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Erhöhte Darmpermeabilität: Pathomechanismus für metabolische Erkrankungen?

Increased intestinal permeability: a pathomechanism for metabolic diseases?

  • Leitthema
  • Published:
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Zusammenfassung

Eine intakte Darmbarriere ist die Schnittstelle zwischen Umwelt‑, Verhaltens- und intrinsisch biologischen Faktoren und stellt einen wesentlichen Parameter der Integrität eines gesunden Organismus dar. Neben ihrer Rolle in einer Vielzahl physiologischer Prozesse kann die Darmmikrobiota zur Beeinträchtigung der Darmbarriere und Veränderung der intestinalen Permeabilität beitragen. Letztere wird sowohl über exogene Faktoren wie Ernährung, Alkohol, Medikamenteneinnahme und pathogene Bakterien als auch über körpereigene Mechanismen, die z. B. durch veränderte Immunabwehr oder gestörte Glukosetoleranz getriggert werden, reguliert. Aufgrund einer erhöhten Darmpermeabilität gelangen verstärkt Bakterien sowie deren Bestandteile in den Kreislauf, was systemisch zur Aggravation einer bestehenden Adipositas sowie einer zunehmenden Insulinresistenz bis hin zu kardiovaskulären Ereignissen beitragen kann. Außerdem kommt es auf der Ebene von Organen und Geweben durch die erhöhte bakterielle Exposition zu einem circulus vitiosus, in dem über eine Schädigung der lokalen Abwehr mit weiterer Erhöhung der Darmpermeabilität eine lokale inflammatorische Aktivierung entsteht, die einen systemischen proinflammatorischen, diabetogenen und atherogenen Status unterhält. Die Modulation der Darmpermeabilität durch Ernährung und andere Interventionen, einschließlich Manipulation des Darmmikrobioms durch Prä‑, Pro- oder Synbiotika, stellt ein potenzielles Präventions- und Behandlungsziel für kardiometabolische Erkrankungen dar, das aber derzeit in der klinischen Praxis noch kaum eine Rolle spielt. Voraussetzung für eine gezielte Therapie, die Veränderungen des Mikrobioms bewirken soll, ist ein besseres Verständnis der Wechselwirkungen zwischen Mikrobiota und kardiometabolischen Erkrankungen.

Abstract

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.

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  1. Medizinisches Department III – Endokrinologie, Nephrologie, Rheumatologie, Universitätsklinikum Leipzig, Liebigstr. 20, 04103, Leipzig, Deutschland

    Marie Patt, Lucas Massier, Peter Kovacs, Matthias Blüher &  Rima Chakaroun

  2. Karolinska Institutet, Department of medicine, Huddinge, Schweden

    Lucas Massier

  3. Helmholtz-Institut für Metabolismus‑, Adipositas- und Gefäßforschung (HI-MAG), Helmholtz Zentrum München an der Universität Leipzig und Universitätsklinik Leipzig, Leipzig, Deutschland

    Matthias Blüher

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M. Patt, L. Massier, P. Kovacs, M. Blüher und R. Chakaroun geben an, dass kein Interessenkonflikt besteht.

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Patt, M., Massier, L., Kovacs, P. et al. Erhöhte Darmpermeabilität: Pathomechanismus für metabolische Erkrankungen?. Diabetologe 17, 382–390 (2021). https://doi.org/10.1007/s11428-021-00726-y

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