Resistant starch intake alleviates collagen-induced arthritis in mice by modulating gut microbiota and promoting concomitant propionate production
Resistant starch intake alleviates collagen-induced arthritis in mice by modulating gut microbiota and promoting concomitant propionate production
复制标题
抗性淀粉摄入可通过调节肠道微生物群和促进丙酸产生来缓解小鼠胶原诱导的关节炎
DOI：
10.1016/j.jaut.2020.102564
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发表时间：
2021-01-01
影响因子：
12.8
通讯作者：
Luo, Yubin
中科院分区：
文献类型：
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作者：
Bai, Yunqiang;Li, Yanhong;Luo, Yubin
肠道菌群失调先于类风湿关节炎（RA）的临床症状出现，并与RA的发病和持续存在有关。RA的早期治疗对取得更好的临床结果至关重要，尤其是在关节破坏方面。尽管据报道饮食干预对RA患者有益，但饮食诱导的肠道微生物组变化是否可作为预防RA发展的策略尚不清楚。在此，我们研究了富含抗性淀粉（RS）的高纤维饮食（HFD）对小鼠胶原诱导性关节炎（CIA）和肠道微生物组成的影响。RS - HFD显著降低了CIA小鼠的关节炎严重程度和骨侵蚀。RS - HFD的治疗效果与脾脏调节性T细胞（Treg）扩增以及血清白细胞介素 - 10（IL - 10）增加相关。在喂食RS - HFD饮食的CIA小鼠中，伴随CIA出现的乳酸杆菌属和毛螺菌属丰度增加的情况消失了。值得注意的是，RS - HFD还导致拟杆菌门占优势，并使CIA小鼠中毛螺菌科_NK4A136_group和拟杆菌目_S24 - 7_group属的丰度增加。随着肠道微生物组的变化，通过气相色谱 - 飞行时间质谱（GC - TOFMS）检测到的CIA小鼠喂食RS - HFD后血清短链脂肪酸（SCFA）乙酸盐、丙酸盐和异丁酸盐水平也有所增加。然而，在喂食RS - HFD的小鼠饮用水中添加啤酒花提取物中的β - 酸，显著降低了血清丙酸盐，并完全消除了RS - HFD诱导的CIA小鼠疾病改善、Treg细胞增加和IL - 10产生。此外，在饮用水中添加外源性丙酸盐复制了RS - HFD在CIA中的保护作用，包括减少骨损伤。进一步探索了丙酸盐在体外对T细胞的直接作用，作为微生物代谢产物在实验性RA中对免疫调节的饮食效应的至少一种机制解释。总之，RS - HFD显著减轻了CIA和骨损伤，改变了肠道微生物组成，同时循环丙酸盐增加，这表明富含RS的饮食可能是一种有前景的治疗方法，尤其是在RA的早期阶段。
Gut dysbiosis precedes clinic symptoms in rheumatoid arthritis (RA) and has been implicated in the initiation and persistence of RA. The early treatment of RA is critical to better clinical outcome especially for joint destruction. Although dietary interventions have been reported to be beneficial for RA patients, it is unclear to whether diet-induced gut microbiome changes can be a preventive strategy to RA development. Here, we investigated the effect of a high fiber diet (HFD) rich with resistant starch (RS) on collagen-induced arthritis (CIA) and gut microbial composition in mice. RS-HFD significantly reduced arthritis severity and bone erosion in CIA mice. The therapeutic effects of RS-HFD were correlated with splenic regulatory T cell (Treg) expansion and serum interleukin-10 (IL-10) increase. The increased abundance of Lactobacillus and Lachnoclostridium genera concomitant with CIA were eliminated in CIA mice fed the RS-HFD diet. Notably, RS-HFD also led to a predominance of Bacteroidetes, and increased abundances of Lachnospiraceae_NK4A136_group and Bacteroidales_S24-7_group genera in CIA mice. Accompanied with the gut microbiome changes, serum levels of the short-chain fatty acid (SCFA) acetate, propionate and isobutyrate detected by GC-TOFMS were also increased in CIA mice fed RSHFD. While, addition of beta-acids from hops extract to the drinking water of mice fed RS-HFD significantly decreased serum propionate and completely eliminated RS-HFD-induced disease improvement, Treg cell increase and IL-10 production in CIA mice. Moreover, exogenous propionate added to drinking water replicated the protective role of RS-HFD in CIA including reduced bone damage. The direct effect of propionate on T cells in vitro was further explored as at least one mechanistic explanation for the dietary effects of microbial metabolites on immune regulation in experimental RA.Taken together, RS-HFD significantly reduced CIA and bone damage and altered gut microbial composition with concomitant increase in circulating propionate, indicating that RS-rich diet might be a promising therapy especially in the early stage of RA.