Lactobacillus fermentum BR11 and Fructo-Oligosaccharide Partially Reduce Jejunal Inflammation in a Model of Intestinal Mucositis in Rats

Abstract

Although probiotics are beginning to enter mainstream medicine for disorders of the colon, their effects on the small bowel remain largely unexplored. We investigated the recently identified probiotic, Lactobacillus fermentum (L. fermentum) BR11 (BR11) and the prebiotic, fructo-oligosaccharide (FOS), both individually and in synbiotic combination, for their potential to alleviate intestinal mucositis. From Days 0–9, rats consumed skim milk (SM; saline + SM), low dose (LD-BR11; 1 × 10 ⁶ cfu/ml), high dose (HD-BR11; 1 × 10 ⁹ cfu/ml), LD-FOS (3%), HD-FOS (6%), or synbiotic (HD-BR11/FOS). On Day 7, rats were injected with 5-fluorouracil (5-FU; 150 mg/kg). All rats were sacrificed on Day 10. Intestinal tissues were collected for quantitative histology, sucrase, and myeloperoxidase (MPO) determinations. 5-FU decreased sucrase activity, villus height, crypt depth, and crypt cell proliferation compared to controls. Compared to 5-FU + SM, histological damage severity scores were increased for all treatments, although all were effective at reducing jejunal inflammation, indicated by reduced MPO activity ( P < 0.05). The combination of BR11 and FOS did not provide additional protection. Moreover, HD-FOS and the synbiotic actually increased clinical mucositis severity ( P < 0.05). We conclude that L. fermentum BR11 has the potential to reduce inflammation of the upper small intestine. However, its combination with FOS does not appear to confer any further therapeutic benefit for the alleviation of mucositis.

ACKNOWLEDGMENTS

The authors would like to acknowledge Kerry Lymn and Katie Tooley for their assistance throughout the animal trial and Betty Zacharakis and Esther Staunton for IRMS analysis of breath samples. The authors would also like to thank Dr. Philip Giffard and Dr. Mark Turner (Infectious Diseases Program, School of Life Sciences, Queensland University of Technology, Queensland) for providing L. fermentum BR11. Associate Professor Gordon Howarth is supported by a Cancer Council South Australia Research Fellowship.

Notes

^§ indicates P < 0.05 compared to saline + SM. ∗ indicates P < 0.05 compared to 5-FU + SM.

β indicates P < 0.05 compared to 5-FU + synbiotic. indicates P < 0.05 compared to 5-FU + HD-FOS. χ indicates P < 0.05 compared to 5-FU + LD-BR11.