Short Chain Fatty Acids Profiles in Amyotrophic Lateral Sclerosis: Longitudinal Effects of Disease and Mediterranean Diet Intervention
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Analysis of serum SCFA levels in ALS patients and healthy controls, and evaluating the change in circulating SCFA concentrations associated with Mediterranean diet intervention
研究概览
简要总结
This observational study explored the connection between the gut microbiota and the brain in patients with amyotrophic lateral sclerosis (ALS), specifically the modulation of short-chain fatty acids during disease progression and after following a Mediterranean diet for 6 months. Recent research suggests that the gut microbiome-the community of bacteria and other microorganisms living in our intestines-may influence how ALS develops and progresses. The hypothesis was that changes in the gut microbiome and the substances it produces, such as short-chain fatty acids (SCFAs), may play an important role in ALS progression. Additionally, the effect of the Mediterranean diet on circulating short-chain fatty acid concentrations was assessed.
详细描述
This study investigates the role of the microbiome-gut-brain axis in the progression of amyotrophic lateral sclerosis (ALS), with a focus on short-chain fatty acids (SCFAs) and their associated biomarker panel (SCFAGGYC-PROF). The investigators hypothesized that alterations in the gut microbiota composition and SCFA metabolism contribute to the heterogeneity of ALS phenotypes, influencing whether the disease follows a rapidly progressive or more slowly progressive course.
Participants with ALS and healthy controls undergo blood sampling and stool collection at baseline and follow-up. Serum analyses include: measurement of circulating SCFA levels using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
In a subset of ALS patients, dietary interventions consistent with a Mediterranean dietary pattern are introduced to evaluate the impact of nutrition on gut microbiota composition, SCFA production, and clinical disease progression. This 12-month study (6 months natural course + 6 months dietary intervention) evaluated Mediterranean diet effects on ALS progression rate and circulating levels of SCFA. The diet-known for neuroprotective and anti-inflammatory properties-was associated with significant changes in SCFA plasma levels.
A key process stage involved developing and applying an LC-MS/MS method for plasma quantification of acetic (C2), propionic (C3), butyric (C4), 3-hydroxybutyric (3-OH-C4), hexanoic (C6), and iso-hexanoic acid (Iso-C6; 4-methyl-valeric), using acetic acid-C13, butyric-d8 and hexanoic-d11 as internal standards.
After extraction and derivatization of analytes from plasma, samples were analyzed by reversed-phase LC and detected via MS/MS in MRM mode with negative ESI. The method enabled quantitative determination of free plasma carboxylic acids.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patients diagnosed with amyotrophic lateral sclerosis (ALS) in the past 12 months.
- •Disease duration of less than 1 year.
- •Fulfillment of the El Escorial diagnostic criteria (1996) for clinically probable or clinically definite ALS.
排除标准
- •Patients with an expected survival <18 months.
- •Presence of other neurodegenerative diseases.
- •Major comorbidities, such as: heart failure, cancer, autoimmune diseases, systemic diseases.
- •Gastrointestinal diseases that could influence gut microbiota.
- •Recent or ongoing treatment with antibiotics, probiotics, or prebiotics.
- •Low compliance with study procedures.
结局指标
主要结局
Analysis of serum SCFA levels in ALS patients and healthy controls, and evaluating the change in circulating SCFA concentrations associated with Mediterranean diet intervention
时间窗: 12 months
This study compares plasma levels of short-chain fatty acids (SCFAs): acetic acid (ng/mL), propanoic acid (ng/mL), butyric acid (ng/mL), 3-OH butyric acid, 4-methyl-valeric acid (ng/mL) between adults with amyotrophic lateral sclerosis (ALS) and age/sex-matched healthy controls at baseline (T0) and then tracks how these levels change after 6 months of natural disease progression (T1) and 6 months after introducing a Mediterranean diet (T2) in ALS patients. Outcomes: Mean SCFA concentrations (±SD) (ng/mL) at T0 between-group (ALS vs control) differences at baseline, and within-patient changes over time to assess whether the Mediterranean diet is associated with favorable SCFA shifts (T0-T1, T1-T2).
次要结局
- Association of Serum SCFA Levels With ALS Progression Measured by ALSFRS-R at T0, T1, and T2(12 months)
研究者
Motataianu Anca
Associate Professor
George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures