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 microbiome interventions can attenuate myocardial ischemia-reperfusion injury (IRI) in diabetic hearts remains unclear. Therefore, we tested whether fecal microbiota transplantation (FMT) from lean non-diabetic donors could mitigate myocardial IRI in type 2 diabetes mellitus (T2DM) db/db mice and explored candidate taxa associated with protection. METHODS: Male db/db mice (T2DM 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 LEfSe further suggested Akkermansia, particularly Akkermansia 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. Akkermansia muciniphila emerged as a candidate taxon associated with a reduced susceptibility to IRI in diabetic hearts.