Abstract P497: Myocardial Infarct Outcome And Weight Gain In Menopause Mice Are Mitigated During Probiotic Oligofructose Treatment

Abstract

The average woman spends over 40% of their life in menopause, during which estrogen’s protective roles are lost and women suffer an increased risk of developing inflammatory pathologies including obesity and worsened cardiovascular disease outcomes. Yet, safe, and effective menopause therapies are still unavailable. The gut microbiome impacts both metabolic and circulating estrogen homeostasis. A dysbiotic (unhealthy) gut can contribute to pathologies that are also observed during menopause including increased obesity and worsened myocardial infarct (MI) outcomes. We have previously demonstrated that gut manipulation through prebiotics (Oligofructose [OFS]), attenuates myocardial infarct injury, improved glucose tolerance, and reduced weight gain in mice. We hypothesize that loss of estrogen during menopause results in intestine morphological and microbial changes, worsens MI outcomes and increases weight gain, which can be mitigated with OFS treatment. Menopause was induced in female mice fed a high-fat-diet (HFD, 45% fat) via 4-vinylcycohexane diepoxide intraperitoneal injections (controls were injected with sesame oil), menopause (14+days diestrus) was determined by cytology. Following menopause, mice were treated for 6wks with 10% OFS supplemented into the diet (provided ad libitum; controls were fed HFD food only). Mice underwent 3day permanent ligation prior to sacrifice. We observed that menopause results in increased villi density in the duodenum and ileum, and that menopausal mice had a significant increase in both duodenum villi length and wall thickness. Menopause was associated with a shift in the gut microbiota composition. Relative abundance of Alistipes was reduced in menopausal mice, compared to premenopausal mice, and is restored with OFS treatment. Furthermore, menopausal mice had increased weight gain and infarct size compared to premenopausal mice, and OFS attenuated the differences between menopause and perimenopause weight gain over time and infarct size. Together these data demonstrate menopause is associated with intestinal morphological changes and shifts in the gut microbiome, and that in the presence of OFS infarct size and weight gain in menopausal mice are mitigated.