• Tim Lubbers, Jacco J de Haan, Misha D P Luyer, Isabelle Verbaeys, M'hamed Hadfoune, Cornelis H C Dejong, Wim A Buurman, and Jan Willem M Greve.
• Department of Surgery, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands.
• Ann. Surg. 2010 Aug 1;252(2):376-82.

ObjectiveThe current study investigates activation of the nutritional anti-inflammatory pathway by lipid-rich nutrition.BackgroundEnteral nutrition activates humoral and neural pathways to regulate food intake and sustain energy balance. Recently, we demonstrated that enteral nutrition and in particular lipid-rich nutrition modulates inflammation and prevents organ damage.MethodsMale rats were fasted or fed lipid-rich nutrition before hemorrhagic shock. Disruption of afferent vagal fibers with capsaicin (deafferentation) was used to investigate involvement of afferent fibers. Peripheral activation of afferent vagal fibers via cholecystokinin (CCK)-mediated activation of CCK-1 receptors was investigated using administration of the selectively peripheral acting CCK-1 receptor antagonist, A70104 and PEGylated-CCK9. Tissue and blood were collected 90 minutes after shock to assess systemic inflammation and intestinal integrity.ResultsDeafferentation reversed the inhibitory effect of lipid-rich nutrition on systemic levels of tumor necrosis factor-alpha and interleukin-6, and on intestinal leakage of horseradish peroxidase and bacterial translocation. Furthermore, the protective effects of lipid-rich nutrition were negated by A70104, indicating that lipid-rich nutrition triggers peripheral CCK-1 receptors on vagal afferents to modulate inflammation. These findings were substantiated by the fact that pretreatment of fasted rats with PEGylated-CCK9, which acts on peripheral CCK-1 receptors, attenuated systemic inflammation, and loss of intestinal integrity.ConclusionThese data demonstrate that enteral lipid-rich nutrition modulates inflammation and preserves intestinal integrity via CCK release which activates CCK-1 receptors located on afferent vagal fibers. Taken together, the current study reveals a novel gut-brain-immune axis and provides new insight into the applicability of enteral nutrition to treat inflammatory conditions.

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