Cancer cachexia is characterized by systemic inflammation and severe metabolic imbalance, which may compromise the cellular components of the enteric nervous system (ENS). Oxidative stress associated with tumor growth can contribute to enteric neuropathy and gastrointestinal dysfunction.

This study investigated the effects of dietary L-glutamine supplementation on enteric neurons, glial cells, serotonergic cells, and jejunal wall morphology in Walker-256 tumor-bearing rats. Forty-eight male Wistar rats were distributed into four groups: control (C), control supplemented with 2% L-glutamine (G), Walker-256 tumor (T), and tumor supplemented with 2% L-glutamine (TG).

After a 14-day experimental period, jejunal samples were collected for immunohistochemistry, morphometric analysis, and Western blotting of GFAP, S100, and GDNF proteins. Tumor-bearing rats showed marked reductions in neuronal and glial densities, decreased numbers of serotonergic cells, and significant thinning of the jejunal wall.

L-glutamine supplementation preserved neuronal and glial populations in tumor-bearing animals, increased GFAP-associated glial network organization, and restored serotonergic cell density and intestinal wall thickness. In contrast, supplementation in healthy animals was associated with reductions in neuronal and glial densities.

These findings indicate that L-glutamine supplementation exerts neuroprotective and gliotrophic effects on the ENS under tumor-induced cachexia, possibly through mechanisms related to oxidative stress modulation. However, its effects in healthy conditions appear to differ and require further investigation.