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黑加仑通过肠-骨轴改变肠道微生物群组成并降低绝经后骨质疏松症风险:来自一项先导随机对照试验的证据。

Blackcurrants shape gut microbiota profile and reduce risk of postmenopausal osteoporosis via the gut-bone axis: Evidence from a pilot randomized controlled trial.

机构信息

Department of Nutritional Sciences, University of Connecticut, Storrs, CT.

Department of Kinesiology, University of Connecticut, Storrs, CT.

出版信息

J Nutr Biochem. 2024 Nov;133:109701. doi: 10.1016/j.jnutbio.2024.109701. Epub 2024 Jul 15.

DOI:10.1016/j.jnutbio.2024.109701
PMID:39019119
Abstract

This study aimed to investigate the effects of blackcurrant (BC) on gut microbiota abundance and composition, inflammatory and immune responses, and their relationship with bone mass changes. The effects of BC on bone mineral density (BMD), gut microbiota, and blood inflammatory and immune biomarkers were evaluated using DXA, stool and fasting blood collected from a pilot three-arm, randomized, double-blind, placebo-controlled clinical trial. Fifty-one peri- and early postmenopausal women aged 45-60 years were randomly assigned into one of three treatment groups for 6 months: control, low BC (392 mg/day) and high BC (784 mg/day); and 40 women completed the trial. BC supplementation for 6 months effectively mitigated the loss of whole-body BMD (P<.05). Six-month changes (%) in peripheral IL-1β (P=.056) and RANKL (P=.052) for the high BC group were marginally significantly lower than the control group. Six-month changes in whole-body BMD were inversely correlated with changes in RANKL (P<.01). In proteome analysis, four plasma proteins showed increased expression in the high BC group: IGFBP4, tetranectin, fetuin-B, and vitamin K-dependent protein S. BC dose-dependently increased the relative abundance of Ruminococcus 2 (P<.05), one of six bacteria correlated with BMD changes in the high BC group (P<.05), suggesting it might be the key bacteria that drove bone protective effects. Daily BC consumption for 6 months mitigated bone loss in this population potentially through modulating the gut microbiota composition and suppressing osteoclastogenic cytokines. Larger-scale clinical trials on the potential benefits of BC and connection of Ruminococcus 2 with BMD maintenance in postmenopausal women are warranted. Trial Registration: NCT04431960, https://classic.clinicaltrials.gov/ct2/show/NCT04431960.

摘要

本研究旨在探讨黑加仑(BC)对肠道微生物群落丰度和组成、炎症和免疫反应的影响,以及它们与骨量变化的关系。使用 DXA、粪便和空腹血样,从一项三臂、随机、双盲、安慰剂对照的临床试验中评估了 BC 对骨密度(BMD)、肠道微生物群和血液炎症及免疫生物标志物的影响。51 名年龄在 45-60 岁的绝经前期和早期绝经后妇女被随机分配到三个治疗组中的一个,接受为期 6 个月的治疗:对照组、低 BC(392mg/天)和高 BC(784mg/天);40 名妇女完成了试验。BC 补充 6 个月可有效减轻全身 BMD 的丢失(P<.05)。高 BC 组外周白细胞介素-1β(IL-1β)(P=.056)和核因子-κB 受体活化因子配体(RANKL)(P=.052)的 6 个月变化与对照组相比略有显著降低。全身 BMD 的 6 个月变化与 RANKL 的变化呈负相关(P<.01)。在蛋白质组分析中,高 BC 组有 4 种血浆蛋白表达增加:胰岛素样生长因子结合蛋白 4(IGFBP4)、四连接蛋白、胎球蛋白-B 和维生素 K 依赖性蛋白 S。BC 剂量依赖性地增加了 Ruminococcus 2 的相对丰度(P<.05),这是与高 BC 组 BMD 变化相关的六种细菌之一(P<.05),提示其可能是驱动骨保护作用的关键细菌。6 个月的每日 BC 摄入可减轻该人群的骨丢失,可能是通过调节肠道微生物群落组成和抑制破骨细胞生成细胞因子。需要更大规模的临床试验来评估 BC 的潜在益处以及 Ruminococcus 2 与绝经后妇女 BMD 维持的关系。试验注册:NCT04431960,https://classic.clinicaltrials.gov/ct2/show/NCT04431960。

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