the Gut Microbiome and Metabolomics in Chronic Lower extreMities Threatening Ischemia

N/AUnknownNCT06220994

Beijing Tsinghua Chang Gung Hospital120 enrolled

Overview

Intestinal floras and their metabolites are involved in progressing metabolic and cardiovascular diseases. However, currently, articles related to the relationship between intestinal floras and atherosclerosis mainly focus on coronary atherosclerotic disease (CAD) population, or atherosclerosis model animals such as ApoE-/-, LDLR-/- high-fat diet mice, and there are few studies on Chronic limb-threatening ischemia (CLTI). CLTI and CAD have a similar pathological basis of atherosclerosis. It is unclear whether intestinal flora plays an essential role in the occurrence and development of CLTI. This project aims to explore the relation between microorganisms, metabolites, and CLTI.

This project aims to study the intestinal flora and its metabolites in patients with CLTI, explore whether CLTI patients and CAD patients have their own characteristic flora, analyze the microorganisms and metabolites markers of poor prognosis in patients with CLTI, and screen out the key differential bacteria and metabolites that inhibit the progress of CLTI, in order to provide new insights and research basis for the treatment of CLTI.

Study Type

OBSERVATIONAL

Enrollment

120

Conditions

Chronic Limb-threatening Ischemia Microtia

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: Control group: sex - and age-matched healthy people (without history of atherosclerotic plaque, coronary heart disease or stroke). Case group: resting pain for at least 2 weeks with at least one hemodynamic index: ABI\<0.4,AP\<50mmHg, TP or TCPO2\<30mmHg. Tissue defects (ulceration or gangrene) persisted for at least 2 weeks with at least one significant PAD objective evidence: ABI\<0.8, AP\<100mmHg, TP or TCPO2\<60mmHg. Exclusion Criteria: 1. Patients with inflammatory bowel disease, autoimmune diseases, malignancies, infectious diseases, and severe liver and kidney dysfunction (cirrhosis, CKD stage 4 and 5). 2. Patients with thromboembolic angiitis, arterial embolism, and takayasu. 3. Patients who have used probiotics or antibiotics in the last 2 months. 4. After interventional surgery and amputation below the knee or above knee.

Outcomes

Primary Outcomes

Bacteria or metabolites associated with prolonged survival time without above-knee amputation

The relationship between the prognosis and gut microbiota or plasma metabolomics was analyzed. Spearman correlations between CAGs, serum metabolite modules and clinical parameters were calculated using R, and both differential abundances of CAGs and CLTI-associated metabotypes were tested by the Wilcoxon rank sum test.

Time frame: 3years.

Secondary Outcomes

Key bacteria in CLTI

Differential bacteria enriched in healthy group but absent in CLTI patients were explored by metagenomic analysis of the gut microbiota. It includes species composition and abundance analysis, beta diversity, differences between groups, and RDA/CCA.

Time frame: up to 1 week

Key plasma metabolites in CLTI

Differential metabolites enriched in healthy group but absent in CLTI patients were explored by non-targeted metabolomics analysis of the gut contents. It includes sample grouping data analysis, metabolites annotation, and screening of differential metabolites.