Short-chain fatty acids enhance intestinal adaptation in rats receiving total parenteral nutrition: A multi-organ analysis.

摘要

Following massive small bowel resection, the remnant intestine undergoes morphological and functional adaptive changes. Prior to these adaptive events, short bowel syndrome is characterized by diarrhea, weight loss, electrolyte abnormalities and multiple nutritional deficiencies. Accelerated skeletal muscle proteolysis and translocation of amino acids from skeletal muscle to visceral organs follows surgery. In addition, surgery has immunosuppressive effects by decreasing lymphocyte populations, granulocyte function, NK cell cytotoxicity and delayed hypersensitivity skin-test response. Current parenteral formulations do not provide nutrients specific to the gastrointestinal tract and result in gastrointestinal atrophy. To determine if SCFA supplementation of TPN influences the multiorgan response to surgery, male Sprague-Dawley rats underwent an 80% proximal jejunoileal resection and jugular catheterization. Animals were randomly assigned to receive standard total parenteral nutrition (TPN) or an isoenergetic, isonitrogenous TPN supplemented with SCFAs. SCFA-supplemented TPN reduced loss of skeletal muscle mass by 7 days following surgery which was further supported by decreased urinary 3-methylhistidine excretion, reduced epitrochlearis muscle protein degradation rate and higher plasma glutamine concentration. SCFAs enhanced various components of natural immunity following intestinal resection. SCFA-supplemented TPN prevented the abnormal hematological profiles exhibited in the standard TPN groups and enhanced the cytotoxic activity of natural killer cells. SCFA-supplemented TPN enhanced morphological and function adaptation of the remnant ileum. Abundance of proglucagon and ornithine decarboxylase mRNA were higher in the SCFA groups suggesting that these genes may be involved in SCFA-induced intestinal adaptation. To further examine mediators involved in the enterotrophic response to SCFAs, SCFA-supplemented TPN was infused for 6 to 72h in rats with normal, unresected small intestine. Jejunal mRNA abundance of the basolateral glucose transporter, GLUT2, was increased as early as 6 hours following SCFA-supplementation. Systemic administration of SCFAs resulted in the rapid upregulation of proliferative genes within the ileum such proglucagon, c-myc, c-jun, and c-fos. In conclusion, systemic administration of SCFAs benefits multiple organ systems following surgical trauma. The observation that enterotrophic genes are acutely upregulated following SCFA administration suggests a potential mechanism whereby SCFAs modulate intestinal adaptation. With this understanding, nutritionists will be able to devise new strategies to manipulate the intestine to maximize nutrient utilization.