Folate-producing lactic acid bacteria reduce inflammation in mice with induced intestinal mucositis

J Appl Microbiol. 2018 Nov;125(5):1494-1501. doi: 10.1111/jam.14038. Epub 2018 Aug 19.

Abstract

Aim: To evaluate two folate-producing strains, Streptococcus (Strep.) thermophilus CRL 808 and Strep. thermophilus CRL 415, against chemically induced mucositis in mice.

Methods and results: In vitro assays with Caco-2 cells were performed to evaluate the effect of the bacteria in the presence of 5-fluorouracil (5-FU). For in vivo studies, mice were daily injected with 5-FU to induce intestinal mucositis (IM) and orally administered with folate-producing strains during 6 days. Clinical symptoms, histological parameters and cytokine profiles were assessed. The results showed that Strep. thermophilus CRL 808 increased the cytotoxicity of 5-FU against Caco-2 cells. Administration of this strain in mice with chemically induced IM resulted in a reduction in diarrhoea score and restoration of the intestinal architecture. Cytokine analysis showed that the anti-inflammatory effect by the bacterium is not associated with an immune mechanism. Regarding Strep. thermophilus CRL 415, no improvements were observed in any of the parameters evaluated.

Conclusion: The administration of the folate-producing Strep. thermophilus CRL 808 has the potential to prevent IM induced by 5-FU in mice.

Significance and impact of the study: Folate-producing LAB could be used in chemotherapy patients to reduce the symptoms of IM, improve their nutritional status and increase the effectiveness of 5-FU.

Keywords: 5-fluorouracil; chemotherapy; folate; inflammation; lactic acid bacteria; mucositis; probiotic.

MeSH terms

  • Animals
  • Caco-2 Cells
  • Cytokines / metabolism
  • Diarrhea / prevention & control
  • Fluorouracil
  • Folic Acid / biosynthesis*
  • Humans
  • Inflammation / pathology
  • Intestinal Mucosa / pathology
  • Intestines / pathology
  • Lactobacillales / genetics
  • Lactobacillales / metabolism*
  • Mice
  • Mucositis / chemically induced
  • Mucositis / therapy*
  • Probiotics / therapeutic use*
  • Streptococcus thermophilus / genetics
  • Streptococcus thermophilus / metabolism

Substances

  • Cytokines
  • Folic Acid
  • Fluorouracil