Lactobacillus bulgaricus OLL1181 activates the aryl hydrocarbon receptor pathway and inhibits colitis

Increasing evidence suggests that the aryl hydrocarbon receptor (AhR) pathway has an important role in the regulation of inflammatory responses. Most recently, we have shown that the activation of the AhR pathway by a potent AhR agonist inhibits the development of dextran sodium sulfate (DSS)-induced colitis, a model of human ulcerative colitis, by the induction of prostaglandin E2 (PGE2) in the large intestine. Because several strains of probiotic lactic acid bacteria have been reported to inhibit DSS-induced colitis by unidentified mechanisms, we hypothesized that particular strains of lactic acid bacterium might have the potential to activate the AhR pathway, thereby inhibiting DSS-induced colitis. This study investigated whether there are specific lactic acid bacterial strains that can activate the AhR pathway, and if so, whether this AhR-activating potential is associated with suppression of DSS-induced colitis. By using AhR signaling reporter cells, we found that Lactobacillus bulgaricus OLL1181 had the potential to activate the AhR pathway. OLL1181 also induced the mRNA expression of cytochrome P450 family 1A1 (CYP1A1), a target gene of the AhR pathway, in human colon cells, which was inhibited by the addition of an AhR antagonist, α-naphthoflavon (αNF). In addition, mice treated orally with OLL1181 showed an increase in CYP1A1 mRNA expression in the large intestine and amelioration of DSS-induced colitis. Thus, OLL1181 can induce activation of the intestinal AhR pathway and inhibit DSS-induced colitis in mice. This strain of lactic acid bacterium has therefore the potential to activate the AhR pathway, which may be able to suppress colitis

Randomized trial of amino acid mixture combined with physical activity promotion for abdominal fat reduction in overweight adults

Purpose: The purpose of this study was to test the efficacy of arginine, alanine, and phenylalanine mixture (A-mix) ingestion at 1,500 mg/day in combination with the promotion of physical activity for abdominal fat reduction in overweight adults.Methods: A placebo-controlled, double-blind, parallel-group, randomized trial for 12 weeks combined with a 4-week follow-up period was conducted at a single center in Minato-ku, Tokyo, Japan, between December 2016 and May 2017. Data were analyzed between June and August 2017. The study participants were 200 overweight adults within the age range of 20–64 years. The participants were randomly assigned to the A-mix group (n=100) or a placebo group (n=100) and were administered 500 mL of test beverage containing 1,500 or 0 mg of A-mix, respectively, for 12 weeks. All participants maintained a physically active lifestyle between week 0 and week 12 through monthly sessions of physical activity. The primary outcomes were the 12-week changes in the abdominal total, subcutaneous, and visceral fat areas, as assessed by computed tomography.Results: Of the 200 enrolled participants, 199 (99%) accomplished the 12-week intervention and 4-week follow-up period. The per-protocol-based analysis for 194 participants demonstrated that the abdominal total fat area decreased significantly in the A-mix group compared with that in the placebo group (difference, 10.0 cm2; 95% confidence interval [CI]: 0.4–19.6 cm2; P=0.041). Comparable outcomes were obtained for the abdominal subcutaneous fat area (difference, 7.4 cm2; 95% CI: 0.1–14.7 cm2; P=0.047). No study-related unfavorable events occurred.Conclusion: A-mix supplementation in combination with physical activity promotion facilitated abdominal fat reduction in overweight adults

Immunobiotic Lactobacillus jensenii as immune-health promoting factor to improve growth performance and productivity in post-weaning pigs

