Protective Effects and Associated Mechanisms of Cajá Juice (Spondias mombin L.) and Its Fermented Version with L. acidophilus NRRL B-4495 on 5-Fluorouracil-Induced Intestinal Mucositis in Mice
intestinal mucositis; Spondias mombin L.; L. acidophilus; fermentation; nutraceuticals; 5-FU.
Chemotherapy-induced intestinal mucositis (IM), particularly that caused by 5-fluorouracil (5 FU), represents a major therapeutic limitation and is characterized by epithelial damage, exacerbated inflammation, intestinal barrier dysfunction, and alterations in the gut microbiota. In this context, nutraceutical strategies based on foods rich in bioactive compounds and their combination with probiotics have emerged as promising alternatives. This study aimed to evaluate the effects of fresh cajá juice (Spondias mombin L.) and cajá juice fermented with Lactobacillus acidophilus in an experimental model of 5-FU-induced IM. Mice were allocated to experimental groups and orally administered the treatments for 18 days. Mucositis was induced on day 15 by an intraperitoneal injection of 5-FU. Histological parameters, inflammatory markers (IL-1β, IL-6, and TNF-α), mucin expression (MUC-2), intestinal enzyme activity (invertase), lactic acid bacteria counts before and after inflammation, and the fecal metabolic profile determined by gas chromatography were evaluated. The administration of 5 FU induced a 10.23% loss in body weight and increased intestinal histopathological damage. In the duodenum, jejunum, and ileum, the 5-FU group exhibited a median histopathological score of 3, whereas the saline group had a score of 0. Neither cajá juice treatment prevented body weight loss, with reductions of 14.91% in the fresh juice group and 14.57% in the fermented juice group. Nevertheless, both treatments reduced the median histopathological scores in the duodenum, jejunum, and ileum to 1 (p < 0.01 vs. the 5-FU group). Fermented cajá juice significantly preserved intestinal invertase activity (p < 0.05 vs. the 5-FU group). Both treatments also increased MUC-2 expression and reduced IL-1β and IL-6 concentrations (p < 0.05), as well as TNF-α levels (p < 0.001). On day 18, lactic acid bacteria counts were 7.2 ± 0.1 log CFU/g in the fresh juice group and 7.8 ± 0.6 log CFU/g in the fermented juice group, compared with 6.4 ± 0.2 log CFU/g in the saline group and 6.5 ± 0.1 log CFU/g in the 5-FU group (p < 0.05). Gas chromatography–mass spectrometry analysis identified the triterpenes α amyrone and α-amyrin exclusively in fecal samples from the treated groups. Overall, the findings demonstrate that cajá juice, particularly when fermented with L. acidophilus, attenuated histopathological damage and the inflammatory response, preserved structural and functional components of the intestinal mucosa, and modified the fecal bacterial and metabolic profiles, although it did not prevent 5-FU-induced body weight loss.