Sex differences in the intestinal microbiome: interactions with risk factors for atherosclerosis and cardiovascular disease

Abstract

Background There are clearly sex differences in cardiovascular disease. On average, women experience cardiovascular events at an older age, and at any age, women, on average, have less atherosclerotic plaque than men. The role of the human intestinal microbiome in health and disease has garnered significant interest in recent years, and there have been indications of sex differences in the intestinal microbiome. The purpose of this narrative review was to evaluate evidence of sex differences in the interaction between the intestinal microbiome and risk factors for cardiovascular disease. Several studies have demonstrated changes in microbiota composition and metabolic profile as a function of diet, sex hormones, and host metabolism, among other factors. This dysbiosis has consequently been associated with several disease states, including atherosclerosis and cardiovascular disease. In this respect, there is a growing appreciation for the microbiota and its secreted metabolites, including trimethylamine N-oxide (TMAO), derived from intestinal bacterial metabolic pathways involving dietary choline and l-carnitine, as novel risk factors for atherosclerosis and cardiovascular outcomes. Although traditional risk factors for vascular disease have been studied broadly over the years, there exists little research to evaluate interactions of cardiovascular risk factors with a potentially sexually dimorphic intestinal microbiome. This review evaluates the role of sex differences in the composition of the intestinal microbiome, including effects of sex hormones on the microbiome, and the effects of these sex differences on cardiovascular risk factors. Diabetes and obesity exhibit sexual dimorphism, while the data concerning hypertension and dyslipidemia remain inconclusive based on the available literature. In addition, an increased proportion of gram-negative species capable of driving metabolic endotoxemia and a low-grade inflammatory response, as well as decreased numbers of butyrate-producing species, have been observed in relation to traditional vascular risk factors. In this context, circulating SCFAs and TMAO are recognized as key metabolites of the intestinal microbiome that can be readily measured in the blood for the evaluation of metabolic profile. Conclusion Novel strategies focused on resolving intestinal dysbiosis as a means to slow progression of atherosclerosis and reduce the risk of cardiovascular disease should be evaluated through a lens of sex differences.

Sex and gender differences in community-acquired pneumonia

“…A similar pattern has been observed for the gut microbiota, which also influences immune responses in the lung [ 27 ]. Sex-related differences have been found in gut microbiota’s composition [ 28 ], its influence on the immunity system [ 29 ], and its interaction with risk factors for several diseases [ 30 ]. Therefore, it seems reasonable to infer that similar sex-related differences exist in lung microbiota as well, being perhaps one factor associated with the lower CAP incidence in women; however, this relationship has not been adequately elucidated yet.…”

Different gender-derived gut microbiota influence stroke outcomes by mitigating inflammation

“…This male predominance persists in ischemic stroke subtypes or stratification by other etiologies [28][29][30]. Clinical and experimental evidence [31,32] shows that natural sex bias in the gut microbiota also exists, which may be due to the influence of sex hormones. Estrogen, progesterone and testosterone, are the major decisive factors of sex differences in mammals [33].…”

Host factors and vaccine efficacy: Implications for COVID‐19 vaccines

“…As well as microbiome produces antimicrobials and it plays a protective role by preventing pathogens from adhering to the intestinal membrane. 42 As about 70% of immune cells are located in the digestive system, the intestinal flora has a broad regulatory effect on the immune system. In other words, there is the active interplay between gut microbiota and immunity, the innate and adaptive immune response is influenced by the gut microbiota, which has an immunomodulatory effect.…”