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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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Kaplan-Meier plot depicting development of T1D in BB-DP rats.Rats fed A) pre-weaning or B) post-weaning with L. johnsonii N6.2 (short dashed line), or L. reuteri TD1 (long dashed line) compared to the PBS fed control (solid line) N = 10 per group.
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pone-0010507-g002: Kaplan-Meier plot depicting development of T1D in BB-DP rats.Rats fed A) pre-weaning or B) post-weaning with L. johnsonii N6.2 (short dashed line), or L. reuteri TD1 (long dashed line) compared to the PBS fed control (solid line) N = 10 per group.

Mentions: Lactobacillus strains isolated from BB-DR rats were administered to BB-DP rats to analyze their effect on T1D development. L. reuteri TD1 or L. johnsonii N6.2 suspensions (1×108 CFU per animal) were administered individually daily by oral gavage i) pre-weaning to 1 day old BB-DP rats during mother feeding and ii) post-weaning to 21 day old BB-DP rats (Fig. 1). The pre-weaning administration of Lactobacillus did not modify the rate of T1D development, however the post-weaning administration of L. johnsonii N6.2 decreased the incidence of T1D compared to the control animal group (BB-DP, N = 10, P<0.1). A more significant difference was observed when comparing the L. johnsonii N6.2 fed group to the L. reuteri TD1 fed group (P<0.04). While disease incidence in L. johnsonii fed animals decreased, the L. reuteri fed group showed a similar behavior as the control group (Fig. 2). The delay in T1D onset was specific to L. johnsonii fed animals. As a result, in the remainder of the study we compared the responses referring to three groups: (i) L. johnsonii fed group (includes only healthy animals), (ii) healthy controls, and (iii) diabetic animals (includes animals from both the diabetic control and L. johnsonii fed groups that developed T1D).


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)

Kaplan-Meier plot depicting development of T1D in BB-DP rats.Rats fed A) pre-weaning or B) post-weaning with L. johnsonii N6.2 (short dashed line), or L. reuteri TD1 (long dashed line) compared to the PBS fed control (solid line) N = 10 per group.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0010507-g002: Kaplan-Meier plot depicting development of T1D in BB-DP rats.Rats fed A) pre-weaning or B) post-weaning with L. johnsonii N6.2 (short dashed line), or L. reuteri TD1 (long dashed line) compared to the PBS fed control (solid line) N = 10 per group.
Mentions: Lactobacillus strains isolated from BB-DR rats were administered to BB-DP rats to analyze their effect on T1D development. L. reuteri TD1 or L. johnsonii N6.2 suspensions (1×108 CFU per animal) were administered individually daily by oral gavage i) pre-weaning to 1 day old BB-DP rats during mother feeding and ii) post-weaning to 21 day old BB-DP rats (Fig. 1). The pre-weaning administration of Lactobacillus did not modify the rate of T1D development, however the post-weaning administration of L. johnsonii N6.2 decreased the incidence of T1D compared to the control animal group (BB-DP, N = 10, P<0.1). A more significant difference was observed when comparing the L. johnsonii N6.2 fed group to the L. reuteri TD1 fed group (P<0.04). While disease incidence in L. johnsonii fed animals decreased, the L. reuteri fed group showed a similar behavior as the control group (Fig. 2). The delay in T1D onset was specific to L. johnsonii fed animals. As a result, in the remainder of the study we compared the responses referring to three groups: (i) L. johnsonii fed group (includes only healthy animals), (ii) healthy controls, and (iii) diabetic animals (includes animals from both the diabetic control and L. johnsonii fed groups that developed T1D).

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