Impact of TAVI on the Gut Microbiota and Its Metabolites

NCT07565077 | Active Not Recruiting

• 1 other identifier: 2023-02339
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Aortic stenosis is a common heart valve disease in older adults. It occurs when the aortic valve becomes narrowed, making it harder for blood to flow from the heart to the rest of the body. Without treatment, this condition can lead to serious complications and reduced survival. A widely used treatment is transcatheter aortic valve implantation (TAVI), a minimally invasive procedure that replaces the diseased valve and improves blood flow. Recent research suggests that heart diseases, including aortic stenosis, may affect the gut (intestinal) environment. The gut contains trillions of microorganisms (called the gut microbiota) that play an important role in digestion, immunity, and overall health. In patients with heart conditions, reduced blood flow may impair the intestinal barrier and alter the balance of these microorganisms. This imbalance may contribute to inflammation and other complications. This study aims to better understand how aortic stenosis and its treatment with TAVI influence the gut microbiota and intestinal health. Researchers will measure specific substances produced by gut bacteria (called metabolites) in blood and stool samples. These include bile acids, trimethylamine N-oxide (TMAO), tryptophan-related compounds, and short-chain fatty acids. Samples will be collected before and three months after the TAVI procedure. In addition, genetic analysis of stool samples will be performed to identify and compare the types of bacteria present before and after treatment. The goal is to determine whether improving heart function with TAVI can restore a healthier gut environment. This may help identify new ways to improve outcomes and reduce complications in patients with aortic stenosis.

Conditions

TAVI; Calcific Aortic Valve Disease; Inflammation; Dysbiosis

Keywords

Gut microbiota; Metabolomics

Outcome Measures

Primary Outcomes (1)

• Change in gut microbiota-derived metabolite levels before and after TAVI

  Quantitative assessment of key gut microbiota-derived metabolites in blood and stool samples, including bile acids (cholic, chenodeoxycholic, deoxycholic, and lithocholic acid), trimethylamine N-oxide (TMAO), tryptophan metabolites, and short-chain fatty acids (SCFAs), measured before and after transcatheter aortic valve implantation (TAVI).

  Baseline (pre-TAVI) and 3 months post-TAVI

Secondary Outcomes (5)

• Change in gut microbiota diversity after TAVI

  Baseline and 3 months post-TAVI

• Change in gut microbiota taxonomic composition after TAVI

  Baseline and 3 months post-TAVI

• Sex-specific differences in gut microbiota changes following TAVI

  Baseline and 3 months post-TAVI

• Association between gut microbiota changes and systemic biomarkers

  Baseline and 3 months post-TAVI

• Prognostic value of gut microbiota and metabolite changes after TAVI

  From baseline to 3 months post-TAVI (and clinical follow-up, if applicable)

Study Arms (1)

Patients with aortic stenosis undergoing TAVI

Patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) as part of routine clinical care. Assessments of gut microbiota composition and metabolomic profiles are performed before the procedure and at 3-month follow-up.

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult patients with severe aortic valve disease referred for transcatheter aortic valve implantation (TAVI) at a single tertiary care center. Patients are enrolled prospectively and undergo evaluation of gut microbiota composition and metabolomic profiles before and after TAVI.

You may qualify if:

• 18 years or older
• Hospitalized for TAVI or investigations before TAVI for significant aortic valve disease
• Severe CAS is defined as: high flow gradient with normal CO (mean gradient ≥40mmHg, Vmax≥4m/s, valve area ≤ 1cm² or ≤0,6cm/m²) or low flow low gradient (mean gradient\<40mmHg, Vmax \<4m/s, valve area ≤ 1cm² or ≤0,6cm/m², stroke volume \< 35ml/m², LVEF\<40%) confirmed by low dose dobutamine echo or high calcium score (\> 1200 in women and \> 2000 in men), paradoxical low-gradient CAS: LVEF \> 55%, Vmax\< 4m/s, mean gradient \< 40mmHg, area \< 1cm²)
• Combined aortic stenosis and aortic regurgitation, considered as severe valvular heart disease with a need for TAVI.
• Written informed consent

You may not qualify if:

• \- Treatment interfering with the composition of the intestinal microbiota: local or systemic corticosteroids within the last 3 months, antibiotics within the last 3 months, antiretrovirals, bile acid chelators (questran and colesevelam), HIV-targeted antiretroviral therapies, selective serotonin reuptake inhibitor-type antidepressants
• Clinical criteria: history of cholecystectomy, documented chronic liver disease in the patient, failure to fast on the day of the blood test, inflammatory bowel disease
• Valve in valve TAVI.
• LVEF \< 20%
• Patients requiring emergency intervention (myocardial infarction, acute aortic or mitral regurgitation, cardiogenic shock).
• AS of rheumatic origin, infective endocarditis.

