PMID: 

Immunity. 2019 11 19 ;51(5):794-811. PMID: 31747581

Abstract Title: 

Western Diet and the Immune System: An Inflammatory Connection.

Abstract: 

The consumption of Western-type calorically rich diets combined with chronic overnutrition and a sedentary lifestyle in Western societies evokes a state of chronic metabolic inflammation, termed metaflammation. Metaflammation contributes to the development of many prevalent non-communicable diseases (NCDs), and these lifestyle-associated pathologies represent a rising public health problem with global epidemic dimensions. A better understanding of how modern lifestyle and Western diet (WD) activate immune cells is essential for the development of efficient preventive and therapeutic strategies for common NCDs. Here, we review the current mechanistic understanding of how the Western lifestyle can induce metaflammation, and we discuss how this knowledge can be translated to protect the public from the health burden associated with their selected lifestyle.

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PMID: 

Front Immunol. 2020 ;11:253. Epub 2020 Feb 21. PMID: 32153577

Abstract Title: 

The Impact of Dietary Components on Regulatory T Cells and Disease.

Abstract: 

The rise in the prevalence of autoimmune diseases in developed societies has been associated with a change in lifestyle patterns. Among other factors, increased consumption of certain dietary components, such as table salt and fatty acids and excessive caloric intake has been associated with defective immunological tolerance. Dietary nutrients have shown to modulate the immune response by a direct effect on the function of immune cells or, indirectly, by acting on the microbiome of the gastrointestinal tract. FOXP3regulatory T cells (Tregs) suppress immune responses and are critical for maintaining peripheral tolerance and immune homeostasis, modulating chronic tissue inflammation and autoimmune disease. It is now well-recognized that Tregs show certain degree of plasticity and can gain effector functions to adapt their regulatory function to different physiological situations during an immune response. However, plasticity of Tregs might also result in conversion into effector T cells that may contribute to autoimmune pathogenesis. Yet, which environmental cues regulate Treg plasticity and function is currently poorly understood, but it is of significant importance for therapeutic purposes. Here we review the current understanding on the effect of certain dietary nutrients that characterize Western diets in Treg metabolism, stability, and function. Moreover, we will discuss the role of Tregs linking diet and autoimmunity and the potential of dietary-based interventions to modulate Treg function in disease.

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PMID: 

Nutrients. 2020 Feb 20 ;12(2). Epub 2020 Feb 20. PMID: 32093192

Abstract Title: 

Consumption of the Total Western Diet Promotes Colitis and Inflammation-Associated Colorectal Cancer in Mice.

Abstract: 

Consumption of a Western type diet is a known risk factor for colorectal cancer. Our group previously developed the total Western diet (TWD) for rodents with energy and nutrient profiles that emulate a typical Western diet. In this study, we tested the hypothesis that consumption of the TWD would enhance colitis, delay recovery from gut injury and promote colon tumorigenesis. In multiple experiments using the azoxymethane + dextran sodium sulfate ormouse models of colitis-associated colorectal carcinogenesis (CAC), we determined that mice fed TWD experienced more severe and more prolonged colitis compared to their counterparts fed the standard AIN93G diet, ultimately leading to markedly enhanced colon tumorigenesis. Additionally, this increased tumor response was attributed to the micronutrient fraction of the TWD, and restoration of calcium and vitamin D to standard amounts ameliorated the tumor-promoting effects of TWD. Finally, exposure to the TWD elicited large scale, dynamic changes in mRNA signatures of colon mucosa associated with interferon (IFN) response, inflammation, innate immunity, adaptive immunity, and antigen processing pathways, among others. Taken together, these observations indicate that consumption of the TWD markedly enhanced colitis, delayed recovery from gut injury, and enhanced colon tumorigenesis likely via extensive changes in expression of immune-related genes in the colon mucosa.

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PMID: 

Nutrients. 2020 Feb 26 ;12(3). Epub 2020 Feb 26. PMID: 32110872

Abstract Title: 

OPK-3 from Kimchi Prevents Obesity and Modulates the Expression of Adipogenic and Pro-Inflammatory Genes in Adipose Tissue of Diet-Induced Obese Mice.

Abstract: 

Our previous study reported that lactic acid bacteria (OPK-3) isolated from kimchi ameliorated intracellular lipid accumulation in 3T3-L1 adipocyte. The current study explored potential roles ofOPK-3 (KLAB) on preventing body weight gain and its effect on the inflammatory response of adipose tissue. Male C57BL/6 mice (= 10) were divided into four groups: normal diet with distilled water (NDC), high-fat diet with distilled water (HDC), high-fat diet with L-ornithine (OTC) or high-fat diet with KLAB. The KLAB supplement resulted in significantly lower body weight, lower epididymal fat tissue mass, and lower serum and hepatic TG levels than the HDC. KLAB supplementation improved serum cytokines, and real-time polymerase chain reaction (PCR) analysis showed significantly lower inflammatory cytokine mRNA levels in epididymal adipose tissue. These results suggest that the administration of KLAB inhibits the induction of inflammation in adipose tissue along with the inhibition of weight gain. Therefore, this study demonstrates the therapeutic and beneficial value of this strain produced during the fermentation of kimchi.

