Synbiotics Bifidobacterium infantis and milk oligosaccharides are effective in reversing cancer-prone nonalcoholic steatohepatitis using western diet-fed FXR knockout mouse models.
Synbiotics Bifidobacterium infantis and milk oligosaccharides are effective in reversing cancer-prone nonalcoholic steatohepatitis using western diet-fed FXR knockout mouse models.
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合成生生物杆菌和牛奶的寡糖可有效使用西部饮食喂养的FXR敲除小鼠模型逆转易癌症的非酒精性脂肪性肝炎。
DOI：
10.1016/j.jnutbio.2018.04.007
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发表时间：
2018-07
期刊：
影响因子：
--
通讯作者：
Wan YY
中科院分区：
文献类型：
--
作者：
Jena PK;Sheng L;Nagar N;Wu C;Barile D;Mills DA;Wan YY
益生元乳寡糖 (MO) 是一种复合糖，可选择性促进婴儿双歧杆菌 (B.infantis) 的生长。目前的研究探讨了牛 MO 和婴儿双歧杆菌在西方饮食 (WD) 喂养的胆汁酸 (BA) 受体 FXR（法尼醇 × 受体）敲除 (KO) 小鼠中预防非酒精性脂肪性肝炎 (NASH) 的作用。 WD 喂养的 FXR KO 小鼠具有易患癌症的 NASH 且婴儿双歧杆菌减少，并补充了婴儿双歧杆菌、MO 以及两者的组合。婴儿双歧杆菌和/或 MO 的两个月干预改善了胰岛素敏感性。此外，所有 3 种治疗方法均减少了肝脏和回肠中促炎基因的表达。一致地，7 个月的治疗减少了 WD 喂养的 FXR KO 小鼠的肝淋巴细胞浸润。此外，婴儿双歧杆菌（而非 MO）可以降低肝脏甘油三酯和胆固醇。两者结合可进一步降低肝胆固醇（BA 的前体），但不会降低肝甘油三酯。所有三种治疗均通过降低脱氧胆酸、猪去氧胆酸和增加鹅去氧胆酸以及熊去氧胆酸水平来调节肝脏和血清BA谱。此外，婴儿双歧杆菌和 MO 降低肝脏 CYP7A1 并增加 Sult2a1、Sult2a2 和 Sult2a3 的表达，表明 BA 合成减少和解毒增加。此外，婴儿双歧杆菌和 MO 增加了回肠 BA 膜受体 TGR5 以及 Glp1r、PC1/3 和 Nos3，表明 TGR5 调节的信号传导增加。此外，单独的 MO（而不是婴儿双歧杆菌）可以增加产生丁酸的细菌的丰度，这对 NASH 治疗具有有益的作用。婴儿双歧杆菌和 MO 在逆转 WD 喂养的 FXR KO 小鼠 NASH 方面具有独特的综合作用。
Prebiotic milk oligosaccharides (MO) are complex sugars that selectively enhance the growth of Bifidobacterium infantis (B. infantis). The current study examines the effects of bovine MO and B. infantis in preventing non-alcoholic steatohepatitis (NASH) in Western diet (WD)-fed bile acid (BA) receptor FXR (farnesoid × receptor) knockout (KO) mice. WD-fed FXR KO mice, which have cancer-prone NASH and reduced B. infantis, were supplemented with B. infantis, MO, and combination of both. Two months intervention by B. infantis and/or MO improved insulin sensitivity. In addition, all 3 treatments reduced expression of pro-inflammatory genes in the liver and ileum. Consistently, 7 months treatment reduced hepatic lymphocyte infiltration in WD-fed FXR KO mice. In addition, B. infantis, but not MO, decreased hepatic triglyceride and cholesterol. A combination of both further reduced hepatic cholesterol, the precursor of BAs, but not hepatic triglyceride. All three treatments modulated hepatic and serum BA profile by reducing deoxycholic acid, hyodeoxycholic acid and increasing chenodeoxycholic acid as well as ursodeoxycholic acid level. In addition, B. infantis and MO decreased hepatic CYP7A1 and increased the expression of Sult2a1, Sult2a2, and Sult2a3 suggesting decreased BA synthesis and increased detoxification. Furthermore, B. infantis and MO increased ileal BA membrane receptor TGR5 as well as Glp1r, PC1/3, and Nos3 suggesting increased TGR5-regulated signaling. Moreover, MO alone, but not B. infantis, could increase the abundance of butyrate-generating bacterium that has beneficial effect in NASH treatment. Together, B. infantis and MO have their unique and combined effects in reversing NASH in WD-fed FXR KO mice.
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影响因子：
3
作者：
Huang F;Wang T;Lan Y;Yang L;Pan W;Zhu Y;Lv B;Wei Y;Shi H;Wu H;Zhang B;Wang J;Duan X;Hu Z;Wu X
通讯作者：
Wu X
影响因子：
6.5
作者：
Jung, Diana;Inagaki, Takeshi;Moschetta, Antonio
通讯作者：
Moschetta, Antonio
影响因子：
2.3
作者：
Akay, Hatice Kubra;Tokman, Hrisi Bahar;Kocazeybek, Bekir S.
通讯作者：
Kocazeybek, Bekir S.
影响因子：
4.3
作者：
Aldredge, Danielle L.;Geronimo, Maria R.;Barile, Daniela
通讯作者：
Barile, Daniela
影响因子：
7.1
作者：
Bezkorovainy, A
通讯作者：
Bezkorovainy, A