Dietary emulsifiers directly alter human microbiota composition and gene expression ex vivo potentiating intestinal inflammation.
Dietary emulsifiers directly alter human microbiota composition and gene expression ex vivo potentiating intestinal inflammation.
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DOI：
10.1136/gutjnl-2016-313099
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发表时间：
2017-08
期刊：
影响因子：
24.5
通讯作者：
Gewirtz AT
中科院分区：
文献类型：
--
作者：
Chassaing B;Van de Wiele T;De Bodt J;Marzorati M;Gewirtz AT
肠道微生物群在包括炎症性肠病和代谢综合征在内的许多慢性炎症性疾病的发展中起着核心作用。使用改变微生物群组成的物质，包括合成的膳食乳化剂聚山梨酸酯80 （P80）和羧甲基纤维素（CMC），可以促进这种炎症性疾病。然而，炎症本身对微生物群组成的影响使这些化合物或其他物质直接作用于微生物群的程度与作用于促进炎症的宿主参数的程度变得模糊，后者随后重塑了微生物群。我们使用人类肠道微生物生态系统（M-SHIME）模型的粘膜模拟器检测了CMC和P80对微生物群的直接影响，该模型在没有活宿主的情况下维持复杂稳定的人类微生物群。该方法表明，P80和CMC都直接作用于人类微生物群，增加其促炎潜能，正如生物活性鞭毛蛋白水平增加所揭示的那样。cmc诱导的鞭毛蛋白的增加是快速的（1天），由微生物群基因表达的改变驱动。相比之下，p80诱导的鞭毛蛋白增加发生得更慢，并且与物种组成的改变密切相关。将两种乳化剂处理过的M-SHIME微生物转移到无菌受体小鼠中，再现了在直接用乳化剂处理的小鼠中观察到的许多宿主和微生物变化。这些结果展示了一种解构宿主-微生物群相互作用的新范式，并表明微生物群可以直接受到这些常用食品添加剂的影响，从而导致肠道炎症。
The intestinal microbiota plays a central role in the development of many chronic inflammatory diseases including inflammatory bowel disease and metabolic syndrome. Administration of substances that alter microbiota composition, including the synthetic dietary emulsifiers polysorbate 80 (P80) and carboxymethylcellulose (CMC), can promote such inflammatory disorders. However, that inflammation itself impacts microbiota composition has obfuscated defining the extent to which these compounds or other substances act directly upon the microbiota versus acting on host parameters that promote inflammation, which subsequently reshapes the microbiota. We examined the direct impact of CMC and P80 on the microbiota using the mucosal simulator of the human intestinal microbial ecosystem (M-SHIME) model that maintains a complex stable human microbiota in the absence of a live host. This approach revealed that both P80 and CMC acted directly upon human microbiota to increase its pro-inflammatory potential, as revealed by increased levels of bioactive flagellin. The CMC-induced increase in flagellin was rapid (1 day) and driven by altered microbiota gene expression. In contrast, the P80-induced flagellin increase occurred more slowly and was closely associated with altered species composition. Transfer of both emulsifier-treated M-SHIME microbiotas to germ-free recipient mice recapitulated many of the host and microbial alterations observed in mice directly treated with emulsifiers. These results demonstrate a novel paradigm of deconstructing host-microbiota interactions and indicate that the microbiota can be directly impacted by these commonly used food additives, in a manner that subsequently drives intestinal inflammation.
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影响因子：
64.8
作者：
Chassaing B;Koren O;Goodrich JK;Poole AC;Srinivasan S;Ley RE;Gewirtz AT
通讯作者：
Gewirtz AT
影响因子：
12.3
作者：
Lloyd-Price J;Abu-Ali G;Huttenhower C
通讯作者：
Huttenhower C
影响因子：
64.8
作者：
Devkota, Suzanne;Wang, Yunwei;Musch, Mark W.;Leone, Vanessa;Fehlner-Peach, Hannah;Nadimpalli, Anuradha;Antonopoulos, Dionysios A.;Jabri, Bana;Chang, Eugene B.
通讯作者：
Chang, Eugene B.
影响因子：
8
作者：
Roberts, Carol L.;Rushworth, Sarah L.;Rhodes, Jonathan M.
通讯作者：
Rhodes, Jonathan M.
影响因子：
29.4
作者：
Metcalf, Amanda M.;Phillips, Sidney F.;Wolff, Bruce G.
通讯作者：
Wolff, Bruce G.