Impact of sleep fragmentation, heart failure, and their combination, on the gut microbiome

Abstract

Heart failure (HF) is a common condition associated with a high rate of hospitalizations and adverse outcomes. HF is characterized by impairments of the cardiac ventricular filling and/or ejection of blood capacity. Sleep fragmentation (SF) involves a series of short sleep interruptions that lead to fatigue and contribute to cognitive impairments and dementia. Both conditions are known to be associated with increased inflammation and dysbiosis of the gut microbiota. In the present study, male mice were distributed into four groups, and subjected for four weeks to either HF, SF, both HF and SF, or left unperturbed as controls. We used 16S metabarcoding to assess fecal microbiome composition before and after the experiments. Evidence for distinct alterations in several bacterial groups and an overall decrease in alpha diversity emerged in HF and SF treatment groups. Combined HF and SF conditions, however, showed no synergism, and observed changes were not always additive, suggesting that some of the individual effects of either HF or SF cancel each other out when applied concomitantly.IMPORTANCEThe study demonstrates the potential of the gut microbiome as a source of molecular markers for the diagnosis, prevention, and treatment of both heart failure and sleep fragmentation conditions in isolation. Our results provide the first evidence of an antagonistic effect of the presence of both conditions in the gut microbiome dysbiosis, showing an attenuation of the alterations that are observed when considering them separately.

Lifelong dietary omega-3 fatty acid suppresses thrombotic potential through gut microbiota alteration in aged mice

“…In similar analyses, the genus Peptococcaceae , identified to both negatively contribute to TMAO levels and in vivo clot formation, was remarkably decreased in old mice versus young mice ( Zhu et al., 2016 ). As shown in Figure 2 B, aging was associated with a significant increase in the proportions of Desulfovibrio , known for producing trimethylamine (TMA), a precursor of TMAO ( Zeisel and Warrier, 2017 ), and for modulating the production of proinflammatory cytokines ( Zhang-Sun et al., 2015 ), and of genera Ileibacterium , in particular I. valens , a genus which is highly abundant in the intestinal microbiota of mice with heart failure ( Khannous-Lleiffe et al., 2020 ). In line, these taxonomic shifts were accompanied by age-dependent alteration in microbiota-derived metabolites levels, so that age is known to be both significantly positively associated with plasma TMAO levels (p < 0.0001, Figure 2 C) and negatively associated with fecal levels of SCFAs, acetate, and propionate, seen in old versus young mice (for both p < 0.0001, Figures 2 D and 2E).…”