GUT BACTERIAL TRANSLOCATION DISSEMINATION EXPLAINS THE INCREASED MORTALITY PRODUCED BY PARENTERAL-NUTRITION FOLLOWING METHOTREXATE

Mortality is reported to be higher in methotrexate (MTX)-treated anima ls receiving total parenteral nutrition (TPN), compared to animals rec eiving enteral nutrition. The increased mortality is felt to be relate d to gut atrophy and bacterial translocation. In this study, we examin ed the effect of MTX (30 mg/kg) on survival, body weight loss, gut mas s, and gut bacterial translocation in rats randomized to TPN or entera l nutrition. Twenty-four male Sprague-Dawley rats (n = 8 per group) we re randomized to TPN, a peptide-based enteral diet (PEP), or CHOW. Ani mals were weighed daily and followed for survival (6 days). A separate group of rats (n = 6 per group) were similarly randomized and sacrifi ced at 3 days Mesenteric lymph node complex, liver. spleen, lung, and blood were cultured for translocating bacteria. Body weight loss was s imilar in all groups (12.0-16.9 g/day). Mortality was significantly (P < 0.05) higher in the TPN animals (100%), compared to PEP (50%) and C HOW (25%) fed animals. All tissues in the TPN animals contained large quantities of bacteria, while most tissues in the CHOW group were free of bacteria. Bacterial counts in the PEP tissues were intermediate be tween TPN and CHOW. There were no significant differences between grou ps for gut weights or mucosal protein content. This study supports a d irect relationship between bacterial translocation and mortality in ra ts following MTX.