Leaky gut syndrome is a medical condition characterized by intestinal hyperpermeability. Since the intestinal barrier is one of the essential components maintaining homeostasis along the gastrointestinal tract, loss of its integrity due to changes in bacterial composition, decreased expression levels of tight junction proteins, and increased concentration of pro-inflammatory cytokines may lead to intestinal hyperpermeability followed by the development of gastrointestinal and non-gastrointestinal diseases. Translocation of microorganisms and their toxic metabolites beyond the gastrointestinal tract is one of the fallouts of the leaky gut syndrome. The presence of intestinal bacteria in sterile tissues and distant organs may cause damage due to chronic inflammation and progression of disorders, including inflammatory bowel diseases, liver cirrhosis, and acute pancreatitis. Currently, there are no medical guidelines for the treatment or prevention of bacterial translocation in patients with the leaky gut syndrome; however, several studies suggest that dietary intervention can improve barrier function and restrict bacteria invasion. This review contains current literature data concerning the influence of diet, dietary supplements, probiotics, and drugs on intestinal permeability and bacterial translocation.

This review summarizes the recent knowledge on the effects of dietary carbohydrates and lipids on the pathophysiology of leaky gut syndrome (LGS). Alterations in intestinal barrier permeability may lead to serious gastrointestinal (GI) disorders. LGS is caused by intestinal hyperpermeability due to changes in the expression levels and functioning of tight junctions. The influence of dietary habits on intestinal physiology is clearly visible in incidence rates of intestinal diseases in industrial and developing countries. Diseases which are linked to intestinal hyperpermeability tend to localize to Westernized countries, where a diet rich in fats and refined carbohydrates predominates. Several studies suggest that fructose is one of the key carbohydrates involved in the regulation of the intestinal permeability and its overuse may cause harmful effects, such as tight junction protein dysfunction. On the other hand, short chain fatty acids (mainly butyrate) at appropriate concentrations may lead to the reduction of intestinal permeability, which is beneficial in LGS. However, long chain fatty acids, including n-3 and n-6 polyunsaturated fatty acids have unclear properties. Some of those behave as components untightening and tightening the intestinal membrane.

Enkefalinazy, należące do rodziny metaloproteaz zależnych od jonów cynku pełnią ważną rolę w regulacji aktywności endogennego układu opioidowego (ang. endogenous opioid system, EOS). Inhibitory enkefalinaz pozwalają na zwiększenie stężenia wybranych endogennych peptydów opioidowych, co znalazło zastosowanie w lecznictwie. Pierwszym lekiem opartym na tym mechanizmie działania był racekadotryl, wykazujący działanie przeciwbiegunkowe. W przeciwieństwie do innych leków wpływających na aktywność EOS, stosowanie racekadotrylu wiąże się z niższym prawdopodobieństwem wystąpienia efektów ubocznych, co może być kluczowym kryterium przy doborze leczenia u pacjentów z przewlekłymi chorobami jelit, którym towarzyszy biegunka. Dominujący udział EOS w modulacji informacji nocyceptywnej stwarza również perspektywy do zastosowania inhibitorów enkefalinaz w leczeniu bólu. W pracy omówiono zastosowanie inhibitorów enkefalinaz w chorobach układu pokarmowego, takich jak zespół jelita drażliwego oraz nieswoiste choroby zapalne jelit.