Cardiovascular Diseases of Developmental Origins: Preventive Aspects of Gut Microbiota-Targeted Therapy

Abstract

Cardiovascular diseases (CVDs) can originate from early life. Accumulating evidence suggests that gut microbiota in early life is linked to CVDs in later life. Gut microbiota-targeted therapy has gained significant importance in recent decades for its health-promoting role in the prevention (rather than just treatment) of CVDs. Thus far, available gut microbiota-based treatment modalities used as reprogramming interventions include probiotics, prebiotics, and postbiotics. The purpose of this review is, first, to highlight current studies that link dysbiotic gut microbiota to the developmental origins of CVD. This is followed by a summary of the connections between the gut microbiota and CVD behind cardiovascular programming, such as short chain fatty acids (SCFAs) and their receptors, trimethylamine-N-oxide (TMAO), uremic toxins, and aryl hydrocarbon receptor (AhR), and the renin-angiotensin system (RAS). This review also presents an overview of how gut microbiota-targeted reprogramming interventions can prevent the developmental origins of CVD from animal studies. Overall, this review reveals that recent advances in gut microbiota-targeted therapy might provide the answers to reduce the global burden of CVDs. Still, additional studies will be needed to put research findings into practice.

Maternal 3,3-Dimethyl-1-Butanol Therapy Protects Adult Male Rat Offspring against Hypertension Programmed by Perinatal TCDD Exposure

“…In the current study, perinatal TCDD exposure causes the rise of offspring's BP coinciding with dysbiotic gut microbiota and impaired SCFAs production and receptor expression. In support of previous research indicating that gut microbiota dysbiosis contributes to hypertension [10,11,26], TCDD-induced hypertensive offspring displayed several microbial signatures such as reduced α-diversity, increased the F/B ratio, and a lesser abundance of beneficial microbes Ruminococcus, Roseburia, and Odoribacter [26,27]. On the other hand, maternal DMB therapy protects progeny against hypertension programmed by TCDD, which is related to alterations of gut microbiota composition, mediation of TMA-TMAO metabolic pathway, regulation of SCFA and their receptors, and restoration of the RAS and AHR signaling pathway.…”

“…Cumulative evidence suggests that gut microbiota and its metabolites contribute to the pathogenesis of hypertension [ 9 , 10 , 11 ]. Certain metabolites derived from gut microbes have been found to participate in the control of blood pressure (BP), such as trimethylamine N-oxide (TMAO) and short chain fatty acids (SCFAs) [ 12 , 13 ].…”

“…Since gut microbiota is highly relevant to hypertension, attention has been drawn to target on gut microbiota and related metabolites as new potential therapeutics to prevent hypertension of developmental origins [ 11 ]. Targeting TMA formation, 3,3-Dimethyl-1-butanol (DMB) can inhibit microbial choline TMA lyase activity to inhibit TMA and subsequent TMAO formation [ 16 ].…”

The First Thousand Days: Kidney Health and Beyond

“…Despite various early-life environmental factors related to CKD in later life, current evidence suggests that there may be common mechanisms behind renal programming. Although the complete mechanisms remain inconclusive, prior research has provided important information on certain molecular mechanisms, including oxidative stress [109], nitric oxide (NO) signaling [110], aberrant renin-angiotensin system (RAS) [111], and gut microbiota dysbiosis [112]. A summary of the integrated mechanisms of renal programming in response to various maternal insults for kidney disease of developmental origin is depicted in Figure 3.…”

“…Several adverse environmental factors in early life can shape the offspring's gut microbial composition, leading to consequent adverse offspring outcomes [125]. Conversely, maternal microbiota-targeted interventions have shown benefits against renal programming [112,126]. Importantly, several gut microbiota-derived uremic toxins are associated with cardiovascular disease (CVD) in CKD via the activation of the aryl hydrocarbon receptor (AHR) [127].…”