Circadian influence on the microbiome improves heart failure outcomes

Area of Science:

• Cardiovascular Biology
• Microbiome Research
• Chronobiology

Background:

• Myocardial infarction (MI) leading to heart failure (HF) is a leading global cause of mortality.
• The circadian system and environmental factors like light influence cardiac repair post-MI.
• The gut microbiome's role in cardiac repair and its interaction with the circadian system in HF remain unclear.

Purpose of the Study:

• To investigate the role of gut physiology and the circadian system in cardiac repair following MI.
• To determine if gut microbiome integrity and timing of feeding impact HF outcomes post-MI.

Main Methods:

• Utilized a murine coronary artery ligation model of MI.
• Assessed cardiac repair, inflammatory responses, and HF outcomes in mice with intact or disrupted gut microbiomes.
• Employed circadian mutant mice (Clock^∆19/∆19) and time-restricted feeding protocols.

Main Results:

• Gut microbiome disruption post-MI impaired cardiac repair and worsened HF outcomes.
• Reconstituting the gut microbiome improved cardiac healing.
• A functional circadian system was necessary for the gut microbiome's beneficial effects on cardiac repair.
• Time-restricted feeding during wake times improved HF outcomes, unlike feeding during sleep times.

Conclusions:

• Gut physiology is essential for effective cardiac repair post-MI.
• The circadian system modulates gut-mediated beneficial responses, impacting HF outcomes.
• Circadian regulation of gut responses, influenced by feeding schedules, offers a potential therapeutic avenue for post-MI cardiac repair.