Gut Microbiota Modulation Attenuates Myocardial Ischemia-Reperfusion Injury in Diabetic Mice.

BACKGROUND

The gut microbiome is increasingly being recognized as a regulator of cardiometabolic health; however, whether the microbiome interventions can attenuate myocardial ischemia-reperfusion injury (IRI) in diabetic hearts remains unclear. Therefore, we tested whether fecal microbiota transplantation (FMT) from lean nondiabetic donors could mitigate myocardial IRI in type 2 diabetes mellitus db/db mice and explored candidate taxa associated with protection.

METHODS

Male db/db mice (type 2 diabetes mellitus model) received a 14-day course of FMT from lean db/m donors or a vehicle after antibiotic pretreatment. Myocardial IRI was induced, and infarct size was quantified. The gut microbiota was evaluated by 16S rRNA gene sequencing.

RESULTS

FMT significantly reduced the infarct size as a percentage of the area at risk compared to the IRI group (38.7 ± 13.4% vs. 58.7 ± 4.3%, P = 0.003). Microbiome analysis revealed that among alpha-diversity metrics, only the Simpson index differed between the donor and diabetic groups. In beta-diversity analyses, diabetic mice clustered separately from donor mice, and the microbiome intervention induced a modest but significant shift detected by the presence or absence of Unweighted UniFrac. Differential abundance analysis and exploratory linear discriminant analysis effect size further suggested Akkermansia , particularly A. muciniphila , as a candidate taxon reduced in diabetic mice and partially restored after the FMT intervention.

CONCLUSION

A donor-derived microbiome intervention attenuated myocardial IRI in db/db mice and was accompanied by partial remodeling of the gut microbiota. A. muciniphila emerged as a candidate taxon associated with a reduced susceptibility to IRI in diabetic hearts.