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A key genetic factor governing arabinan utilization in the gut microbiome alleviates constipation
Cell Host & Microbe ( IF 30.3 ) Pub Date : 2023-11-21 , DOI: 10.1016/j.chom.2023.10.011
Chengcheng Zhang 1 , Leilei Yu 1 , Chenchen Ma 2 , Shuaiming Jiang 2 , Yufeng Zhang 3 , Shunhe Wang 1 , Fengwei Tian 1 , Yuzheng Xue 4 , Jianxin Zhao 1 , Hao Zhang 1 , Liming Liu 5 , Wei Chen 1 , Shi Huang 3 , Jiachao Zhang 2 , Qixiao Zhai 1
Affiliation  

Impaired gastrointestinal motility is associated with gut dysbiosis. Probiotics, such as Bifidobacteria, can improve this bowel disorder; however, efficacy is strain-dependent. We determine that a genetic factor, the abfA cluster governing arabinan utilization, in Bifidobacterium longum impacts treatment efficacy against functional constipation (FC). In mice with FC, B. longum, but not an abfA mutant, improved gastrointestinal transit time, an affect that was dependent upon dietary arabinan. abfA genes were identified in other commensal bacteria, whose effects in ameliorating murine FC were similarly abfA-dependent. In a double-blind, randomized, placebo-controlled clinical trial, supplementation with abfA-cluster-carrying B. longum, but not an abfA-deficient strain, enriched arabinan-utilization residents, increased beneficial metabolites, and improved FC symptoms. Across human cohorts, abfA-cluster abundance can predict FC, and transplantation of abfA cluster-enriched human microbiota to FC-induced germ-free mice improved gut motility. Collectively, these findings demonstrate a role for microbial abfA cluster in ameliorating FC, establishing principles for genomics-directed probiotic therapies.



中文翻译:


控制肠道微生物组中阿拉伯聚糖利用的关键遗传因素可缓解便秘



胃肠道运动受损与肠道菌群失调有关。益生菌,例如双歧杆菌,可以改善这种肠道疾病;然而,功效取决于菌株。我们确定长双歧杆菌中控制阿拉伯聚糖利用的遗传因素 abfA 簇会影响功能性便秘 (FC) 的治疗效果。在患有 FC 的小鼠中,长双歧杆菌(而非 abfA 突变体)改善了胃肠道传输时间,这种影响取决于饮食中的阿拉伯聚糖。在其他共生细菌中也发现了 abfA 基因,其改善小鼠 FC 的作用同样依赖于 abfA。在一项双盲、随机、安慰剂对照临床试验中,补充携带 abfA 簇的长双歧杆菌(而非 abfA 缺陷菌株)可丰富阿拉伯聚糖利用居民,增加有益代谢物,并改善 FC 症状。在人类队列中,abfA 簇丰度可以预测 FC,将富含 abfA 簇的人类微生物群移植到 FC 诱导的无菌小鼠中可以改善肠道蠕动。总的来说,这些发现证明了微生物 abfA 簇在改善 FC 中的作用,为基因组学导向的益生菌疗法确立了原则。

更新日期:2023-11-21
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