Basic nutritional investigationLactobacillus casei CRL 431 administration decreases inflammatory cytokines in a diet-induced obese 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.
References (40)
- et al.
Obesity
Lancet
(2005) - et al.
Association of bodyweight with total mortality and with cardiovascular events in coronary artery disease: a systematic review of cohort studies
Lancet
(2006) - et al.
Strain-dependent induction of cytokine profiles in the gut by orally administered Lactobacillus strains
Vaccine
(2000) - et al.
Antidiabetic effect of probiotic dahi containing Lactobacillus acidophilus and Lactobacillus casei in high fructose fed rats
Nutrition
(2007) - et al.
Probiotics improve high fat diet-induced hepatic steatosis and insulin resistance by increasing hepatic NKT cells
J Hepatol
(2008) - et al.
Probiotics: interaction with gut microbiome and antiobesity potential
Nutrition
(2013) - et al.
Yoghurt consumption regulates the immune cells implicated in acute intestinal inflammation and prevents the recurrence of the inflammatory process in a mouse model
J Food Prot
(2011) - et al.
Dietary calcium attenuation of body fat gain during high-fat feeding in mice
J Nutr Biochem
(2008) - et al.
IL-17 in obesity and adipogenesis
Cytokine Growth Factor Rev
(2010) - et al.
Regulatory T cells in obesity: the leptin connection
Trends Mol Med
(2010)
Current and future drugs targeting one class of innate immunity receptors: the toll-like receptors
Drug Discov Today
Adipokines: inflammation and the pleiotropic role of white adipose tissue
Br J Nutr
Impact of a probiotic fermented milk in the gut ecosystem and in the systemic immunity using a non-severe protein-energy-malnutrition model in mice
BMC Gastroenterol
Lactobacilli differentially modulate expression of cytokines and maturation surface markers in murine dendritic cells
J Immunol
Milk fermented by Lactobacillus gasseri SBT2055 influences adipocyte size via inhibition of dietary fat absorption in Zucker rats
Br J Nutr
Intestinal microbiota, relevance to obesity and modulation by prebiotics and probiotics
Nutr Hosp
Supplementation of Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032 in diet-induced obese mice is associated with gut microbial changes and reduction in obesity
PLoS One
Bifidobacterium adolescentis supplementation ameliorates visceral fat accumulation and insulin sensitivity in an experimental model of the metabolic syndrome
Br J Nutr
Cited by (43)
Role of intestinal probiotics in the modulation of lipid metabolism: implications for therapeutic treatments
2023, Food Science and Human WellnessGut mucosal and adipose tissues as health targets of the immunomodulatory mechanisms of probiotics
2021, Trends in Food Science and TechnologyCitation Excerpt :Probiotics evaluated for their immunomodulatory effects on gut/adipose tissue inflammation are summarized in Table 2. Hence, their role in inflammation-mediated metabolic diseases has been studied in cell lines (Belguesmia et al., 2016; Fabersani et al., 2017; Torres, Fabersani, Marquez, & Gauffin-Cano, 2019), animal models (An et al., 2011; Bagarolli et al., 2017; Calcinaro et al., 2005; Cano et al, 2012, 2013; Chen, Wang, Li, & Wang, 2011; Holowacz et al., 2015; Karlsson et al., 2012; Kim, Park, Kim, Kim, & Hyun, 2013; Lee et al., 2006; Ma, Hua, & Li, 2008; Miyoshi, Ogawa, Higurashi, & Kadooka, 2014; Núñez, Galdeano, de LeBlanc, & Perdigón, 2015; Okubo, Takemura, Yoshida, & Sonoyama, 2013; Park et al, 2013, 2015; Plaza-Diaz et al., 2014; Poutahidis et al., 2013; Ritze et al., 2014; Sakai et al., 2013; Takemura, Okubo, & Sonoyama, 2010; Toral et al., 2014; Wang, Wang, & Gershwin, 2015; Yoo et al., 2013; Zarfeshani et al., 2011; Zhang et al., 2017) and clinical trials (Bernini et al., 2016; Ghanei et al., 2018; Kadooka et al., 2010; Malaguarnera et al., 2012; Mazloom, Yousefinejad, & Dabbaghmanesh, 2013; Sanchez et al., 2014; Stenman et al., 2016; Zarrati et al., 2014). Generally, studies have shown that both anti-inflammatory and anti-obesity properties exerted by lactic acid bacteria in adipose tissue display interconnected mechanisms, while they are strain-specific, prevailing in particular strains of Lactobacillus and Bifidobacterium genera (Torres et al., 2019).
Intervention of five strains of Lactobacillus on obesity in mice induced by high-fat diet
2020, Journal of Functional FoodsCitation Excerpt :Lactobacillus have been reported to have many probiotic functions: lowering blood lipids, protecting the cardiovascular system, and alleviating the symptoms of obesity (Cerdó, García-Santos, G Bermúdez, & Campoy, 2019). Many previous studies have shown that probiotics such as Lactobacillus rhamnosus, Lactobacillus brevis, Lactobacillus plantarum, and Lactobacillus paracasei have lipid-lowering effects to alleviate obesity (Núñez, Galdeano, de LeBlanc, & Perdigón, 2015; Soyoung Park et al., 2017; Salehipour et al., 2017). The results of different types of probiotics for the treatment of obesity may differ due to differences in experimental methods, dose intake, duration, and inclusion population (Cerdó, García-Santos, Bermúdez, & M., & Campoy, C. , 2019).
Modulation of intestinal microbiota and immunometabolic parameters by caloric restriction and lactic acid bacteria
2019, Food Research InternationalThe impact of probiotics’ administration on glycemic control, body composition, gut microbiome, mitochondria, and other hormonal signals in adolescents with prediabetes – A randomized, controlled trial study protocol
2018, Contemporary Clinical Trials CommunicationsCitation Excerpt :The administration of probiotics may activate different metabolic pathways, which may affect the metabolism of the adipose tissue. In rat models, the administration of probiotics has demonstrated anti-inflammatory effects [77], or in some cases, even loss of weight, and fat mass [78]. Body composition analysis has been proven to be an accurate means of providing evidence for health status [9,53].
Adipose tissue extrinsic factor: Obesity-induced inflammation and the role of the visceral lymph node
2018, Physiology and BehaviorCitation Excerpt :For example, high fat diet (HFD) feeding increases tumor necrosis factor α (TNFα) expression and nuclear factor κβ (NF-κβ) activation, markers of pro-inflammation, in the small intestines of mice [33]. Consistent with this others demonstrate that HFD increases TNFα concentration within the lamina propria of the small intestines as well as other pro-inflammatory markers such as interleukin 6 and 17 (IL6 and 17) [34]. Epithelial cells also release IL6, as well as growth-related oncogene/cytokine-induced neutrophil chemoattractant-1 (GRO/CINC-1; stimulates locomotion and activation of neutrophils) in the presence of long chain fatty acids [35].
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.