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Lactobacillus reuteri DSM 17938 and ATCC PTA 5289 ameliorates chemotherapy-induced oral mucositis

ABSTRACT: Oral mucositis (OM) is a common complication of cancer therapy, however OM management remains unsatisfactory. There is a growing interest in the therapeutic potential of probiotics in OM due to positive findings of its use in intestinal mucositis. This study aimed to determine the efficacy and safety of the probiotic combination Lactobacillus reuteri DSM 17938 and ATCC PTA 5289 strains in chemotherapy-induced OM. Mice were divided into 4 groups. PBS/water and PBS/LR groups comprised of mice injected with PBS intraperitoneally (i.p.), and were given water or the mixture of L. reuteri (LR) DSM 17938 and ATCC PTA 5289 in water respectively. The 5-FU/water and 5-FU/LR groups comprised of mice injected with 5-FU i.p., and were given water or L. reuteri DSM 17938 and ATCC PTA 5289 in water respectively. Histopathological analysis revealed that the oral epithelia of the 5-FU/water and 5-FU/LR groups were thinner compared to PBS/water and PBS/LR groups. However, epithelial damage was significantly reduced in the 5-FU/LR compared to 5-FU/water group. Additionally, the 5-FU/LR group showed reduced oxidative stress and inflammation in the oral mucosa. We further showed that L. reuteri reduced oxidative stress through the nuclear factor E2-related factor-2 (Nrf-2) signalling. There was no evidence of translocation of L. reuteri systemically. This study demonstrated for the first time that L. reuteri protected oral mucosa against damage induced by chemotherapy.

SUBMITTER: Gupta N

PROVIDER: S-EPMC7530769 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Project description:BackgroundLactobacillus spp. potentially contribute to health by modulating bacterial biofilm formation, but their effects on the overall oral microbiota remain unclear.Methods and findingsOral microbiota was characterized via 454-pyrosequencing of the 16S rDNA hypervariable region V3-V4 after 12 weeks of daily Lactobacillus reuteri DSM 17938 and PTA 5289 consumption. Forty-four adults were assigned to a test group (n = 22) that received lactobacilli lozenges (108 CFU of each strain/lozenge) or a control group that received placebo (n = 22). Presence of L. reuteri was confirmed by cultivation and species specific PCR. Tooth biofilm samples from 16 adults before, during, and after exposure were analyzed by pyrosequencing. A total of 1,310,292 sequences were quality filtered. After removing single reads, 257 species or phylotypes were identified at 98.5% identity in the Human Oral Microbiome Database. Firmicutes, Bacteroidetes, Fusobacteria, Proteobacteria, and Actinobacteria were the most abundant phyla. Streptococcus was the most common genus and the S. oralis/S. mitis/S. mitis bv2/S. infantis group comprised the dominant species. The number of observed species was unaffected by L. reuteri exposure. However, subjects who had consumed L. reuteri were clustered in a principal coordinates analysis relative to scattering at baseline, and multivariate modeling of pyrosequencing microbiota, and culture and PCR detected L. reuteri separated baseline from 12-week samples in test subjects. L. reuteri intake correlated with increased S. oralis/S. mitis/S. mitis bv2/S. infantis group and Campylobacter concisus, Granulicatella adiacens, Bergeyella sp. HOT322, Neisseria subflava, and SR1 [G-1] sp. HOT874 detection and reduced S. mutans, S. anginosus, N. mucosa, Fusobacterium periodicum, F. nucleatum ss vincentii, and Prevotella maculosa detection. This effect had disappeared 1 month after exposure was terminated.ConclusionsL. reuteri consumption did not affect species richness but induced a shift in the oral microbiota composition. The biological relevance of this remains to be elucidated.Trial registrationClinicalTrials.gov NCT02311218.

Project description:Following an application from BioGaia AB submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Sweden, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to orodispersible lozenges containing a combination of Lactobacillus reuteri DSM 17938 and Lactobacillus reuteri ATCC PTA 5289 and normal gum function. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The Panel considers that orodispersible lozenges containing L. reuteri DSM 17938 and L. reuteri ATCC PTA 5289 are sufficiently characterised. Maintenance of normal gum function is a beneficial physiological effect. Out of the two studies from which conclusions could be drawn and that investigated the effect of lozenges containing L. reuteri at the proposed conditions of use (i.e. consumption twice daily) on appropriate gingival outcomes (bleeding on probing (PoB) and gingival index (GI)) in subjects with gingivitis, but without periodontitis, one showed a large effect on BoP and other gingival outcomes and one showed no effect. No effect was found in one study with the use of one lozenge daily. The three studies that investigated, at the proposed conditions of use, modified GI (and not BoP or GI) in subjects with gingivitis, but without periodontitis, or were conducted in patients with periodontitis support an effect of lozenges with L. reuteri on gum function. Some evidence has been provided for mechanisms by which consumption of lozenges containing L. reuteri could improve outcomes of gingivitis in patients with chronic periodontitis but the relevance of such mechanisms for the target population of the claim (i.e. subjects without periodontitis) is unclear. The Panel concludes that the evidence provided is insufficient to establish a cause and effect relationship between the consumption of orodispersible lozenges containing a combination of L. reuteri DSM 17938 and L. reuteri ATCC PTA 5289 and maintenance of normal gum function.

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Lactobacillus reuteri DSM 17938 and ATCC PTA 5289 ameliorates chemotherapy-induced oral mucositis

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