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Lactobacillus johnsonii N6.2 mitigates the development of type 1 diabetes in BB-DP rats.

Valladares R, Sankar D, Li N, Williams E, Lai KK, Abdelgeliel AS, Gonzalez CF, Wasserfall CH, Larkin J, Schatz D, Atkinson MA, Triplett EW, Neu J, Lorca GL - PLoS ONE (2010)

Bottom Line: A decreased oxidative intestinal environment was evidenced by decreased expression of several oxidative response proteins in the intestinal mucosa (Gpx1, GR, Cat).The administration of L. johnsonii also resulted in higher levels of the tight junction protein claudin.These data also support therapeutic efforts that seek to modify gut microbiota as a means to modulate development of this disorder.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Cell Science, University of Florida, Gainesville, Florida, United States of America.

ABSTRACT

Background: The intestinal epithelium is a barrier that composes one of the most immunologically active surfaces of the body due to constant exposure to microorganisms as well as an infinite diversity of food antigens. Disruption of intestinal barrier function and aberrant mucosal immune activation have been implicated in a variety of diseases within and outside of the gastrointestinal tract. With this model in mind, recent studies have shown a link between diet, composition of intestinal microbiota, and type 1 diabetes pathogenesis. In the BioBreeding rat model of type 1 diabetes, comparison of the intestinal microbial composition of diabetes prone and diabetes resistant animals found Lactobacillus species were negatively correlated with type 1 diabetes development. Two species, Lactobacillus johnsonii and L. reuteri, were isolated from diabetes resistant rats. In this study diabetes prone rats were administered pure cultures of L. johnsonii or L. reuteri isolated from diabetes resistant rats to determine the effect on type 1 diabetes development.

Methodology/principal: Findings Results Rats administered L. johnsonii, but not L. reuteri, post-weaning developed type 1 diabetes at a protracted rate. Analysis of the intestinal ileum showed administration of L. johnsonii induced changes in the native microbiota, host mucosal proteins, and host oxidative stress response. A decreased oxidative intestinal environment was evidenced by decreased expression of several oxidative response proteins in the intestinal mucosa (Gpx1, GR, Cat). In L. johnsonii fed animals low levels of the pro-inflammatory cytokine IFNgamma were correlated with low levels of iNOS and high levels of Cox2. The administration of L. johnsonii also resulted in higher levels of the tight junction protein claudin.

Conclusions: It was determined that the administration of L. johnsonii isolated from BioBreeding diabetes resistant rats delays or inhibits the onset of type 1 diabetes in BioBreeding diabetes prone rats. Taken collectively, these data suggest that the gut and the gut microbiota are potential agents of influence in type 1 diabetes development. These data also support therapeutic efforts that seek to modify gut microbiota as a means to modulate development of this disorder.

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Related in: MedlinePlus

mRNA levels of the pro-inflammatory cytokine genes, IFNγ and TNFα linked to the oxidative stress response in the host.Relative expression was calculated as previously described relative to the value in the L. johnsonii feed group (expression  = 1). Relative expression in the L. johnsonii feed group (black bars), healthy control (dark grey bars), and diabetic animals (grey bars). The values are means +S.D. (N = 6); *P<0.05; #P<0.01.
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pone-0010507-g006: mRNA levels of the pro-inflammatory cytokine genes, IFNγ and TNFα linked to the oxidative stress response in the host.Relative expression was calculated as previously described relative to the value in the L. johnsonii feed group (expression  = 1). Relative expression in the L. johnsonii feed group (black bars), healthy control (dark grey bars), and diabetic animals (grey bars). The values are means +S.D. (N = 6); *P<0.05; #P<0.01.

Mentions: IFNγ is an important mediator of inflammatory responses with pleiotropic effects in the host. It was previously reported that IFNγ induces the expression of iNOS [14] while repressing the expression of Cox2 [15]. The aim was to determine if a negative correlation existed between the levels of pro-inflammatory cytokines, particularly IFNγ and TNFα, and the L. johnsonii-mediated decrease in oxidative stress response in the host. The mRNA levels of TNFα decreased ∼7 fold (P<0.05) between the healthy and diabetic animals, but no differences between the healthy control group and L. johnsonii fed group were observed (Fig. 6). The results indicate that the low expression of TNFα is correlated with healthy status and not with the administration of bacteria. The expression of IFNγ, on the contrary, was directly linked to the administration of L. johnsonii. Diabetic animals exhibited a ∼20 fold higher expression (P<0.005) of IFNγ compared to the L. johnsonii fed group. No significant differences were observed between the healthy controls and diabetic animals indicating a specific contribution of the probiotic microorganism to the decrement of the inflammatory response.