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PMID: 

Korean J Gastroenterol. 2020 Mar 25 ;75(3):141-146. PMID: 32209802

Abstract Title: 

Effects of Novel Probiotics in a Murine Model of Irritable Bowel Syndrome.

Abstract: 

Background/Aims: Dysbiosis is an important factor in the pathogenesis of irritable bowel syndrome (IBS). Several studies have reported promising results using probiotics for the treatment of IBS. This study evaluated the efficacy of novel probiotics isolated from Kimchi, a Korean fermented food, and the feces of healthy Vietnamese people in a murine model of IBS.Methods: DK121 was isolated from Kimchi, andV4 andV7 were isolated from the feces of healthy Vietnamese people residing in Korea. Forty rats were allocated to receive one of the study strains, a mixture of the strains, or the vehicle. After 5 days of administration, the rats were restrained in a cage to induce IBS. The effects of the probiotics on IBS were analyzed by evaluating the stool weights and stool consistency scores.Results: The primary outcome was analyzed upon the completion of a three-week experiment. The rats in the V7 group showed lower stool weights than those in the control group at week 2 (median: 1.10 [V7] vs. 2.35 [control], p=0.04, Mann-Whitney U-test) and week 3 (median: 1.10 [V7] vs. 2.80 [control], p=0.017). The rats in the DK121 (median: 2.00, p=0.007), V7 (median: 2.00, p=0.004), and mixture (median: 1.50, p=0.001) groups showed better stool consistency scores at week 2 than the control group (median: 3.00).Conclusions: The novel probiotics have beneficial effects on defecation in a murine model of IBS. Human studies confirming the efficacy are warranted.

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PMID: 

EPMA J. 2015 ;6(1):13. Epub 2015 Jun 19. PMID: 26110044

Abstract Title: 

The role of beneficial bacteria wall elasticity in regulating innate immune response.

Abstract: 

BACKGROUND: Probiotics have great potential to contribute to development of healthy dietary regimes, preventive care, and an integrated approach to immunity-related disease management. The bacterial wall is a dynamic entity, depending on many components and playing an essential role in modulating immune response. The impact of cell wall elasticity on the beneficial effects of probiotic strains has not been sufficiently studied. The aim was to investigate the effect of lactic acid bacteria (LAB) and bifidobacteria strains on phagocytic system cells (macrophages) as related to bacterial wall elasticity, estimated using atomic force microscopy (AFM).METHODS: We conducted studies on Balb/c line mice 18-20 g in weight using lyophilized strains of LAB-Lactobacillus acidophilus IMV B-7279, Lactobacillus casei IMV B-7280, Lactobacillus delbrueckii subsp. bulgaricus IMV B-7281, and bifidobacteria-Bifidobacterium animalis VKL and Bifidobacterium animalis VKB. We cultivated the macrophages obtained from the peritoneal cavity of mice individually with the strains of LAB and bifidobacteria and evaluated their effect on macrophages, oxygen-dependent bactericidal activity, nitric oxide production, and immunoregulatory cytokines. We used AFM scanning to estimate bacterial cell wall elasticity.RESULTS: All strains had a stimulating effect on the functional activity of macrophages and ability to produce NO/NO2 in vitro. Lactobacilli strains increased the production of IL-12 and IFN-γ in vitro. The AFM demonstrated different cell wall elasticity levels in various strains of LAB and bifidobacteria. The rigidity of the cell walls among lactobacilli was distributed as follows: Lactobacillus acidophilus IMV B-7279>Lactobacillus casei IMV B-7280>Lactobacillus delbrueckii subsp. bulgaricus IMV B-7281; among the strains of bifidobacteria: B. animalis VKB>B. animalis VKL. Probiotic strain survival in the macrophages depended on the bacterial cell wall elasticity and on the time of their joint cultivation.CONCLUSION: LAB and bifidobacteria strains stimulate immune-modulatory cytokines and active oxygen and nitrogen oxide compound production in macrophages. Strains with a more elastic cell wall according to AFM data demonstrated higher resistance to intracellular digestion in macrophages and higher level of their activation. AFM might be considered as a fast and accurate method to assess parameters of probiotic strain cell wall to predict their immune-modulatory properties.

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PMID: 

Int J Mol Sci. 2015 Sep 1 ;16(9):20841-58. Epub 2015 Sep 1. PMID: 26340622

Abstract Title: 

Th17 Cells as Potential Probiotic Therapeutic Targets in Inflammatory Bowel Diseases.

