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Anti-inflammatory effects of Lactococcus lactis NCDO 2118 during the remission period of chemically induced colitis.

Luerce TD, Gomes-Santos AC, Rocha CS, Moreira TG, Cruz DN, Lemos L, Sousa AL, Pereira VB, de Azevedo M, Moraes K, Cara DC, LeBlanc JG, Azevedo V, Faria AM, Miyoshi A - Gut Pathog (2014)

Bottom Line: Only one strain, L. lactis NCDO 2118, was able to reduce IL-1β-induced IL-8 secretion in Caco-2 cells, suggesting a potential anti-inflammatory effect.This protective effect was not attributable to changes in secretory IgA (sIgA); however, NCDO 2118 administration was associated with an early increase in IL-6 production and sustained IL-10 production in colonic tissue.Here, we identified a new probiotic strain with a potential role in the treatment of IBD, and we elucidated some of the mechanisms underlying its anti-inflammatory effect.

View Article: PubMed Central - HTML - PubMed

Affiliation: Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627 - 31270-901 Belo Horizonte, MG, Brazil.

ABSTRACT

Background: Many probiotic bacteria have been described as promising tools for the treatment and prevention of inflammatory bowel diseases (IBDs). Most of these bacteria are lactic acid bacteria, which are part of the healthy human microbiota. However, little is known about the effects of transient bacteria present in normal diets, including Lactococcus lactis.

Methods: In the present study, we analysed the immunomodulatory effects of three L. lactis strains in vitro using intestinal epithelial cells. L. lactis NCDO 2118 was administered for 4 days to C57BL/6 mice during the remission period of colitis induced by dextran sodium sulphate (DSS).

Results: Only one strain, L. lactis NCDO 2118, was able to reduce IL-1β-induced IL-8 secretion in Caco-2 cells, suggesting a potential anti-inflammatory effect. Oral treatment using L. lactis NCDO 2118 resulted in a milder form of recurrent colitis than that observed in control diseased mice. This protective effect was not attributable to changes in secretory IgA (sIgA); however, NCDO 2118 administration was associated with an early increase in IL-6 production and sustained IL-10 production in colonic tissue. Mice fed L. lactis NCDO 2118 had an increased number of regulatory CD4(+) T cells (Tregs) bearing surface TGF-β in its latent form (Latency-associated peptide-LAP) in the mesenteric lymph nodes and spleen.

Conclusions: Here, we identified a new probiotic strain with a potential role in the treatment of IBD, and we elucidated some of the mechanisms underlying its anti-inflammatory effect.

No MeSH data available.


Related in: MedlinePlus

Oral administration of L. lactis NCDO 2118 improved colon shortening and macroscopic score of colitis. (A) Experimental protocol. C57BL/6 mice received 2% DSS for 7 days. L. lactis NCDO 2118 was continually administered for 4 consecutive days during the remission period of colitis (arrows) between the first and second course of colitis. The control group received medium. Mice were sacrificed at days 14 and 21 (arrowheads). (B) Body weight from day 0 to day 21. (C) Colon length measured in cm. (D) Macroscopic score of colitis, including scores related to body weight, diarrhea and rectal bleeding. Bars are the mean of 6 mice/group, and the data are representative of three independent experiments; ANOVA, Tukey post-test. *, p < 0.05, **, p < 0.01, ***, p < 0.001.
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Figure 2: Oral administration of L. lactis NCDO 2118 improved colon shortening and macroscopic score of colitis. (A) Experimental protocol. C57BL/6 mice received 2% DSS for 7 days. L. lactis NCDO 2118 was continually administered for 4 consecutive days during the remission period of colitis (arrows) between the first and second course of colitis. The control group received medium. Mice were sacrificed at days 14 and 21 (arrowheads). (B) Body weight from day 0 to day 21. (C) Colon length measured in cm. (D) Macroscopic score of colitis, including scores related to body weight, diarrhea and rectal bleeding. Bars are the mean of 6 mice/group, and the data are representative of three independent experiments; ANOVA, Tukey post-test. *, p < 0.05, **, p < 0.01, ***, p < 0.001.

Mentions: Based on our in vitro results, L. lactis NCDO 2118 was then selected for testing in vivo. The effect of oral administration of this strain was tested in a murine model of chemically induced colitis during the remission period and after a second colitis cycle. This experimental protocol mimics the remission and active periods of IBD. As shown in Figure 2B, the body weight of mice significantly decreased during DSS treatment compared to the body weight of water-treated mice (control group). After DSS withdrawal, the mice gradually recovered their body weight in all experimental groups. Treatment with L. lactis NCDO 2118 did not contribute to a significant change in weight gain (Figure 2B). A reduction in colon length at day 14 in the DSS and DSS + NCDO2118 groups was also observed (Figure 2C). Nevertheless, at the end of the experiment on day 21, oral treatment with L. lactis led to the restoration of colon length (Figure 2C). Mice consuming L. lactis exhibited significantly reduced clinical symptoms (macroscopic inflammatory score) in the recovery phase and upon colitis induction (Figure 2D), despite the severity of inflammation after the second colitis cycle. These findings suggest that L. lactis NCDO2118 administered in vivo has an anti-inflammatory effect.


