健康的肠道菌群或可抑制个体代谢综合征的发生

  近日，来自乔治亚州立大学和康奈尔大学的研究人员发表在国际杂志Gastroenterology上的一篇研究论文指出，促进肠道细菌的健康或可以帮助治疗或者预防代谢综合征的发生，代谢综合征 （Metabolic syndrome）是一组与超重或肥胖相关的危险因素的总称，其会增加个体患心脏病、糖尿病及中风的风险。

  研究者Andrew Gewirtz表示，本文研究中我们开发了一种新方法来促进肠道微生物的健康从而有效抑制代谢性疾病的发生；而且我们也证实了，改变肠道菌群可以帮助促进低程度炎性及代谢征的发生，然而在改变肠道菌群的同时也会促进细菌对宿主的侵袭并且帮助细菌产生诸如鞭毛蛋白及脂多糖等物质，而这些物质会促进炎症的发生。

  据美国心脏协会数据显示，代谢综合征影响着34%的美国成年个体的健康，当个体出现如下症状时其就被诊断为代谢综合征，这些症状为：较宽的腰围、甘油三酯水平较高、高密度脂蛋白水平较低、高血压、空腹血糖水平较高。相比正常个体而言，代谢综合征个体患心脏疾病的可能性是前者的2倍，患糖尿病的可能性是前者的5倍。

  肠道微生物在个体机体健康中扮演着重要角色，当其失调后会促进慢性炎性疾病的发生，比如克罗恩病及溃疡性结肠炎；另外改变肠道微生物也会促进炎性发生，进而引发代谢综合征的发生。Gewirtz表示，我们通过研究揭示了改变肠道微生物引发代谢综合征的分子机理，文章中我们发现是肠道上皮细胞中的TLR5缺失了，上皮细胞可以对细菌快速产生反应，然而TLR5的缺失却会引发细菌的疯狂聚集进而产生一些诱发炎症的物质。

  研究者表示，改变肠道微生物可以促使其在上皮细胞中聚集进而产生鞭毛蛋白和脂多糖，从而加剧炎性的发生；而肠道上皮细胞中TLR5的缺失会改变肠道细菌，从而诱发炎症及代谢综合征的发生。本文研究为后期研究人员开发抑制代谢综合征发生的新型疗法提供了一定的思路和依据。（转化医学网360zhyx.com）

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Intestinal Epithelial Cell Toll-like Receptor 5 Regulates the Intestinal Microbiota to Prevent Low-Grade Inflammation and Metabolic Syndrome in Mice
Gastroenterology doi:10.1053/j.gastro.2014.08.033
Benoit Chassaing, Ruth E. Ley, Andrew T. Gewirtz
Background & Aims
Mice lacking the receptor Toll-like receptor 5 (TLR5-null mice), which recognizes flagellin, have an altered intestinal microbiota composition compared with wild-type mice; they develop low-grade inflammation and metabolic syndrome and are prone to colitis. The relative roles of intestinal epithelial cell (IEC) vs dendritic cell (DC) TLR5 in mediating these phenotypes are not clear; modification of intestinal microbiota composition has been reported to reflect animal husbandry practices rather than loss of TLR5. We generated mice with specific disruption of Tlr5 in IECs or DCs by using a breeding scheme that allows comparison with cohoused siblings as controls.
Methods
We generated C57BL/6 mice with LoxP sites flanking Tlr5. These mice were crossed with mice expressing Cre recombinase, regulated by the villin or CD11c promoters, to generate mice that lacked expression of TLR5 by IECs (TLR5ΔIEC) or DCs (TLR5ΔDC), respectively. Tlr5fl/fl siblings were used as controls. On weaning, mice were housed by sex and genotype or by sex only (genotypes cohoused). Mice were examined for basal phenotypes, including microbiota composition; we also analyzed responses to pathobiont challenge, administration of dextran sodium sulfate, and high-fat diets.
Results
Similar to previous findings from TLR5-null mice, TLR5ΔIEC mice had low-grade inflammation (mild splenomegaly, shortened colons, and increased fecal levels of lipocalin 2), metabolic syndrome, and an inability to clear pathobionts and were prone to developing colitis compared with their sibling controls under both housing conditions. Development of this inflammation in the TLR5ΔIEC mice was eliminated by administration of antibiotics and associated with alterations in localization of microbiota and levels of fecal lipopolysaccharide and flagellin. The composition of the microbiota clustered more closely according to genotype than housing. Loss of TLR5 from DCs did not associate with development of inflammation-associated phenotypes or alterations in the composition of the microbiota but resulted in complete loss of flagellin-induced production of interleukin-22.
Conclusions
In mice, flagellin activation of TLR5 on DCs leads to production of interleukin-22. Expression of TLR5 on IECs regulates the composition and localization of the intestinal microbiota, preventing diseases associated with intestinal inflammation.