The human body is exposed to many xenobiotic, potentially harmful compounds. The intestinal immune system is crucial in protecting the human body from these substances. Moreover, many microorganisms, residing in the gastrointestinal tract, play an important role in modulating immune responses. Pre- and probiotics may have beneficial effects on the microbial composition and activity within the human gut, subsequently affecting the immune system. Prebiotics can exert their effects via different mechanisms, like selectively stimulating the growth of bacteria by providing substrates or via direct immune stimulation. Probiotics may have beneficial health effects via competition with pathogens for substrates and binding intestinal sites, bioconversions of for example sugars into fermentation products with inhibitory properties, production of growth substrates like vitamins for the host, direct antagonism of pathogens via antimicrobial peptide production, reduction of inflammation and stimulation of immune cells. This review focuses on the different mechanisms via which the pre- and probiotics exert their beneficial effects on the host, addressing their immunomodulatory properties in particular.
Myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide. Improved survival has led to an increasing incidence of ischemic cardiomyopathy, making it a major reason for hospitalization in the western world. The inflammatory response in the ischemic myocardium determines the extent of structural remodeling and functional deterioration, with neutrophils (PMN) being a key modulator of the propagation and resolution of inflammation. The heme enzyme myeloperoxidase (MPO) is abundantly expressed in PMN and is an important mediator of their inflammatory capacities. Here, we examine the effects of PMN reduction, MPO deficiency and MPO inhibition in two murine models of MI. Reduction in PMN count resulted in less scar formation and improved cardiac function. Similar results were obtained in genetically MPO deficient mice, suggesting that MPO is a critical factor in PMN-mediated cardiac remodeling. To test our findings in a therapeutic approach, we orally administered the MPO inhibitor AZM198 in the context of MI and could demonstrate improved cardiac function and reduced structural remodeling. Therefore, MPO appears to be a favorable pharmacological target for the prevention of long-term morbidity after MI.
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