Increased Intestinal Permeability: A Pathomechanism For Metabolic Diseases?

The intestinal barrier is an interface between ourselves and our environments and therefore an integral regulator of health. Among other factors, gut barrier integrity is regulated by bacteria and bacterial metabolites, which have been evidenced to have both protective or detrimental effects on gut integrity and permeability. Similarly, both external and internal factors related to host metabolic state can lead to alterations of tight junction integrity and hence to increased influx of bacteria or bacterial components into the host circulation. This so-called 'metabolic endotoxemia' has been associated with impaired metabolic host status, aggravation of existing obesity, increase in insulin resistance, and onset of cardiovascular events. From the gut, bacteria and their components and metabolites are further transported through the blood to peripheral tissues, where they can induce chronic pro-inflammatory signals at the tissue and systemic level. This, in turn, can further increase intestinal permeability leading to a detrimental feedback loop. Modulation of gut barrier function through nutritional or medicinal interventions, including manipulation of gut microbiota by pre-, pro- or synbiotics, represents a promising prevention and treatment target for metabolic diseases. Prerequisite for microbiome based targeted prevention and treatment options is a better understanding of the interactions between the microbiome and cardiovascular health.