Multi-omic study links gut bacteria to heart failure progression
- A multi-omic study published in the journal Nature Cardiovascular Research links gut bacteria, microbial metabolites, and changes in heart function, pointing to biological relationships that could reshape how...
- The mechanisms driving this disease progression remain poorly understood.
- To investigate the connection between the gut microbiome and chronic systolic heart failure outcomes, investigators utilized host multi-omic profiling alongside microbiome analysis.
A multi-omic study published in the journal Nature Cardiovascular Research links gut bacteria, microbial metabolites, and changes in heart function, pointing to biological relationships that could reshape how researchers investigate heart failure progression. Chronic systolic heart failure due to nonischemic cardiomyopathy presents considerable morbidity and an increased risk of death.
Gut Bacteria Linked to Heart Failure Progression
The mechanisms driving this disease progression remain poorly understood.
To investigate the connection between the gut microbiome and chronic systolic heart failure outcomes, investigators utilized host multi-omic profiling alongside microbiome analysis. Stool samples underwent metagenomic sequencing to reveal gut microbiome composition, while microbial shifts tied to heart failure were pinpointed using differential abundance analysis.
Metabolomics assessed microbiome-derived metabolites, and gene set enrichment analysis identified heart failure-associated functional groups.
Strict Patient Selection Criteria
The study population comprised 59 adults with chronic heart failure due to nonischemic cardiomyopathy, enrolled between July 2018 and March 2020. They were joined by 50 healthy participants from the existing integrated Personal Omics Profiling study.
The investigation excluded individuals with primary ischemic cardiomyopathy, complex congenital heart disease, treated diabetes, advanced kidney or liver disease, autoimmune disorders, active malignancies, or recent abdominal surgery.
Recent use of probiotics, antibiotics, radiation, or chemotherapy was also cause for exclusion.
Depleted Anti-Inflammatory Microbes
In the guts of heart failure patients, alpha diversity and anti-inflammatory microbes, including Bifidobacterium and short-chain fatty acid-producing microbes, were depleted compared to healthy controls. Patients also showed lower levels of the Lachnospiraceae family and the Anaerobutyricum, Anaerostipes, Blautia, and Lachnospira genera.
Conversely, the genera Prevotella and Sutterella, which have been linked to pro-inflammatory host responses, were enriched among heart failure patients.
Downregulated Metabolic Pathways
Functional analysis demonstrated that pathways associated with short-chain fatty acid, methane, and L-arginine production, as well as formaldehyde detoxification, were downregulated in heart failure patients. Researchers also observed an enrichment of pathways involved in pro-inflammatory lipopolysaccharide generation.
Altered L-arginine and ornithine pathways were linked to different microbiome-immune interactions in heart failure, though the study did not establish that changes in the microbiome directly altered their systemic production.
Microbial Abundance and Milder Disease
The findings indicate that Bifidobacterium, some strains of which produced indole-3-propionic acid in laboratory experiments, may play a functional role in heart failure. Greater Bifidobacterium abundance was associated with milder disease and improved functional status.
Higher circulating indole-3-propionic acid and predicted microbial butyrate production were also associated with milder heart failure measures.
Longitudinal Tracking of Clinical Trajectories
Longitudinal analyses tracked a subset of patients over time to evaluate clinical trajectories. Twenty-six heart failure patients returned for repeat multi-omic profiling and clinical assessment after an average of six months, while longer-term clinical follow-up data were obtained for 51 patients after an average of 27 months.
Clinical outcomes were assessed based on heart transplantation, placement of a left ventricular assist device, hospice care, or death.
Clinical improvement was determined using the Kansas City Cardiomyopathy Questionnaire, New York Heart Association functional classes, and left ventricular ejection fraction.