Lactobacillus gasseri prevents ibrutinib-associated atrial fibrillation through butyrate.

2025-01-17
Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology 27(2)

PubMed: 39821305
DOI: 10.1093/europace/euaf018

Study Design

Population: rats
Methods: Utilizing 16S rRNA gene sequencing, faecal microbiota transplantation, metabonomics, electrophysiological examination, and molecular biology methodologies

Animal Study

Background

Ibrutinib, a widely used anti-cancer drug, is known to significantly increase the susceptibility to atrial fibrillation (AF). While it is recognized that drugs can reshape the gut microbiota, influencing both therapeutic effectiveness and adverse events, the role of gut microbiota in ibrutinib-induced AF remains largely unexplored.

Method

Utilizing 16S rRNA gene sequencing, faecal microbiota transplantation, metabonomics, electrophysiological examination, and molecular biology methodologies, we sought to validate the hypothesis that gut microbiota dysbiosis promotes ibrutinib-associated AF and to elucidate the underlying mechanisms.

Result

We found that ibrutinib administration pre-disposes rats to AF. Interestingly, ibrutinib-associated microbial transplantation conferred increased susceptibility to AF in rats. Notably, ibrutinib induced a significantly decrease in the abundance of Lactobacillus gasseri (L. gasseri), and oral supplementation of L. gasseri or its metabolite, butyrate (BA), effectively prevented rats from ibrutinib-induced AF. Mechanistically, BA inhibits the generation of reactive oxygen species, thereby ameliorating atrial structural remodelling. Furthermore, we demonstrated that ibrutinib inhibited the growth of L. gasseri by disrupting the intestinal barrier integrity.

Conclusion

Collectively, our findings provide compelling experimental evidence supporting the potential efficacy of targeting gut microbes in preventing ibrutinib-associated AF, opening new avenues for therapeutic interventions.

Research Insights

Supplement	Dose	Health Outcome	Effect Type	Effect Size	Source
Lactobacillus gasseri LG-36	—	Reduced Atrial Fibrillation Risk	Beneficial	Moderate	View source oral supplementation of L. gasseri or its metabolite, butyrate (BA), effectively prevented rats from ibrutinib-induced AF.
Lactobacillus gasseri LG-36	—	Reduced Oxidative Stress	Beneficial	Moderate	View source BA inhibits the generation of reactive oxygen species, thereby ameliorating atrial structural remodelling.