Colonic Microbiota Encroachment Correlates With Dysglycemia in Humans.

Colonic Microbiota Encroachment Correlates With Dysglycemia in Humans.
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DOI:
10.1016/j.jcmgh.2017.04.001
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发表时间:
2017-09
影响因子:
7.2
通讯作者:
Gewirtz AT
Gewirtz AT
中科院分区:
医学1区
文献类型:
--
作者:
Chassaing B;Raja SM;Lewis JD;Srinivasan S;Gewirtz AT

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包裹上皮的粘液状结构在保持肠道微生物区系与宿主细胞之间的安全距离方面起着至关重要的作用。在炎症性肠病和小鼠结肠炎模型中,已经观察到细菌侵入正常情况下几乎无菌的内粘液层。此外,在代谢综合征的小鼠模型中也观察到了这种微生物群的侵蚀,代谢综合征与低度肠道炎症有关。因此,我们调查了微生物区系侵占是否可能与人类代谢综合征的指标相关。共聚焦显微镜被用来测量所有接受癌症筛查结肠镜检查的自愿参与者的结肠活检组织中每高倍视野中最接近的细菌-上皮距离。我们观察到,在所有受试者中,细菌-上皮距离与体重指数、空腹血糖水平和血红蛋白A1C呈负相关。然而,这种相关性是由血糖异常受试者驱动的,与体重指数无关,而肥胖和非肥胖者之间细菌-上皮距离的差异通过去除血糖紊乱受试者而消除。我们得出结论,微生物区系侵占是人类胰岛素抵抗相关性血糖紊乱的一个特征。
Mucoid structures that coat the epithelium play an essential role in keeping the intestinal microbiota at a safe distance from host cells. Encroachment of bacteria into the normally almost-sterile inner mucus layer has been observed in inflammatory bowel disease and in mouse models of colitis. Moreover, such microbiota encroachment has also been observed in mouse models of metabolic syndrome, which are associated low-grade intestinal inflammation. Hence, we investigated if microbiota encroachment might correlate with indices of metabolic syndrome in humans. Confocal microscopy was used to measure bacterial-epithelial distance of the closest bacteria per high-powered field in colonic biopsies of all willing participants undergoing cancer screening colonoscopies. We observed that, among all subjects, bacterial-epithelial distance was inversely correlated with body mass index, fasting glucose levels, and hemoglobin A1C. However, this correlation was driven by dysglycemic subjects, irrespective of body mass index, whereas the difference in bacterial-epithelial distance between obese and nonobese subjects was eliminated by removal of dysglycemic subjects. We conclude that microbiota encroachment is a feature of insulin resistance–associated dysglycemia in humans.