Anti-inflammatory effects of Lactococcus lactis NCDO 2118 during the remission period of chemically induced colitis.

Luerce TD, Gomes-Santos AC, Rocha CS, Moreira TG, Cruz DN, Lemos L, Sousa AL, Pereira VB, de Azevedo M, Moraes K, Cara DC, LeBlanc JG, Azevedo V, Faria AM, Miyoshi A - Gut Pathog (2014)

Oral administration of L. lactis NCDO 2118 improved colon shortening and macroscopic score of colitis. (A) Experimental protocol. C57BL/6 mice received 2% DSS for 7 days. L. lactis NCDO 2118 was continually administered for 4 consecutive days during the remission period of colitis (arrows) between the first and second course of colitis. The control group received medium. Mice were sacrificed at days 14 and 21 (arrowheads). (B) Body weight from day 0 to day 21. (C) Colon length measured in cm. (D) Macroscopic score of colitis, including scores related to body weight, diarrhea and rectal bleeding. Bars are the mean of 6 mice/group, and the data are representative of three independent experiments; ANOVA, Tukey post-test. *, p < 0.05, **, p < 0.01, ***, p < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4126083&req=5

Figure 2: Oral administration of L. lactis NCDO 2118 improved colon shortening and macroscopic score of colitis. (A) Experimental protocol. C57BL/6 mice received 2% DSS for 7 days. L. lactis NCDO 2118 was continually administered for 4 consecutive days during the remission period of colitis (arrows) between the first and second course of colitis. The control group received medium. Mice were sacrificed at days 14 and 21 (arrowheads). (B) Body weight from day 0 to day 21. (C) Colon length measured in cm. (D) Macroscopic score of colitis, including scores related to body weight, diarrhea and rectal bleeding. Bars are the mean of 6 mice/group, and the data are representative of three independent experiments; ANOVA, Tukey post-test. *, p < 0.05, **, p < 0.01, ***, p < 0.001.
Mentions: Based on our in vitro results, L. lactis NCDO 2118 was then selected for testing in vivo. The effect of oral administration of this strain was tested in a murine model of chemically induced colitis during the remission period and after a second colitis cycle. This experimental protocol mimics the remission and active periods of IBD. As shown in Figure 2B, the body weight of mice significantly decreased during DSS treatment compared to the body weight of water-treated mice (control group). After DSS withdrawal, the mice gradually recovered their body weight in all experimental groups. Treatment with L. lactis NCDO 2118 did not contribute to a significant change in weight gain (Figure 2B). A reduction in colon length at day 14 in the DSS and DSS + NCDO2118 groups was also observed (Figure 2C). Nevertheless, at the end of the experiment on day 21, oral treatment with L. lactis led to the restoration of colon length (Figure 2C). Mice consuming L. lactis exhibited significantly reduced clinical symptoms (macroscopic inflammatory score) in the recovery phase and upon colitis induction (Figure 2D), despite the severity of inflammation after the second colitis cycle. These findings suggest that L. lactis NCDO2118 administered in vivo has an anti-inflammatory effect.

Bottom Line: Only one strain, L. lactis NCDO 2118, was able to reduce IL-1β-induced IL-8 secretion in Caco-2 cells, suggesting a potential anti-inflammatory effect.This protective effect was not attributable to changes in secretory IgA (sIgA); however, NCDO 2118 administration was associated with an early increase in IL-6 production and sustained IL-10 production in colonic tissue.Here, we identified a new probiotic strain with a potential role in the treatment of IBD, and we elucidated some of the mechanisms underlying its anti-inflammatory effect.

View Article: PubMed Central - HTML - PubMed

Affiliation: Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627 - 31270-901 Belo Horizonte, MG, Brazil.

ABSTRACT

Background: Many probiotic bacteria have been described as promising tools for the treatment and prevention of inflammatory bowel diseases (IBDs). Most of these bacteria are lactic acid bacteria, which are part of the healthy human microbiota. However, little is known about the effects of transient bacteria present in normal diets, including Lactococcus lactis.

Methods: In the present study, we analysed the immunomodulatory effects of three L. lactis strains in vitro using intestinal epithelial cells. L. lactis NCDO 2118 was administered for 4 days to C57BL/6 mice during the remission period of colitis induced by dextran sodium sulphate (DSS).

Results: Only one strain, L. lactis NCDO 2118, was able to reduce IL-1β-induced IL-8 secretion in Caco-2 cells, suggesting a potential anti-inflammatory effect. Oral treatment using L. lactis NCDO 2118 resulted in a milder form of recurrent colitis than that observed in control diseased mice. This protective effect was not attributable to changes in secretory IgA (sIgA); however, NCDO 2118 administration was associated with an early increase in IL-6 production and sustained IL-10 production in colonic tissue. Mice fed L. lactis NCDO 2118 had an increased number of regulatory CD4(+) T cells (Tregs) bearing surface TGF-β in its latent form (Latency-associated peptide-LAP) in the mesenteric lymph nodes and spleen.

Conclusions: Here, we identified a new probiotic strain with a potential role in the treatment of IBD, and we elucidated some of the mechanisms underlying its anti-inflammatory effect.

No MeSH data available.


Related in: MedlinePlus