Bifidobacterium longum CECT 7894 Improves the Efficacy of Infliximab for DSS-Induced Colitis via Regulating the Gut Microbiota and Bile Acid Metabolism.
Bifidobacterium longum CECT 7894 Improves the Efficacy of Infliximab for DSS-Induced Colitis via Regulating the Gut Microbiota and Bile Acid Metabolism.
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长双歧杆菌 CECT 7894 通过调节肠道微生物群和胆汁酸代谢提高英夫利昔单抗治疗 DSS 诱导的结肠炎的疗效
DOI：
10.3389/fphar.2022.902337
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发表时间：
2022
影响因子：
5.6
通讯作者：
Zhang, Ting
中科院分区：
文献类型：
--
作者：
Xiao, Fangfei;Dong, Fang;Li, Xiaolu;Li, Youran;Yu, Guangjun;Liu, Zhanju;Wang, Yizhong;Zhang, Ting
背景：最近的证据表明，肠道微生物区系及其代谢产物的变化可以预测英夫利昔单抗(ifliximab，IFX)等抗肿瘤坏死因子药物的临床疗效。然而，操纵肠道微生物区系是否能增强抗肿瘤坏死因子药物的疗效仍不清楚。在此，我们旨在评价益生菌双歧杆菌长双歧杆菌CECT 7894对葡聚糖硫酸钠(DSS)诱导的小鼠结肠炎的IFX疗效的影响，并试图探讨其潜在的相关机制。方法：用磷酸盐缓冲液(PBS)或长链杆菌CECT7894(5×108CFU/d)灌胃给C57BL/6小鼠，每天1次，连续5d，然后用3%(w/v)DSS饮水诱导小鼠急性结肠炎。通过体重减轻、粪便浓度、结肠长度和组织病理学变化评估IFX与或不与长杆菌CECT7894联合使用的疗效。免疫组织化学方法检测结肠组织中紧密连接蛋白(TJPs)的表达。经16次S rRNA基因测序鉴定其微生物区系组成。用靶向代谢组学分析粪便胆汁酸(BAS)水平。结果：与单纯使用IFX的小鼠相比，B.long um CECT 7894提高了IFX对DSS诱导的结肠炎的疗效，表现为体重减轻、疾病活动指数(DAI)评分、结肠长度缩短、组织学损伤、ZO-1和occludin表达增加。B.long um CECT 7894改变了DSS诱导的结肠炎小鼠肠道微生物群落的组成和结构。长杆菌CECT 7894提高了双歧杆菌属、布鲁氏菌属、丁霉菌属、梭状芽孢杆菌属、嗜酸杆菌属、革兰氏杆菌属和副杆菌属的相对丰度，降低了肠球菌属和假单胞菌属的相对丰度。此外，B.long um CECT 7894还通过增加次生BAs的丰度来改变BAs的代谢，如a-MCA、ç-MCA、LCA、CDCA、UDCA、HCA、isLCA、isallLCA。协方差分析显示，次级BA的上调与含有胆盐水解酶和7个α-脱羟酶基因的细菌的丰度增加呈正相关。结论：长杆菌CECT 7894可通过调节肠道微生物区系组成和胆汁酸代谢，提高IFX治疗DSS所致结肠炎的疗效。益生菌的补充可能为改善抗肿瘤坏死因子制剂在IBD治疗中的临床疗效提供可能性。
Background: Recent evidence suggests that the changes in gut microbiota and its metabolites could predict the clinical response of anti-tumor necrosis factor (TNF) agents, such as infliximab (IFX). However, whether manipulation of the gut microbiota can enhance the efficacy of anti-TNF agents remains unclear. Here, we aim to evaluate the effect of a probiotic strain, Bifidobacterium longum (B. longum) CECT 7894, on IFX efficacy for dextran sulfate sodium (DSS)-induced colitis in mice and attempt to explore the potential involved mechanisms. Methods: C57BL/6 mice were treated with phosphate-buffered saline (PBS) or B. longum CECT 7894 (5 × 108 CFU/day) once daily by gavage for 5 days and subsequently induced acute colitis by 3% (w/v) DSS in drinking water. The efficacies of IFX combined with or without B. longum CECT 7894 were assessed by weight loss, fecal consistency, colon length, and histopathological changes. Immunohistochemistry (IHC) was used to examine the expression of tight junction proteins (TJPs) in colonic tissues. The microbiota composition was characterized through 16 S rRNA gene sequencing. Fecal bile acids (BAs) levels were analyzed by targeted metabolomics. Results: B. longum CECT 7894 improved the efficacy of IFX for DSS-induced colitis as evidenced by decreased weight loss, disease activity index (DAI) scores, colon length shortening, histological damage, increased ZO-1, and Occludin expressions as compared with mice that received IFX only. B. longum CECT 7894 modified the composition and structure of the gut microbiota community in DSS-induced colitis mice. B. longum CECT 7894 increased the relative abundances of genera Bifidobacterium, Blautia, Butyricicoccus, Clostridium, Coprococcus, Gemmiger, and Parabacterioides, and reduced the relative abundances of bacteria genera Enterococcus and Pseudomonas. Furthermore, B. longum CECT 7894 changed the BAs metabolism by increasing the abundance of secondary BAs, such as a-MCA, ß-MCA, LCA, CDCA, UDCA, HCA, isoLCA, isoalloLCA. The covariance analysis revealed the upregulated secondary BAs were positively associated with the increased abundance of bacteria that contained bile salt hydrolases (BSH) and 7α-dehydroxylases genes. Conclusion: B. longum CECT 7894 improved the efficacy of IFX for DSS-induced colitis via regulating the gut microbiota composition and bile acid metabolism. Probiotics supplementation may provide a possibility to improve the clinical response of anti-TNF agents in IBD management.
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影响因子：
32.4
作者：
Dorrestein PC;Mazmanian SK;Knight R
通讯作者：
Knight R
影响因子：
48
作者：
Callahan BJ;McMurdie PJ;Rosen MJ;Han AW;Johnson AJ;Holmes SP
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Kruis, W;Fric, P;Schulze, J
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Schulze, J
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29.4
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通讯作者：
Neurath, Markus F.
影响因子：
64.8
作者：
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通讯作者：
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