An analysis of the role of the indigenous microbiota in cholesterol gallstone pathogenesis.

An analysis of the role of the indigenous microbiota in cholesterol gallstone pathogenesis.
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DOI:
10.1371/journal.pone.0070657
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Maurer KJ
Maurer KJ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Fremont-Rahl JJ;Ge Z;Umana C;Whary MT;Taylor NS;Muthupalani S;Carey MC;Fox JG;Maurer KJ

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胆固醇结石病是一个涉及遗传和环境变量的复杂过程。没有关于本土胃肠道微生物群在胆固醇结石发病机制中可能发挥的作用以及微生物群的变化是否可以改变胆固醇结石患病率的信息。在喂食致石性饮食8周后,比较从不同供应商获得的小鼠的遗传相关亚系(BALB/cJ和BALB/cJBomTac)和(BALB/AnNTac和BALB/cByJ)的胆固醇结石患病率。在这些亚株中,通过经口灌胃粪便浆(作为成年动物)、通过交叉培养具有不同植物群(<1日龄)的小鼠或通过重新衍生为无菌状态,改变了固有微生物组。在传统饲养的SPF小鼠中,本土微生物组的改变显著改变了粘蛋白凝胶的积累和正常化的胆囊重量,但没有改变胆固醇结石的易感性。无菌再衍生使小鼠更容易形成胆固醇结石。这种易感性似乎主要是由于胆囊大小和胆囊壁炎症的改变。用改变的Schaedler植物群的成员定殖无菌小鼠使胆结石表型正常化至与常规饲养的小鼠相似的水平。这些数据表明,胃肠道微生物组的改变可能会改变胆固醇结石发病机制的各个方面,在适当的情况下,这些变化可能会影响胆固醇结石的发生。
Cholesterol gallstone disease is a complex process involving both genetic and environmental variables. No information exists regarding what role if any the indigenous gastrointestinal microbiota may play in cholesterol gallstone pathogenesis and whether variations in the microbiota can alter cholesterol gallstone prevalence rates. Genetically related substrains (BALB/cJ and BALB/cJBomTac) and (BALB/AnNTac and BALB/cByJ) of mice obtained from different vendors were compared for cholesterol gallstone prevalence after being fed a lithogenic diet for 8 weeks. The indigenous microbiome was altered in these substrains by oral gavage of fecal slurries as adults, by cross-fostering to mice with divergent flora at <1day of age or by rederiving into a germ-free state. Alterations in the indigenous microbiome altered significantly the accumulation of mucin gel and normalized gallbladder weight but did not alter cholesterol gallstone susceptibility in conventionally housed SPF mice. Germ-free rederivation rendered mice more susceptible to cholesterol gallstone formation. This susceptibility appeared to be largely due to alterations in gallbladder size and gallbladder wall inflammation. Colonization of germ-free mice with members of altered Schaedler flora normalized the gallstone phenotype to a level similar to conventionally housed mice. These data demonstrate that alterations in the gastrointestinal microbiome may alter aspects of cholesterol gallstone pathogenesis and that in the appropriate circumstances these changes may impact cholesterol cholelithogenesis.
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