Dietary manipulation of methotrexate-induced enterocolitis

Area of Science:

• Gastroenterology
• Oncology
• Nutritional Science

Background:

• Chemotherapy, such as methotrexate (MTX), causes severe enterocolitis, limiting its administration.
• Dietary interventions are crucial for mitigating chemotherapy-induced toxicity.
• Elemental diets (ED) and polypeptide diets (PPD) represent different nutritional approaches.

Purpose of the Study:

• To compare the effects of an elemental diet (ED) and a polypeptide diet (PPD) on morbidity and mortality following methotrexate (MTX) administration in rats.
• To evaluate the impact of glutamine supplementation in ED on MTX toxicity.
• To assess changes in intestinal bacteria and mucosal integrity.

Main Methods:

• Fischer 344 rats (n=80) were fed regular chow (RD), glycine-supplemented ED (Gly-ED), glutamine-supplemented ED (Glu-ED), or glycine-supplemented PPD (Gly-PPD) for 7 days prior to MTX administration.
• Animals were assessed for survival, and tissue/blood samples were collected for bacterial culture and mucosal analysis 72 hours post-MTX.

Main Results:

• The polypeptide diet (Gly-PPD) resulted in 100% survival, while the glutamine-supplemented elemental diet (Glu-ED) showed 25% survival.
• The elemental diet (ED) increased intestinal Gram-negative bacteria and decreased mucosal height and DNA/protein content.
• The polypeptide diet prevented mucosal atrophy and MTX-induced enterocolitis.

Conclusions:

• Polypeptide diets are superior to elemental diets in preventing MTX-induced enterocolitis and improving survival.
• Elemental diets exacerbate chemotherapy toxicity by altering gut microbiota and damaging the intestinal mucosa.
• Dietary composition plays a critical role in managing chemotherapy-related gastrointestinal side effects.