A newly published multi-omics study has linked chronic systolic heart failure to measurable changes in the gut microbiome, including a marked depletion of Bifidobacterium. Among patients followed over time, higher levels of these bacteria were also associated with clinical improvement.
The research, published in Nature Cardiovascular Research on 24 September 2026, compared 59 adults with chronic systolic heart failure caused by nonischemic cardiomyopathy with 50 healthy participants. Researchers combined stool metagenomics with blood metabolomics, lipidomics, immune profiling and detailed clinical measurements.
The gut microbiome differed in heart failure
Patients with heart failure had lower gut microbial alpha diversity, while overall microbial community composition also differed significantly from healthy participants. The between-group difference in beta diversity was statistically significant at P = 0.001.
Differential abundance analysis identified depletion of the bacterial families Lachnospiraceae and Bifidobacteriaceae and several genera, including Bifidobacterium, Anaerostipes, Anaerobutyricum, Lachnospira and Blautia. For these comparisons, adjusted P values were below 0.001.
Many of the depleted organisms are associated with production of short-chain fatty acids from dietary fibre and with anti-inflammatory effects. The researchers also found reduced microbial potential for producing these metabolites in the heart failure group.
Bifidobacterium tracked improvement over time
The longitudinal part of the study provided an additional clue. Twenty-six patients returned for repeat profiling after an average of six months. Six improved by at least one New York Heart Association functional class, while 20 remained stable or worsened.
Bifidobacterium was more abundant at baseline and increased over time among patients whose functional status improved. Three species were associated with improvement in functional class: Bifidobacterium longum, Bifidobacterium breve and Bifidobacterium pseudocatenulatum. Their nominal P values were 0.013, 0.014 and 0.018 respectively, with an adjusted P value of 0.024 for each.
The researchers therefore describe Bifidobacterium as a candidate biomarker of heart failure improvement, rather than evidence that taking a probiotic would improve heart failure.
A microbial metabolite emerged as another clue
By integrating microbiome and host data, the team identified indole-3-propionic acid, or IPA, as a potential link between gut bacteria and heart health. Laboratory experiments confirmed that Bifidobacterium species could produce IPA, while higher circulating IPA concentrations in participants were associated with milder heart failure.
This does not establish that IPA or Bifidobacterium causes clinical improvement. Instead, the results provide biological candidates that can now be tested more directly in larger cohorts and intervention studies.
Why the findings matter
Heart failure can progress very differently between patients even when they receive appropriate treatment. Identifying biological signals associated with severity or improvement could eventually help researchers understand why those trajectories diverge.
The study is notable because it did not examine the microbiome in isolation. It combined microbial DNA sequencing with metabolites, lipids, inflammatory markers and clinical outcomes, allowing researchers to identify connections across several biological systems.
Important limitations
The study was observational and cannot establish that the microbiome changes caused heart failure severity or recovery. The heart failure cohort was relatively small, and only 26 patients completed the six-month repeat profiling. Women were also underrepresented in the heart failure group, accounting for 22% of that cohort compared with 52% of the healthy comparison group.
Stool collection methods differed between the heart failure and healthy groups, although the researchers reported no substantial batch effect and repeated key comparisons using an additional validation cohort. The findings also apply specifically to chronic systolic heart failure associated with nonischemic cardiomyopathy and should not automatically be generalised to every form of heart failure.
Most importantly, the study does not show that probiotic supplements or dietary changes can treat heart failure. Clinical trials would be required before microbiome-targeted interventions could be recommended.
Source Information
Study: Gut microbiome shifts in chronic systolic heart failure are associated with disease severity and clinical improvement
Authors: Petra Mamic, Handuo Shi, Wenyu Zhou and colleagues
Journal: Nature Cardiovascular Research
Published: 24 September 2026
DOI: 10.1038/s44161-026-00854-y
Study design: Integrated microbiome and host multi-omics study with longitudinal follow-up in a subset
Participants: 59 adults with chronic systolic heart failure due to nonischemic cardiomyopathy and 50 healthy participants; 26 heart failure patients completed repeat profiling after an average of six months
