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Gut bacterial translocation/dissemination explains the increased mortality produced by parenteral nutrition following
G P Zaloga1, P Roberts, K W Black
1Department of Anesthesia, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157-1009.
Abstract:
Mortality is reported to be higher in methotrexate (MTX)-treated animals receiving total parenteral nutrition (TPN), compared to animals receiving enteral nutrition. The increased mortality is felt to be related to gut atrophy and bacterial translocation. In this study, we examined the effect of MTX (30 mg/kg) on survival, body weight loss, gut mass, and gut bacterial translocation in rats randomized to TPN or enteral nutrition. Twenty-four male Sprague-Dawley rats (n = 8 per group) were randomized to TPN, a peptide-based enteral diet (PEP), or CHOW. Animals were weighed daily and followed for survival (6 days). A separate group of rats (n = 6 per group) were similarly randomized and sacrificed at 3 days. Mesenteric lymph node complex, liver, spleen, lung, and blood were cultured for translocating bacteria. Body weight loss was similar 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 CHOW (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 between TPN and CHOW. There were no significant differences between groups for gut weights or mucosal protein content. This study supports a direct relationship between bacterial translocation and mortality in rats following MTX.
Insights
Methotrexate (MTX) treatment increases mortality in rats receiving total parenteral nutrition (TPN), linked to bacterial translocation. Enteral nutrition mitigates this risk, suggesting gut health is crucial for survival during MTX therapy.
Area of Science:
- Gastroenterology
- Pharmacology
- Immunology
Background:
- Methotrexate (MTX) treatment is associated with increased mortality in animals receiving total parenteral nutrition (TPN).
- This heightened mortality is hypothesized to stem from gut atrophy and subsequent bacterial translocation.
Purpose of the Study:
- To investigate the impact of MTX on survival, body weight, gut mass, and bacterial translocation in rats under TPN versus enteral nutrition.
- To elucidate the relationship between MTX, nutritional support, and mortality via bacterial translocation.
Main Methods:
- Rats were randomized to receive MTX with TPN, a peptide-based enteral diet (PEP), or a standard chow diet (CHOW).
- Survival, body weight changes, and gut bacterial translocation to various organs (mesenteric lymph nodes, liver, spleen, lung, blood) were assessed over 6 days.
- Gut weights and mucosal protein content were measured in a separate cohort sacrificed at 3 days.
Main Results:
- Mortality was significantly higher in the TPN group (100%) compared to PEP (50%) and CHOW (25%) groups (P < 0.05).
- Bacterial translocation was extensive in TPN-fed rats, moderate in PEP-fed rats, and minimal in CHOW-fed rats.
- No significant differences in gut weights or mucosal protein content were observed across groups.
Conclusions:
- The study confirms a direct correlation between bacterial translocation and mortality in rats treated with MTX and receiving TPN.
- Enteral nutrition appears to reduce the risk of mortality associated with MTX by limiting bacterial translocation.