One of the leading global public-health burdens is metabolic syndrome (MetS), despite the many advances in pharmacotherapies. MetS, now known as “developmental origins of health and disease” (DOHaD), can have its origins in early life. Offspring MetS can be programmed by various adverse early-life conditions, such as nutrition imbalance, maternal conditions or diseases, maternal chemical exposure, and medication use. Conversely, early interventions have shown potential to revoke programming processes to prevent MetS of developmental origins, namely reprogramming. In this review, we summarize what is currently known about adverse environmental insults implicated in MetS of developmental origins, including the fundamental underlying mechanisms. We also describe animal models that have been developed to study the developmental programming of MetS. This review extends previous research reviews by addressing implementation of reprogramming strategies to prevent the programming of MetS. These mechanism-targeted strategies include antioxidants, melatonin, resveratrol, probiotics/prebiotics, and amino acids. Much work remains to be accomplished to determine the insults that could induce MetS, to identify the mechanisms behind MetS programming, and to develop potential reprogramming strategies for clinical translation.

Nano-sized extracellular vesicles (EV) are essential for cell communication. Studies on EV from natural sources including edible plants are gaining momentum due to the biological implications. In this study, EV from tomato fruit were isolated by ultracentrifugation and their physical and morphological features along with their biocargo profiles were analyzed. We found that tomato EV promote the growth of probiotic Lactobacillus species, while inhibiting growth of the opportunistic intestinal pathogens Clostridioides difficile and Fusobacterium nucleatum. Tomato EV reversed microbiota dysbiosis caused by F. nucleatum in a simulator of the gut microbiota fermentation model. Phospholipid analysis of tomato EV revealed that the anti-bacterial effect of tomato-EV was driven by the presence of specific lipids in the EV, as demonstrated by lipid depletion and reconstitution experiments. The findings suggest the potential of tomato-derived EV for treating gut microbiota dysbiosis and preventing intestinal bacterial infections.

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.

Resveratrol butyrate esters (RBE) are derivatives of resveratrol (RSV) and butyric acid and exhibit biological activity similar to that of RSV but with higher bioavailability. The aim of this study was designed as an animal experiment to explore the effects of RBE on the serum biochemistry, and fat deposits in the offspring rats exposed to bisphenol A (BPA), along with the growth and decline of gut microbiota. We constructed an animal model of perinatal Bisphenol A (BPA) exposure to observe the effects of RBE supplementation on obesity, blood lipids, and intestinal microbiota in female offspring rats. Perinatal exposure to BPA led to weight gain, lipid accumulation, high levels of blood lipids, and deterioration of intestinal microbiota in female offspring rats. RBE supplementation reduced the weight gain and lipid accumulation caused by BPA, optimised the levels of blood lipids, significantly reduced the Firmicutes/Bacteroidetes (F/B) ratio, and increased and decreased the abundance of S24-7 and Lactobacillus, respectively. The analysis of faecal short-chain fatty acid (SCFA) levels revealed that BPA exposure increased the faecal concentration of acetate, which could be reduced via RBE supplementation. However, the faecal concentrations of propionate and butyrate were not only significantly lower than that of acetate, but also did not significantly change in response to BPA exposure or RBE supplementation. Hence, RBE can suppress BPA-induced obesity in female offspring rats, and it demonstrates excellent modulatory activity on intestinal microbiota, with potential applications in perinatological research.