Mitigation of chemotherapy-induced experimental intestinal mucositis through postbiotic lactate

Lett Appl Microbiol. 2024 Nov 6;77(11):ovae103. doi: 10.1093/lambio/ovae103.

Abstract

Postbiotic lactate modulates the immune system in inflammatory bowel diseases. However, its role in experimental intestinal mucositis (IM) has not been elucidated. This study aimed to evaluate the effects of lactate supplementation (1 and 2 × 10-1 mol/l) in a 5-fluorouracil (5-FU)-induced IM model. Male BALB/c mice (6-8 weeks old) were randomly divided into four groups: control (CTL), mucositis (MUC), mucositis with 1 × 10-1 mol/l lactate solution (MUC10), and mucositis with 2 × 10-1 mol/l lactate solution (MUC200). Lactate was administered via oral gavage for 10 days. Following the treatment period, the animals were subjected to an intraperitoneal injection of 300 mg/kg 5-FU to induce IM and were euthanized 72 h later for analysis. The MUC group presented intestinal damage with a poor histological score and decreased morphometric parameters as well as decreased mucus production and increased inflammatory infiltration and intestinal permeability compared to those of the CTL group (P < .05). However, the MUC200 group exhibited better results for the evaluated parameters than the MUC group (P < .05). Notably, the results in the MUC10 group were similar to those in the MUC group (P > .05). In conclusion, lactate supplementation attenuates mucositis-induced damage in a dose-dependent manner.

Keywords: 5-fluorouracil; lactate; mucositis; postbiotic.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Fluorouracil* / adverse effects
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / pathology
  • Lactic Acid* / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C*
  • Mucositis* / chemically induced
  • Mucositis* / drug therapy
  • Mucositis* / pathology
  • Mucositis* / prevention & control

Substances

  • Lactic Acid
  • Fluorouracil