Lactobacillus johnsonii N6.2 mitigates the development of type 1 diabetes in BB-DP rats.

Valladares R, Sankar D, Li N, Williams E, Lai KK, Abdelgeliel AS, Gonzalez CF, Wasserfall CH, Larkin J, Schatz D, Atkinson MA, Triplett EW, Neu J, Lorca GL - PLoS ONE (2010)

mRNA levels of the pro-inflammatory cytokine genes, IFNγ and TNFα linked to the oxidative stress response in the host.Relative expression was calculated as previously described relative to the value in the L. johnsonii feed group (expression  = 1). Relative expression in the L. johnsonii feed group (black bars), healthy control (dark grey bars), and diabetic animals (grey bars). The values are means +S.D. (N = 6); *P<0.05; #P<0.01.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2865539&req=5

pone-0010507-g006: mRNA levels of the pro-inflammatory cytokine genes, IFNγ and TNFα linked to the oxidative stress response in the host.Relative expression was calculated as previously described relative to the value in the L. johnsonii feed group (expression  = 1). Relative expression in the L. johnsonii feed group (black bars), healthy control (dark grey bars), and diabetic animals (grey bars). The values are means +S.D. (N = 6); *P<0.05; #P<0.01.
Mentions: IFNγ is an important mediator of inflammatory responses with pleiotropic effects in the host. It was previously reported that IFNγ induces the expression of iNOS [14] while repressing the expression of Cox2 [15]. The aim was to determine if a negative correlation existed between the levels of pro-inflammatory cytokines, particularly IFNγ and TNFα, and the L. johnsonii-mediated decrease in oxidative stress response in the host. The mRNA levels of TNFα decreased ∼7 fold (P<0.05) between the healthy and diabetic animals, but no differences between the healthy control group and L. johnsonii fed group were observed (Fig. 6). The results indicate that the low expression of TNFα is correlated with healthy status and not with the administration of bacteria. The expression of IFNγ, on the contrary, was directly linked to the administration of L. johnsonii. Diabetic animals exhibited a ∼20 fold higher expression (P<0.005) of IFNγ compared to the L. johnsonii fed group. No significant differences were observed between the healthy controls and diabetic animals indicating a specific contribution of the probiotic microorganism to the decrement of the inflammatory response.

Bottom Line: A decreased oxidative intestinal environment was evidenced by decreased expression of several oxidative response proteins in the intestinal mucosa (Gpx1, GR, Cat).The administration of L. johnsonii also resulted in higher levels of the tight junction protein claudin.These data also support therapeutic efforts that seek to modify gut microbiota as a means to modulate development of this disorder.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Cell Science, University of Florida, Gainesville, Florida, United States of America.

ABSTRACT

Background: The intestinal epithelium is a barrier that composes one of the most immunologically active surfaces of the body due to constant exposure to microorganisms as well as an infinite diversity of food antigens. Disruption of intestinal barrier function and aberrant mucosal immune activation have been implicated in a variety of diseases within and outside of the gastrointestinal tract. With this model in mind, recent studies have shown a link between diet, composition of intestinal microbiota, and type 1 diabetes pathogenesis. In the BioBreeding rat model of type 1 diabetes, comparison of the intestinal microbial composition of diabetes prone and diabetes resistant animals found Lactobacillus species were negatively correlated with type 1 diabetes development. Two species, Lactobacillus johnsonii and L. reuteri, were isolated from diabetes resistant rats. In this study diabetes prone rats were administered pure cultures of L. johnsonii or L. reuteri isolated from diabetes resistant rats to determine the effect on type 1 diabetes development.

Methodology/principal: Findings Results Rats administered L. johnsonii, but not L. reuteri, post-weaning developed type 1 diabetes at a protracted rate. Analysis of the intestinal ileum showed administration of L. johnsonii induced changes in the native microbiota, host mucosal proteins, and host oxidative stress response. A decreased oxidative intestinal environment was evidenced by decreased expression of several oxidative response proteins in the intestinal mucosa (Gpx1, GR, Cat). In L. johnsonii fed animals low levels of the pro-inflammatory cytokine IFNgamma were correlated with low levels of iNOS and high levels of Cox2. The administration of L. johnsonii also resulted in higher levels of the tight junction protein claudin.

Conclusions: It was determined that the administration of L. johnsonii isolated from BioBreeding diabetes resistant rats delays or inhibits the onset of type 1 diabetes in BioBreeding diabetes prone rats. Taken collectively, these data suggest that the gut and the gut microbiota are potential agents of influence in type 1 diabetes development. These data also support therapeutic efforts that seek to modify gut microbiota as a means to modulate development of this disorder.

Show MeSH
Related in: MedlinePlus