Elsevier

Nutrition

Volume 31, Issues 7–8, July–August 2015, Pages 1000-1007
Nutrition

Basic nutritional investigation
Lactobacillus casei CRL 431 administration decreases inflammatory cytokines in a diet-induced obese mouse model

https://doi.org/10.1016/j.nut.2015.02.006Get rights and content

Highlights

  • The administration of the probiotic Lactobacillus casei CRL 431 to diet-induced obese mice decreased the inflammatory state in the small intestine, liver, and adipose tissues.

  • Probiotic administration, especially as fermented milk was associated to decrease of proinflammatory cytokines, such as interferon-γ, tumor necrosis factor-α, interleukin (IL)-6 and IL-17 in the small intestine and liver of diet-induced obese mice.

  • Probiotic administration also was related to fewer immune-infiltrating cells in the liver of diet-induced obese mice.

  • L. casei CRL 431 administered as suspension and mainly as fermented milk was able to reduce the secretion of IL-6 and monocyte chemoattractant protein-1 by the adipocytes isolated from diet-induced obese mice, maintaining a regulated immune response, through the secretion of IL-10.

Abstract

Objectives

Obesity is a chronic disease associated with an inflammatory process in which cytokines play an important role. Probiotic microorganisms have been associated with modulation of the host immune system. The aim of this study was to evaluate the influence of the probiotic bacterium Lactobacillus casei CRL 431 on the cytokine response in a model of mice under high-fat diet (HFD) conditions.

Methods

BALB/c mice received a conventional balanced diet or an HFD. The test groups received milk, milk fermented by L. casei (FM), or L. casei as suspension in the drinking water. Proinflammatory and regulatory cytokine producer cells were evaluated in the small intestine and liver; the cytokine levels in the intestinal fluids were also evaluated. The percentages of immune cells as macrophages (F4/80), NKT, CD4+, CD8+ populations were determined in the liver. Adipocytes were also isolated and cultured to evaluate cytokines and the chemokine monocyte chemoattractant protein (MCP)-1 produced by them.

Results

The administration of probiotic L. casei CRL 431 exerted an anti-inflammatory response in mice fed an HFD, evidenced mainly by decreasing proinflammatory cytokines, such as interleukin (IL)-6, IL-17, and tumor necrosis factor-α. Probiotic administration also was associated with fewer immune-infiltrating cells in the liver of mice that received the HFD and decreased secretion of MCP-1 by the adipocytes. This last observation could be associated with less macrophage accumulation in the adipose tissues, which is characteristic in the obese host and contributes to maintaining the inflammatory response in this organ. The results obtained show an anti-inflammatory effect of L. casei CRL 431 when it is administered as a supplement of the HFD in a mouse model.

Introduction

Obesity is defined as a chronic disease characterized by an excessive accumulation of fat or adipose tissue hypertrophy. Obesity has become a serious public health problem that is increasing and has reached epidemic proportions worldwide [1]. It has a multifactorial origin and is strongly associated with metabolic syndrome (MetS), causing different diseases such as cardiovascular diseases, type 2 diabetes mellitus, and sleep apnea [2], [3]. Obesity is considered an inflammatory process in which the adipose tissue plays an important role [4]. Poor eating habits and sedentary lifestyles are associated with obesity-related diseases. People tend to choose some dietary supplements that, in addition to their nutritional properties, can exert some effect on their health. In this context, products containing probiotic microorganisms often are included in the daily diet.

Probiotics are defined as live microorganisms that, when administered in adequate amounts, confer a health benefit on the host [5]. Previous studies have described the capacity of certain probiotic microorganisms or fermented products to exert a beneficial balance in the gut microbiota, which improves the immunologic status of the host and modulates the cytokine release in the lamina propria of the small intestine [6], [7], [8]. The beneficial effects of certain probiotics on body weight and on some immunologic and metabolic parameters were evaluated in animal models of obesity, diabetes, and hyperlipidemia [9], [10], [11]. It also has been reported that probiotic administration to obese hosts improves gut microbiota [12], [13], modulates genes associated with metabolism and inflammation in the liver and adipose tissue [14], and improves symptoms associated with MetS [15].

Supplementing the diet with probiotics could be a possible alternative to combating obesity and other disorders associated to it, especially those caused by the anti-inflammatory effects exerted by these microorganisms [16], [17].

Lactobacillus casei CRL 431, a probiotic bacterium that affects the intestinal immune system, has been extensively studied using murine models [18], [19], [20], [21].

Recently, we evaluated the effect of the administration of L. casei CRL 431 as a supplementation for a high-fat diet (HFD) in a mouse model [22]. It was demonstrated that L. casei CRL 431 administration as suspension or as fermented milk (FM) decreased the body weight and biochemical parameters in blood that are associated with MetS. This beneficial effect was associated with the improvement of gut microbiota by increasing bifidobacteria and by avoiding a decrease of bacteroides. Both bacterial populations were found diminished in mice receiving HFDs [23]. The histology of liver and small intestine, affected by the HFD intake, were also improved in mice that received L. casei CRL431 [22].

The aim of this study was to evaluate the influence of the probiotic bacterium L. casei CRL 431 and its FM on the cytokine response (in small intestine, liver, and adipocytes) when they are administered as diet supplements for mice fed an HFD. We hypothesized that the proinflammatory cytokines, which are increased during the diet-induced obesity, can be modulated by the probiotic administration.

Section snippets

Bacterial strain and fermented milk

L. casei CRL 431 was obtained from the CERELA Culture Collection (San Miguel de Tucumán, Argentina). Overnight cultures were grown at 37°C in 5 mL sterile Mann-Rogosa-Sharp (MRS) broth (Britania, Buenos Aires, Argentina). The cells were harvested by centrifugation at 5000g for 10 min, washed three times with fresh phosphate-buffered saline (PBS) solution and then resuspended in 5 mL of sterile 10% (wt/vol) nonfat milk. This bacterial suspension was diluted 1:30 in water and administered ad

Fermented milk or L. casei administration as suspension modulate the number of cytokine and TLR-5–positive cells in the lamina propria of the small intestine

No significant differences in the number of IFN-γ–positive cells in the small intestine were observed between the different study groups (Fig. 1A).

The number of TNF-α–positive cells increased significantly (P < 0.05) in the nonobese mice that consumed milk compared with the NC group. The other diet supplements did not modify the number of TNF-α–positive cells. In mice fed the HFD, the number of TNF-α–positive cells was significantly increased in control mice (OC) and in the mice from the

Discussion

In this study, we analyzed the modifications of cytokine profiles in the small intestine, liver, and adipose tissue exerted by the administration of the probiotic strain L. casei CRL 431 as suspension or contained in FM, considering the positive effect observed previously in the body weight and clinical parameters in mice receiving probiotic [22]. In that work, it was demonstrated that mice given a balanced diet had a 50% ± 2% body weight gain in the live body during the 2 mo of the experiment.

Conclusion

The results obtained in this study showed that probiotic supplementation to hosts susceptible to developing obesity can be effective, and that this effect is mainly related to the anti-inflammatory capacity of the selected probiotic strain.

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    This work was financially supported by Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET, PIP 0652 and 1071) and CIUNT (Universidad Nacional de Tucumán, CIUNT 26/D442), Argentina. INN, CMG, and AdMdL carried out the microbiologic work, the animal studies, and the immunologic determinations; performed the statistical analyses; and prepared the figures. GP conceived of the study. CMG, AdMdL, and GP designed the experiments. INN, CMG, AdMdL, and GP wrote the draft of the manuscript. All authors read and approved the final version of the manuscript. The authors have no conflicts of interest to declare.

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