长双歧杆菌CCFM1077通过调节肠道微生物组成和粪便代谢物来减轻高脂血症——一项随机、双盲、安慰剂对照的临床试验

储传奇, 姜金池, 于雷雷, 李易文, 张松礼, 周巍, 王群, 赵建新, 翟齐啸, 田丰伟, 陈卫

工程（英文） ›› 2023, Vol. 28 ›› Issue (9) : 193-205.

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工程（英文） ›› 2023, Vol. 28 ›› Issue (9) : 193-205. DOI: 10.1016/j.eng.2023.04.010
研究论文
Article

长双歧杆菌CCFM1077通过调节肠道微生物组成和粪便代谢物来减轻高脂血症——一项随机、双盲、安慰剂对照的临床试验

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Bifidobacterium longum CCFM1077 Attenuates Hyperlipidemia by Modulating the Gut Microbiota Composition and Fecal Metabolites: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

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摘要

越来越多的研究表明肠道菌群及其代谢物在高脂血症的发展中至关重要。长双歧杆菌（Bifidobacterium longum, B. longum）CCFM1077已在动物中显示出降脂作用。本研究旨在评估B. longum CCFM1077在降低高脂血症患者血脂水平方面的潜力，并调查该菌对患者的血清脂质异常、肠道菌群和粪便代谢物的影响。本研究是一个为期六周的随机、双盲、安慰剂对照的试验。高脂血症患者（N = 62）被随机分配接受安慰剂（N = 31）或B. longum CCFM1077 [每日1.0×1010个菌落形成单位（CFU）；N = 31]。在基线和干预终点检查了包括总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、总甘油三酯（TG）和高密度脂蛋白胆固醇（HDL-C）在内的血清脂质水平。肠道菌群组成和多样性的变化是基于16S核糖体RNA（rRNA）V3~V4区域的测序在干预期结束时进行。利用超高效液相色谱（UPLC）-Q-Exactive Orbitrap/质谱仪进行了粪便的非靶向代谢组学分析。口服B. longum CCFM1077六周显著降低了高脂血症患者的血清TC（p < 0.01）和LDL-C（p < 0.01）水平。B. longum CCFM1077的治疗显著增加了肠道菌群的多样性和抗肥胖相关属的相对丰度，包括Lactobacillus、Butyricicoccus、Bifidobacterium和Blautia，而减少了与肥胖相关属的相对丰度，包括Alistipes、Megamonas和Catenibacterium。此外，一些关键代谢产物[胆汁酸（BA）、生物素和咖啡因]及其相应的代谢途径（主要胆汁酸生物合成，牛磺酸和次牛磺酸代谢，生物素代谢，嘌呤代谢和咖啡因代谢）被B. longum CCFM1077富集，因此可能降低血脂水平。B. longum CCFM1077是一种具有降低高脂血症患者血清TC和LDL-C水平潜力的益生菌菌株。其潜在机制可能与抗肥胖相关属和粪便代谢物的增加有关。这些发现为将来在管理高脂血症患者中应用益生菌奠定了基础。

Abstract

An increasing number of studies have indicated that gut microbiota and its metabolites are crucial in the development of hyperlipidemia. Bifidobacterium longum (B. longum) CCFM1077 has been shown to have lipid-lowering effects in animals. This study aimed to evaluate the potential of B. longum CCFM1077 in lowering the lipid levels in patients with hyperlipidemia and investigate the effect of this bacterium on serum lipid abnormalities, gut microbiota, and fecal metabolites in these patients. This study was a six-week, randomized, double-blind, and placebo-controlled pilot clinical trial. Subjects with hyperlipidemia (N = 62) were randomly assigned to receive placebo (N = 31) or B. longum CCFM1077 (1 × 1010 colony-forming units (CFUs) per day; N = 31). Serum lipid levels including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), total triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) were examined at the baseline and interventional endpoints. Changes in the gut microbiota composition and diversity were measured based on 16S ribosomal RNA (rRNA) sequencing of the V3-V4 region at the end of the intervention period. Non-targeted metabolomics of the feces was performed using ultra-performance liquid chromatography (UPLC)-Q-Exactive Orbitrap/mass spectrometer. Oral administration of B. longum CCFM1077 for six weeks significantly decreased the serum levels of TC (p < 0.01) and LDL-C (p < 0.01) in patients with hyperlipidemia. B. longum CCFM1077 treatment markedly increased gut microbiota diversity and the relative abundance of anti-obesity-related genera, including Lactobacillus, Butyricicoccus, Bifidobacterium, and Blautia, whereas it decreased the relative abundance of obesity-related genera, including Alistipes, Megamonas, and Catenibacterium. Additionally, some key metabolites (bile acids (BAs), biotin, and caffeine) and their corresponding metabolic pathways (primary BA biosynthesis, and taurine and hypotaurine, biotin, purine, and caffeine metabolisms) were enriched by B. longum CCFM1077, and thus it may lower lipid levels. B. longum CCFM1077 is a probiotic strain with the potential to lower serum TC and LDL-C levels patients with hyperlipidemia. The underlying mechanism may be related to the increased abundance of anti-obesity-related genera and fecal metabolites. These findings provide a foundation for future clinical applications of lipid-lowering probiotics in managing individuals with hyperlipidemia.

关键词

益生菌 / 长双歧杆菌 / 高脂血症 / 肠道菌群 / 粪便代谢物 / 胆汁酸

Keywords

Probiotics / Bifidobacterium longum / Hyperlipidemia / Gut microbiota / Fecal metabolites / Bile acid (BA)

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储传奇, 姜金池, 于雷雷. 长双歧杆菌CCFM1077通过调节肠道微生物组成和粪便代谢物来减轻高脂血症——一项随机、双盲、安慰剂对照的临床试验. Engineering. 2023, 28(9): 193-205 https://doi.org/10.1016/j.eng.2023.04.010

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