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead
• Tours university: collaborator

Study Sites (1)

Inselspital, Department of Cardiology

Bern, 3010, Switzerland

Location

Related Publications (7)

• Liao Y, Liu C, Xiong T, Zhao M, Zheng W, Feng Y, Li Y, Ou Y, Zhao Z, Peng Y, Wei J, Li Q, Meng W, Liu X, Chen M. Metabolic Modulation and Potential Biomarkers of the Prognosis Identification for Severe Aortic Stenosis after TAVR by a Metabolomics Study. Cardiol Res Pract. 2020 Oct 28;2020:3946913. doi: 10.1155/2020/3946913. eCollection 2020.

  PMID: 33204525 BACKGROUND

• Li J, Zeng Q, Xiong Z, Xian G, Liu Z, Zhan Q, Lai W, Ao L, Meng X, Ren H, Xu D. Trimethylamine N-oxide induces osteogenic responses in human aortic valve interstitial cells in vitro and aggravates aortic valve lesions in mice. Cardiovasc Res. 2022 Jun 29;118(8):2018-2030. doi: 10.1093/cvr/cvab243.

  PMID: 34352088 BACKGROUND

• Candellier A, Issa N, Grissi M, Brouette T, Avondo C, Gomila C, Blot G, Gubler B, Touati G, Bennis Y, Caus T, Brazier M, Choukroun G, Tribouilloy C, Kamel S, Boudot C, Henaut L; Stop-As Investigators. Indoxyl-sulfate activation of the AhR- NF-kappaB pathway promotes interleukin-6 secretion and the subsequent osteogenic differentiation of human valvular interstitial cells from the aortic valve. J Mol Cell Cardiol. 2023 Jun;179:18-29. doi: 10.1016/j.yjmcc.2023.03.011. Epub 2023 Mar 24.

  PMID: 36967106 BACKGROUND

• Rajamannan NM. Calcific aortic stenosis: lessons learned from experimental and clinical studies. Arterioscler Thromb Vasc Biol. 2009 Feb;29(2):162-8. doi: 10.1161/ATVBAHA.107.156752. Epub 2008 Nov 20.

  PMID: 19023094 BACKGROUND

• Chong Nguyen C, Duboc D, Rainteau D, Sokol H, Humbert L, Seksik P, Bellino A, Abdoul H, Bouazza N, Treluyer JM, Saadi M, Wahbi K, Soliman H, Coffin B, Bado A, Le Gall M, Varenne O, Duboc H. Circulating bile acids concentration is predictive of coronary artery disease in human. Sci Rep. 2021 Nov 22;11(1):22661. doi: 10.1038/s41598-021-02144-y.

  PMID: 34811445 BACKGROUND

• Chong-Nguyen C, Yilmaz B, Coles B, Sokol H, MacPherson A, Siepe M, Reineke D, Mosbahi S, Tomii D, Nakase M, Atighetchi S, Ferro C, Wingert C, Grani C, Pilgrim T, Windecker S, Blasco H, Dupuy C, Emond P, Banz Y, Losmanova T, Doring Y, Siontis GCM. A scoping review evaluating the current state of gut microbiota and its metabolites in valvular heart disease physiopathology. Eur J Clin Invest. 2025 Jun;55(6):e14381. doi: 10.1111/eci.14381. Epub 2025 Jan 10.

  PMID: 39797472 BACKGROUND

• Chong-Nguyen C, Fuentes Artiles R, Pilgrim T, Yilmaz B, Doring Y. The gut-heart axis in coronary artery disease: a scoping and narrative review of sex-based microbial and metabolic disparities. Biol Sex Differ. 2026 Jan 30;17(1):24. doi: 10.1186/s13293-026-00824-w.

  PMID: 41618437 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Stools, valve tissue and Blood (serum)

MeSH Terms

Conditions

Inflammation; Dysbiosis

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2026
• First Posted: May 4, 2026
• Study Start: March 1, 2024
• Primary Completion: February 28, 2026
• Study Completion (Estimated): February 28, 2029
• Last Updated: May 4, 2026

Record last verified: 2026-04

Locations

CH (1)