Effect of butyrate on dextran sulfate sodium (DSS)-induced colitis.(a) Relative body weight change, (b) disease activity index, (c) and colon length of mice with colitis treated with butyrate (+But) or left untreated (DSS), and healthy control mice (control). (d) Histological appearance and histological scores of colons from control mice, and mice with colitis, either treated with butyrate or untreated. (e) IL-1β, IL-6, and TNF-α in the serum of mice with colitis, treated with butyrate or untreated, and control mice. (f) Quantitation of the colonic Arg1 protein expression in serial sections by immunohistochemistry. The mean integrated optical density (IOD) (IOD/total area) represents the Arg1 expression level. Data are representative of 6 mice/group, with similar staining. Data are shown as mean ± SD for three independent experiments, Comparisons between means used t tests (*P < 0.05, **P < 0.01, ***P < 0.001).
Mentions: M2 macrophage plays an important role in colonic infection with parasitic nematodes16. Furthermore, an increase in intestinal M2 macrophage has been associated with reducing the severity of colitis in mice17. We first evaluated the therapeutic effect of butyrate on DSS-induced colitis as a model of inflammatory bowel disease (IBD). Butyrate-treated mice showed much milder symptoms than the untreated colitis control mice, as evidenced by a slower rate of weight loss (Fig. 3a) and a lower disease activity index (DAI; Fig. 3b). Meanwhile, butyrate could promote the growth in mice and the results are consistent with the butyrate can improve the growth performance of animals181920. Histological examination of the colons showed less mucosal damage, demonstrating the protective effect of butyrate against colitis in the DSS-induced colitis model (Fig. 3c,d). Following butyrate treatment, reduced levels of proinflammatory cytokines, namely IL-6, TNF-α, and IL-1β, were detected in the serum compared with control mice (Fig. 3e). Moreover, we found that butyrate-treated mice had more Arg1 protein expression in colonic tissues (Fig. 3f). Taken together, these data showed that butyrate-treated mice have reduced clinical disease and histological damage compared with control mice, and this protection during DSS-induced colitis may correlate with increased in Arg1 protein expression in the colon during inflammation.

Bottom Line: Metabolites from intestinal microbes modulate the mucosal immune system by regulating the polarization and expansion of T cells.Butyrate attenuated intestinal inflammation in mice with dextran sulfate sodium (DSS)-induced colitis, with a significant increase in colonic expression of the M2 macrophage-associated protein, Arg1.Collectively, our study indicated that commensal microbe-derived butyrate is a novel activator of STAT6-mediated transcription through H3K9 acetylation driving M2 macrophage polarization, and delineated new insights into the immune interplay underlying inflammatory bowel disease.

View Article: PubMed Central - PubMed

Affiliation: Institute of Animal Science, Guangdong Academy of Agricultural Sciences, 1 Dafeng 1st Street, Wushan, Tianhe District, Guangzhou 510640, China.

ABSTRACT
Metabolites from intestinal microbes modulate the mucosal immune system by regulating the polarization and expansion of T cells. Whether the microbial metabolites influence macrophage polarization, however, is poorly understood. Here, we show that the large bowel microbial fermentation product, butyrate, facilitates M2 macrophage polarization, in vitro and in vivo. The supernatant from butyrate-treated M2 macrophage increased the migration and enhanced the wound closure rate of MLE-12 cells. Butyrate attenuated intestinal inflammation in mice with dextran sulfate sodium (DSS)-induced colitis, with a significant increase in colonic expression of the M2 macrophage-associated protein, Arg1. M2 macrophage treated with butyrate, had increased activation of the H3K9/STAT6 signaling pathway, suggesting a mechanism for butyrate facilitated M2 macrophage polarization. Collectively, our study indicated that commensal microbe-derived butyrate is a novel activator of STAT6-mediated transcription through H3K9 acetylation driving M2 macrophage polarization, and delineated new insights into the immune interplay underlying inflammatory bowel disease.

No MeSH data available.


Related in: MedlinePlus