Gut Microbiota Dysbiosis Is Associated with Altered Bile Acid Metabolism in Infantile Cholestasis
Gut Microbiota Dysbiosis Is Associated with Altered Bile Acid Metabolism in Infantile Cholestasis
复制标题
肠道微生物群失调与婴儿胆汁淤积的胆汁酸代谢改变有关
DOI：
10.1128/msystems.00463-19
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发表时间：
2019-11-01
期刊：
影响因子：
6.4
通讯作者：
Zhang, Ting
中科院分区：
文献类型：
--
作者：
Wang, Yizhong;Gao, Xuefeng;Zhang, Ting
肝脏健康，粪便胆汁酸（BA）浓度和肠道微生物群组成密切相关。BA和微生物组在肠道中相互影响，其中细菌改变BA特征，而肠道BA调节肠道细菌的生长，维持屏障完整性，并调节免疫系统。以往的研究发现，肠道微生物群失调和BA代谢改变共同发生在许多人类肝脏疾病中。我们的研究是第一个评估婴儿胆汁淤积性黄疸（CJ）的肠道菌群组成，并阐明肠道细菌变化和BA代谢改变之间的联系。我们观察到CJ婴儿的原发性BA和大多数继发性BA水平降低。婴儿CJ中粪便BA浓度的降低与具有致病潜力的肠道细菌的过度生长和具有潜在益处的肠道细菌的耗尽有关。CJ婴儿肠道菌群的改变可能会上调从原发性BA到继发性BA的转化。我们的研究为针对婴儿CJ管理的肠道微生物群干预的潜在目标提供了新的视角。摘要肠道菌群失调和胆汁酸（BA）代谢改变在几种人类肝脏疾病中同时发生。然而，婴儿胆汁淤积性黄疸（CJ）的肠道微生物群失调以及肠道细菌变化与BA代谢改变之间的联系尚未确定。为了解决这个问题，我们进行了16 S rRNA基因测序，以确定CJ婴儿肠道微生物群的改变，并评估了它们与原发性和继发性BA粪便水平的相关性。我们的数据显示，CJ婴儿显示显着下降，在粪便中的初级BA和大多数二级BA的水平。CJ婴儿的胆酸（CA）/鹅去氧胆酸（CDCA）比值降低，表明BA合成从主要途径转变为替代BA合成途径。CJ患儿肠道菌群主要为梭菌属、双生菌属、链球菌属、韦荣球菌属和肠杆菌科，与粪便BA水平和CDCA/CA比值呈负相关，与肝功能损害的血清学指标呈正相关。在CJ婴儿中观察到脱氧胆酸（DCA）/CA的比例增加。CJ患儿体内的双歧杆菌、普氏粪杆菌等细菌的消耗量分别与粪便中的BA水平和肝功能损害的血清学标志物呈正相关和负相关。总之，CJ婴儿肠道中BA浓度的降低与肠道微生物群失调相关。CJ婴儿肠道菌群的改变可能会上调从原发性BA到继发性BA的转化。肝脏健康，粪便胆汁酸（BA）浓度和肠道微生物群组成密切相关。BA和微生物组在肠道中相互影响，其中细菌改变BA特征，而肠道BA调节肠道细菌的生长，维持屏障完整性，并调节免疫系统。以往的研究发现，肠道微生物群失调和BA代谢改变共同发生在许多人类肝脏疾病中。我们的研究是第一个评估婴儿胆汁淤积性黄疸（CJ）的肠道菌群组成，并阐明肠道细菌变化和BA代谢改变之间的联系。我们观察到CJ婴儿的原发性BA和大多数继发性BA水平降低。婴儿CJ中粪便BA浓度的降低与具有致病潜力的肠道细菌的过度生长和具有潜在益处的肠道细菌的耗尽有关。CJ婴儿肠道菌群的改变可能会上调从原发性BA到继发性BA的转化。我们的研究为针对婴儿CJ管理的肠道微生物群干预的潜在目标提供了新的视角。
Liver health, fecal bile acid (BA) concentrations, and gut microbiota composition are closely connected. BAs and the microbiome influence each other in the gut, where bacteria modify the BA profile, while intestinal BAs regulate the growth of commensal bacteria, maintain the barrier integrity, and modulate the immune system. Previous studies have found that the co-occurrence of gut microbiota dysbiosis and BA metabolism alteration is present in many human liver diseases. Our study is the first to assess the gut microbiota composition in infantile cholestatic jaundice (CJ) and elucidate the linkage between gut bacterial changes and alterations of BA metabolism. We observed reduced levels of primary BAs and most secondary BAs in infants with CJ. The reduced concentration of fecal BAs in infantile CJ was associated with the overgrowth of gut bacteria with a pathogenic potential and the depletion of those with a potential benefit. The altered gut microbiota of infants with CJ likely upregulates the conversion from primary to secondary BAs. Our study provides a new perspective on potential targets for gut microbiota intervention directed at the management of infantile CJ. ABSTRACT The co-occurrence of gut microbiota dysbiosis and bile acid (BA) metabolism alteration has been reported in several human liver diseases. However, the gut microbiota dysbiosis in infantile cholestatic jaundice (CJ) and the linkage between gut bacterial changes and alterations of BA metabolism have not been determined. To address this question, we performed 16S rRNA gene sequencing to determine the alterations in the gut microbiota of infants with CJ, and assessed their association with the fecal levels of primary and secondary BAs. Our data reveal that CJ infants show marked declines in the fecal levels of primary BAs and most secondary BAs. A decreased ratio of cholic acid (CA)/chenodeoxycholic acid (CDCA) in infants with CJ indicated a shift in BA synthesis from the primary pathway to the alternative BA synthesis pathway. The bacterial taxa enriched in infants with CJ corresponded to the genera Clostridium, Gemella, Streptococcus, and Veillonella and the family Enterobacteriaceae and were negatively correlated with the fecal BA level and the CDCA/CA ratio but positively correlated with the serological indexes of impaired liver function. An increased ratio of deoxycholic acid (DCA)/CA was observed in a proportion of infants with CJ. The bacteria depleted in infants with CJ, including Bifidobacterium and Faecalibacterium prausnitzii, were positively and negatively correlated with the fecal levels of BAs and the serological markers of impaired liver function, respectively. In conclusion, the reduced concentration of BAs in the gut of infants with CJ is correlated with gut microbiota dysbiosis. The altered gut microbiota of infants with CJ likely upregulates the conversion from primary to secondary BAs. IMPORTANCE Liver health, fecal bile acid (BA) concentrations, and gut microbiota composition are closely connected. BAs and the microbiome influence each other in the gut, where bacteria modify the BA profile, while intestinal BAs regulate the growth of commensal bacteria, maintain the barrier integrity, and modulate the immune system. Previous studies have found that the co-occurrence of gut microbiota dysbiosis and BA metabolism alteration is present in many human liver diseases. Our study is the first to assess the gut microbiota composition in infantile cholestatic jaundice (CJ) and elucidate the linkage between gut bacterial changes and alterations of BA metabolism. We observed reduced levels of primary BAs and most secondary BAs in infants with CJ. The reduced concentration of fecal BAs in infantile CJ was associated with the overgrowth of gut bacteria with a pathogenic potential and the depletion of those with a potential benefit. The altered gut microbiota of infants with CJ likely upregulates the conversion from primary to secondary BAs. Our study provides a new perspective on potential targets for gut microbiota intervention directed at the management of infantile CJ.