Landscape of gut microbiota and metabolites and their interaction in comorbid heart failure and depressive symptoms: a random forest analysis study

Abstract

ABSTRACT Depression is an individual risk factor for poor prognosis in patients with heart failure (HF). Recent studies show that gut microbiota and metabolites play a critical role in comorbid HF and depressive symptoms. We recruited 95 subjects including 35 HF patients with depressive symptoms (HF-DS), 36 HF patients without depressive symptoms (HF-NDS), and 24 healthy controls (HC). The 16S rRNA, metagenome sequencing, and untargeted metabolomic analysis were employed to test fecal samples. Our analysis found a significant difference in composition of gut microbiota in HF-DS, HF-NDS, and HC populations. At the genus level, Mediterranea , Tolumona , and Parabacteroides were significantly increased in HF-DS patients compared with HF-NDS patients, while Pedobacter , Azospirillum , and Ruminiclostridium were significantly decreased. Furthermore, anti-inflammatory mediators (abietic acid, quinic acid, linoleic acid, etc.) and neurotransmitters (catechin, serotonin, tryptamine, phenylethylamine, etc.) were reduced in HF-DS. The enrichment analysis revealed that the gut microbiota highly conformed to the functional pathways of metabolites, and amino acid-related metabolism, fatty acid-related metabolism, and cAMP signaling pathways may be crucial biological mechanisms involved in the development of comorbid depression and HF. Finally, Cloacibacillus and alpha-tocopherol were determined as diagnostic markers for HF-DS patients. IMPORTANCE There is increasing evidence that alterations in gut microbial composition and function are associated with cardiovascular or psychiatric disease. Therefore, it is meaningful to investigate the taxonomic and functional characterization of the microbiota in HF patients who also have depressive symptoms. In this cross-sectional study, Cloacibacillus and alpha-tocopherol were determined as new diagnostic markers. Furthermore, intestinal microecosystem disorders are closely linked to depressive symptoms in HF patients, providing a new reference viewpoint for understanding the gut-heart/brain axis.