Background: Immunoregulatory probiotics (immunobiotics) have been proposed to improve piglets' immune system to avoid intestinal infections and reduce unproductive inflammation after weaning. Previously, it was demonstrated that Lactobacillus jensenii TL2937 (LjTL2937) attenuated the inflammatory response triggered by activation of Toll-like receptor 4 (TLR-4) in porcine intestinal epithelial (PIE) cells and antigen presenting cells (APCs) from porcine Peyer's patches (PP).Objective: In view of the critical importance of PIE-APCs interactions in the regulation of intestinal immune responses, we aimed to examine the effect of LjTL2937 on activation patterns of APCs from swine PPs in co-cultures with PIE cells. In addition, we investigated whether LjTL2937 was able to beneficially modulate intestinal immunity of piglets after weaning to improve immune-health status.Results: Stimulation of PIE-APCs co-cultures with LjTL2937 increased the expression of MHC-II, CD80/86, IL-10, and Bcl-3 in CD172a+CD11R1- and CD172a+CD11R1high APCs. In addition, the TL2937 strain caused the upregulation of three negative regulators of TLR4 in PIE cells: MKP-1, Bcl-3 and A20. These changes significantly reduced the inflammatory response triggered by TLR4 activation in PIE-APCs co-cultures. The in vivo experiments using castrated male piglets (crossbreeding (LWD) with Landrace (L), Large Yorkshire (W) and Duroc (D))of 3 weeks of age demonstrated that feeding with LjTL2937 significantly reduced blood complement activity and C reactive protein concentrations while no changes were observed in blood leukocytes, ratio of granulocytes to lymphocyte numbers, macrophages' activity and antibody levels. In addition, treatment with LjTL2937 significantly improved growth performance and productivity, and increased carcass quality.Conclusions: We demonstrated that the use of immunobiotics strains like LjTL2937, as supplemental additives for piglets feedings, could be used as a strategy to maintain and improve intestinal homeostasis; that is important for the development of the pig and for health and performance throughout the productive life of the animal.Fil: Suda, Yoshihito. Miyagi University. Department of Food, Agriculture and Environment; JapónFil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Takahashi, Yu. Miyagi University. Department of Food, Agriculture and Environment; JapónFil: Hosoya, Shoichi. Tohoku University. Graduate School of Agricultural Science. Laboratory of Animal Products Chemistry. Food and Feed Immunology Group; JapónFil: Tomosada, Yohsuke. Tohoku University. Graduate School of Agricultural Science. Laboratory of Animal Products Chemistry. Food and Feed Immunology Group; JapónFil: Tsukida, Kohichiro. Tohoku University. Graduate School of Agricultural Science. Laboratory of Animal Products Chemistry. Food and Feed Immunology Group; JapónFil: Shimazu, Tomoyuki. Tohoku University. Graduate School of Agricultural Science. Laboratory of Animal Breading and Genetics ; JapónFil: Aso, Hisashi. Tohoku University. Graduate School of Agricultural Science. Cell Biology Laboratory; JapónFil: Tohno, Masanori. National Institute of Livestock and Grassland Science; JapónFil: Ishida, Mitsuharu. Miyagi University. Department of Food, Agriculture and Environment; JapónFil: Makino, Seiya. No especifíca;Fil: Ikegami, Shuji. No especifíca;Fil: Kitazawa, Haruki. Tohoku University. Graduate School of Agricultural Science. Laboratory of Animal Products Chemistry. Food and Feed Immunology Group; Japó

Immunobiotic lactic acid bacteria beneficially regulate immune response triggered by poly(I:C) in porcine intestinal epithelial cells

This study analyzed the functional expression of TLR3 in various gastrointestinal tissues from adult swine and shows that TLR3 is expressed preferentially in intestinal epithelial cells (IEC), CD172a+CD11R1high and CD4+ cells from ileal Peyer's patches. We characterized the inflammatory immune response triggered by TLR3 activation in a clonal porcine intestinal epitheliocyte cell line (PIE cells) and in PIE-immune cell co-cultures, and demonstrated that these systems are valuable tools to study in vitro the immune response triggered by TLR3 on IEC and the interaction between IEC and immune cells. In addition, we selected an immunobiotic lactic acid bacteria strain, Lactobacillus casei MEP221106, able to beneficially regulate the anti-viral immune response triggered by poly(I:C) stimulation in PIE cells. Moreover, we deepened our understanding of the possible mechanisms of immunobiotic action by demonstrating that L. casei MEP221106 modulates the interaction between IEC and immune cells during the generation of a TLR3-mediated immune response

Advanced application of bovine intestinal epithelial cell line for evaluating regulatory effect of lactobacilli against heat-killed enterotoxigenicEscherichia coli-mediated inflammation

