Biomolecular Actions by Intestinal Endotoxemia in Metabolic Syndrome

Ioannis Alexandros Charitos, Maria Aliani, Pasquale Tondo, Maria Venneri, Giorgio Castellana, Giulia Scioscia, Francesca Castellaneta, Donato Lacedonia, Mauro Carone

International Journal of Molecular Sciences · 2024 · 18 citations · 93 references

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TL;DR

Metabolic syndrome comprises interrelated metabolic disorders—visceral adiposity, dyslipidemia, hypertension, insulin resistance, and inflammation—that drive systemic diseases, and recent metabolomic studies highlight the intestinal microbiota’s dysbiosis and toxic metabolites as key contributors. This study seeks to describe current knowledge of the intestinal microbiota and its metabolome, and to analyze how their dysbiosis and endotoxemia interact with metabolic disease pathophysiology, with the goal of informing interventions that could slow or prevent metabolic syndrome. The authors examine the relationships between intestinal microbiota functions and the local and systemic metabolome, focusing on endotoxemia, to elucidate how dysbiosis contributes to metabolic disease.

Abstract

Metabolic syndrome (MetS) is a combination of metabolic disorders that concurrently act as factors promoting systemic pathologies such as atherosclerosis or diabetes mellitus. It is now believed to encompass six main interacting conditions: visceral fat, imbalance of lipids (dyslipidemia), hypertension, insulin resistance (with or without impairing both glucose tolerance and fasting blood sugar), and inflammation. In the last 10 years, there has been a progressive interest through scientific research investigations conducted in the field of metabolomics, confirming a trend to evaluate the role of the metabolome, particularly the intestinal one. The intestinal microbiota (IM) is crucial due to the diversity of microorganisms and their abundance. Consequently, IM dysbiosis and its derivate toxic metabolites have been correlated with MetS. By intervening in these two factors (dysbiosis and consequently the metabolome), we can potentially prevent or slow down the clinical effects of the MetS process. This, in turn, may mitigate dysregulations of intestinal microbiota axes, such as the lung axis, thereby potentially alleviating the negative impact on respiratory pathology, such as the chronic obstructive pulmonary disease. However, the biomolecular mechanisms through which the IM influences the host’s metabolism via a dysbiosis metabolome in both normal and pathological conditions are still unclear. In this study, we seek to provide a description of the knowledge to date of the IM and its metabolome and the factors that influence it. Furthermore, we analyze the interactions between the functions of the IM and the pathophysiology of major metabolic diseases via local and systemic metabolome’s relate endotoxemia.

References

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