肌肉骨骼问题老年人的试验：因潜在的肌肉减少症导致的粪便来揭示肠道和炎症转化（匆匆过客）：一项探索社区居住的老年人肌肉减少症发生和治疗中肠道-肌肉轴的横断面研究方案。

Trial in Elderly with Musculoskeletal Problems due to Underlying Sarcopenia-Faeces to Unravel the Gut and Inflammation Translationally (TEMPUS-FUGIT): protocol of a cross-sequential study to explore the gut-muscle axis in the development and treatment of sarcopenia in community-dwelling older adults.

机构信息

Department of Public Health and Primary Care, Division of Gerontology and Geriatrics, KU Leuven, Herestraat 49, Leuven, 3000, Belgium.

Department of Geriatric Medicine, UZ Leuven, Leuven, Belgium.

出版信息

BMC Geriatr. 2023 Sep 26;23(1):599. doi: 10.1186/s12877-023-04291-5.

DOI:10.1186/s12877-023-04291-5

PMID:37752426

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10523729/

Abstract

BACKGROUND

Gut microbiota (GM) might play a role in muscle metabolism and physiological processes through a hypothesized gut-muscle axis, influencing muscle mass and function and thus, sarcopenia. The Trial in Elderly with Musculoskeletal Problems due to Underlying Sarcopenia-Faeces to Unravel the Gut and Inflammation Translationally (TEMPUS-FUGIT) aims to explore the gut-muscle axis in sarcopenia.

METHODS

First, in a cross-sectional case-control phase, 100 community-dwelling adults without sarcopenia will be compared to 100 community-dwelling adults (≥ 65 years) with sarcopenia of similar age-, gender and BMI-ratio, participating in the ongoing 'Exercise and Nutrition for Healthy AgeiNg' (ENHANce; NCT03649698) study. Sarcopenia is diagnosed according to the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria. GM composition and intestinal inflammatory markers (fecal calprotectin, lactoferrin and S100A12) will be determined in fecal samples. Systemic inflammatory markers (hs-CRP, IL-4, IL-6, TNF-α, IL-13, IL-1β and creatine kinase) will be determined in fasted blood samples. Both groups will be compared using appropriate statistical testing, whereas linear regression will be used for cross-sectional associations between gut, inflammatory and sarcopenia parameters. Second, in the longitudinal phase, sarcopenic older adults will be requested to deliver five fecal samples during the 12-week intervention to assess the effects of protein, omega-3 and a physical exercise program on the GM.

DISCUSSION

TEMPUS-FUGIT aims to explore the gut-muscle axis by comparing GM composition between sarcopenic and non-sarcopenic older adults and to determine the association of GM with intestinal and systemic inflammatory markers and sarcopenia-defining parameters (muscle mass, muscle strength and physical performance). Furthermore, effects of single or combined, optimized and individualized anabolic interventions (exercise, protein and omega-3 supplementation), on GM will be explored in persons with sarcopenia. TEMPUS-FUGIT aims to impact clinical practice by clarifying the relationship between the gut-muscle axis and sarcopenia. TEMPUS-FUGIT is expected to contribute to the discovery of clinical and microbial biomarkers for sarcopenia and insights in its pathophysiology, opening possible future perspectives for novel sarcopenia treatment strategies targeting GM.

TRIAL REGISTRATION

ClinicalTrails.gov NCT05008770, registered on August 17, 2021; first participant enrolled on September 21 2021.

摘要

背景

肠道微生物群（GM）可能通过假设的肠道-肌肉轴在肌肉代谢和生理过程中发挥作用，影响肌肉质量和功能，从而影响肌肉减少症。因潜在的肌肉减少症导致肌肉骨骼问题的老年人试验-粪便阐明肠道和炎症的转化（TEMPUS-FUGIT）旨在探索肌肉减少症中的肠道-肌肉轴。

方法

首先，在横断面病例对照阶段，将 100 名无肌肉减少症的社区居住成年人与 100 名年龄、性别和 BMI 比例相似的社区居住的肌肉减少症成年人（≥65 岁）进行比较，他们正在参加正在进行的“运动和营养促进健康老龄化”（ENHANce；NCT03649698）研究。根据欧洲老年人肌肉减少症工作组 2（EWGSOP2）标准诊断肌肉减少症。将在粪便样本中确定 GM 组成和肠道炎症标志物（粪便钙卫蛋白、乳铁蛋白和 S100A12）。将在禁食血液样本中确定系统炎症标志物（hs-CRP、IL-4、IL-6、TNF-α、IL-13、IL-1β 和肌酸激酶）。使用适当的统计检验比较两组，而线性回归将用于肠道、炎症和肌肉减少症参数之间的横断面关联。其次，在纵向阶段，要求肌肉减少症老年人在 12 周干预期间提供 5 份粪便样本，以评估蛋白质、欧米伽 3 和体育锻炼计划对 GM 的影响。

讨论

TEMPUS-FUGIT 通过比较肌肉减少症和非肌肉减少症老年人之间的 GM 组成，旨在探索肠道-肌肉轴，并确定 GM 与肠道和系统炎症标志物以及肌肉减少症定义参数（肌肉质量、肌肉力量和身体表现）之间的关联。此外，还将探讨单一或联合、优化和个体化的合成代谢干预（运动、蛋白质和欧米伽 3 补充）对肌肉减少症患者 GM 的影响。TEMPUS-FUGIT 旨在通过阐明肠道-肌肉轴与肌肉减少症之间的关系来影响临床实践。TEMPUS-FUGIT 有望为肌肉减少症的临床和微生物生物标志物以及对其病理生理学的深入了解做出贡献，为针对 GM 的新型肌肉减少症治疗策略开辟可能的未来前景。