| Summary: | In this study, we investigated the effect of three different probiotics, namely, a combination of <i>Lactobacillus acidophilus (LA–5)</i> and <i>Bifidobacterium animalis</i> subsp. <i>lactis (BB–12)</i>, <i>Saccharomyces boulardii</i>, and <i>Enterococcus faecium L3</i> on myocardial infarct size in rats with diet-induced obesity (DIO) and chemically-induced colitis (CIC). Potential associations between the effects of probiotics on myocardial ischemia-reperfusion injury and gut microbiome patterns as well as the serum levels of pro- and anti-inflammatory cytokines, lipopolysaccharide, and short chain fatty acids were also studied. Intragastric administration of lyophilized <i>Lactobacillus acidophilus</i> and <i>Bifidobacterium animalis</i> subsp. <i>lactis</i> at a dose of 1.2 × 10<sup>8</sup> CFU/mL for 15 days resulted in myocardial infarct size reduction in rats with DIO, CIC, and antibiotic-induced dysbiosis. This cardioprotective effect was associated with specific changes in cytokine concentrations, namely reduced levels of IL–1β, TNF–α, IL–2, and IL–8. At the same time, the use of <i>Lactobacillus acidophilus</i> and <i>Bifidobacterium animalis</i> subsp. <i>lactis</i> was accompanied by a significant reduction in lipopolysaccharide level, suggesting normalization of intestinal epithelial barrier permeability. However, the cardioprotective effect of <i>Lactobacillus acidophilus</i> and <i>Bifidobacterium animalis</i> subsp. <i>lactis</i> is not secondary to improved healing of the intestinal mucosa in CIC, as evidenced by the lack of difference in histopathological scores.
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