Abstract: 

Inflammatory bowel diseases (IBD) are characterized by wasting and chronic intestinal inflammation triggered by various cytokine-mediated pathways. In recent years, it was shown that T helper 17 (Th17) cells are involved in the pathogenesis of IBD, which makes them an attractive therapeutic target. Th17 cells preferentially produce interleukin (IL)-17A-F as signature cytokines. The role of the interplay between host genetics and intestinal microbiota in the pathogenesis of IBD was demonstrated. Probiotics are live microorganisms that when orally ingested in adequate amounts, confer a health benefit to the host by modulating the enteric flora or by stimulating the local immune system. Several studies indicated the effectiveness of probiotics in preventing and treating IBD (ulcerative colitis, and Crohn's disease). Furthermore, there is mounting evidence of probiotics selectively targeting the Th17 lineage in the prevention and management of inflammatory and autoimmune diseases such as IBD. This review highlights critical roles of Th17 cells in the pathogenesis of IBD and the rationale for using probiotics as a novel therapeutic approach for IBD through manipulation of Th17 cells. The potential molecular mechanisms by which probiotics modulate Th17 cells differentiation and production are also discussed.

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PMID: 

Rev Med Chil. 2016 Jul ;144(7):910-6. PMID: 27661555

Abstract Title: 

[The role of gut microbiota in the regulation of the immune response].

Abstract: 

The gastrointestinal tract hosts around 10(14) bacterial microorganisms, in a constantly growing density from the stomach to the distal colon. This microbiota is composed by more than 500 species of bacteria, which are quickly acquired after birth, fairly stable during the host’s life, and essential for human homeostasis. These bacteria have important functions, such as stimulating the immune system, protecting the host from invading bacteria and viruses, and improving digestion, especially of complex carbohydrates. Also, the gut microbiota interacts directly with the immune system. However, the interaction of the intestinal epithelium and its microbiota with the immune system has yet to be fully understood. Secretory immunoglobulin A, produced by the plasma cells in Peyer’s patches and in the lamina propria, maintains non-invasive commensal bacteria and neutralize invasive pathogens. Dendritic cells migrate from the lamina propria of the secondary lymphoid organs to regulate gut immunity. They also have a key role maintaining luminal IgA and inducing the growth of regulatory T cells. Dendritic cells supervise the gut microenvironment too, keeping an immunological equilibrium and tolerance. The importance of the gut microbiota in regulating the immune system lies mostly in the homeostasis-or positive equilibrium. Thus, many diseases are a consequence of poor interactions or a loss of this equilibrium.

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PMID: 

PLoS One. 2019 ;14(11):e0216184. Epub 2019 Nov 6. PMID: 31693670

Abstract Title: 

Lactobacillus rhamnosus Lcr35 as an effective treatment for preventing Candida albicans infection in the invertebrate model Caenorhabditis elegans: First mechanistic insights.

Abstract: 

The increased recurrence of Candida albicans infections is associated with greater resistance to antifungal drugs. This involves the establishment of alternative therapeutic protocols, such as probiotic microorganisms whose antifungal potential has already been demonstrated using preclinical models (cell cultures, laboratory animals). Understanding the mechanisms of action of probiotic microorganisms has become a strategic need for the development of new therapeutics for humans. In this study, we investigated the prophylactic anti-C. albicans properties of Lactobacillus rhamnosus Lcr35® using the in vitro Caco-2 cell model and the in vivo Caenorhabditis elegans model. In Caco-2 cells, we showed that the strain Lcr35® significantly inhibited the growth (~2 log CFU.mL-1) and adhesion (150 to 6,300 times less) of the pathogen. Moreover, in addition to having a pro-longevity activity in the nematode (+42.9%, p = 3.56.10-6), Lcr35® protects the animal from the fungal infection (+267% of survival, p

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PMID: 

J Microbiol Biotechnol. 2019 Jan 28 ;29(1):160-170. PMID: 30415527

Abstract Title: 

Immunomodulatory Properties ofNC8 Expressing an Anti-CD11c Single-Chain Fv Fragment.

Abstract: 

The lactic acid bacteria species() has been used extensively for vaccine delivery. Considering to the critical role of dendritic cells in stimulating host immune response, in this study, we constructed a novel CD11c-targetingstrain with surface-displayed variable fragments of anti-CD11c, single-chain antibody (scFv-CD11c). The newly designedstrain, named 409-aCD11c, could adhere and invade more efficiently to bone marrow-derived DCs (BMDCs) in vitro due to the specific interaction between scFv-CD11c and CD11c located on the surface of BMDCs. After incubation with BMDCs, the 409-aCD11c strain harboring a eukaryotic vector pValac-GFP could lead to more efficient expression of GFP compared with wild-type strains shown by flow cytometry analysis, indicating the enhanced translocation of pValac-GFP fromto BMDCs. Similar results were also observed in an in vivo study, which showed that oral administration resulted in efficient expression of GFP in both Peyer's patches (PP) and mesenteric lymph nodes (MLNs) within 7 days after the last administration. In addition, the CD11c-targeting strain significantly promoted the differentiation and maturation of DCs, the differentiation of IL-4⁺ and IL-17A⁺ T helper (Th) cells in MLNs, as well as production of B220⁺ IgA⁺ B cells in the PP. In conclusion, this study developed a novel DC-targetingstrain which could increase the ability to deliver eukaryotic expression plasmid to host cells, indicating a promising approach for vaccine study.

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