Background: Previously, a bovine intestinal epithelial cell line (BIE cells) was successfully established. This work hypothesized that BIE cells are useful in vitro model system for the study of interactions of microbial- or pathogenassociated molecular patterns (MAMPs or PAMPs) with bovine intestinal epithelial cells and for the selection of immunoregulatory lactic acid bacteria (LAB). Results: All toll-like receptor (TLR) genes were expressed in BIE cells, being TLR4 one of the most strongly expressed. We demonstrated that heat-stable PAMPs of enterotoxigenic Escherichia coli (ETEC) significantly enhanced the production of IL-6, IL-8, IL-1! and MCP-1 in BIE cells by activating both NF-"B and MAPK pathways. We evaluated the capacity of several lactobacilli strains to modulate heat-stable ETEC PAMPs-mediated inflammatory response in BIE cells. Among these strains evaluated, Lactobacillus casei OLL2768 attenuated heat-stable ETEC PAMPs-induced pro-inflammatory response by inhibiting NF-"B and p38 signaling pathways in BIE cells. Moreover, L. casei OLL2768 negatively regulated TLR4 signaling in BIE cells by up-regulating Toll interacting protein (Tollip) and B-cell lymphoma 3-encoded protein (Bcl-3). Conclusions: BIE cells are suitable for the selection of immunoregulatory LAB and for studying the mechanisms involved in the protective activity of immunobiotics against pathogen-induced inflammatory damage. In addition, we showed that L. casei OLL2768 functionally modulate the bovine intestinal epithelium by attenuating heat-stable ETEC PAMPs-induced inflammation. Therefore L. casei OLL2768 is a good candidate for in vivo studying the protective effect of LAB against intestinal inflammatory damage induced by ETEC infection or heat-stable ETEC PAMPs challenge in the bovine host.Fil: Takanashi, Naoya. Food and Feed Immunology Group. Laboratory of Animal Products Chemistry. Graduate School of Agricultural Science. Tohoku University; Japan;Fil: Tomosada, Yohsuke. Food and Feed Immunology Group. Laboratory of Animal Products Chemistry. Graduate School of Agricultural Science. Tohoku University; Japan;Fil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Tucuman. Centro de Referencia Para Lactobacilos (i); Food and Feed Immunology Group. Laboratory of Animal Products Chemistry. Graduate School of Agricultural Science. Tohoku University; Japan;Fil: Murata, Kozue. Food and Feed Immunology Group. Laboratory of Animal Products Chemistry. Graduate School of Agricultural Science. Tohoku University; Japan;Fil: Takahashi, Takuya. Food and Feed Immunology Group. Laboratory of Animal Products Chemistry. Graduate School of Agricultural Science. Tohoku University; Japan;Fil: Chiba, Eriko. Food and Feed Immunology Group. Laboratory of Animal Products Chemistry. Graduate School of Agricultural Science. Tohoku University; Japan;Fil: Tohno, Masanori. Food and Feed Immunology Group. Laboratory of Animal Products Chemistry. Graduate School of Agricultural Science. Tohoku University; Japan; National Agriculture and Food Research Organization. National Institute of Livestock and Grassland Science; Japan.;Fil: Tomoyuki Shimazu. Food and Feed Immunology Group. Laboratory of Animal Products Chemistry. Graduate School of Agricultural Science. Tohoku University; Japan; Laboratory of Animal Breading and Genetics. Graduate School of Agricultural Science; Japan.;Fil: Aso, Hisashi. Cell Biology Laboratory, Graduate School of Agricultural Science. Tohoku University; Japan.;Fil: Suda, Yoshihito. Department of Food, Agriculture and Environment. Miyagi University; Japan.;Fil: Ikegami, Shuji. Division of Research and Development. Food Science Institut. Meiji Dairies CoOdawara; Japan;Fil: Itoh, Hiroyuki. Division of Research and Development. Food Science Institut. Meiji Dairies CoOdawara; Japan;Fil: Kawai, Yasushi. Food and Feed Immunology Group. Laboratory of Animal Products Chemistry. Graduate School of Agricultural Science. Tohoku University; Japan;Fil: Tadao Saito. Food and Feed Immunology Group. Laboratory of Animal Products Chemistry. Graduate School of Agricultural Science. Tohoku University; Japan;Fil: Alvarez, Gladis Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); Argentina;Fil: Kitazawa, Haruki. Food and Feed Immunology Group. Laboratory of Animal Products Chemistry. Graduate School of Agricultural Science. Tohoku University; Japan

Dose-ranging pilot randomized trial of amino acid mixture combined with physical activity promotion for reducing abdominal fat in overweight adults

Objective: The objective of this study was to determine the effective dose of an amino acid mixture comprising arginine, alanine, and phenylalanine combined with physical activity promotion in reducing abdominal fat among overweight adults.Methods: A 12-week randomized, double-blind, placebo-controlled, dose-ranging, pilot trial was conducted in Mito, Japan, from January through April 2016, and the data were analyzed from May through November 2016. The study participants were 35 overweight adults, aged 20–64 years, with no regular exercise habit. Participants were randomly assigned to high-dose (3,000 mg/d, n=9), medium-dose (1,500 mg/d, n=9), low-dose (750 mg/d, n=8), or placebo (0 mg/d, n=9) groups, and the test beverage containing the amino acid mixture or placebo was administered for 12 weeks. All participants maintained a physically active lifestyle during the study period through monthly physical activity promotion sessions and smartphone-based self-monitoring with wearable trackers. Primary outcomes were changes in abdominal total, subcutaneous, and visceral fat areas, assessed by computed tomography.Results: Of the 35 enrolled participants, 32 completed the 12-week follow-up visit. The intention-to-treat analysis revealed that the changes in abdominal total fat area were −14.6 cm2 (95% confidence interval [CI], −39.6 cm2 to 10.4 cm2), −25.3 cm2 (95% CI, −71.0 cm2 to 20.3 cm2), −23.2 cm2 (95% CI, −48.0 cm2 to 1.6 cm2), and −12.5 cm2 (95% CI, −29.1 cm2 to 4.0 cm2) in the high-dose, medium-dose, low-dose, and placebo groups, respectively. Similar results were obtained for visceral and subcutaneous fat areas. No study-related adverse events were reported.Conclusion: Compared with placebo, a medium or low dose of the amino acid mixture may facilitate abdominal fat reduction among overweight adults. A larger randomized trial with sufficient statistical power should be implemented to validate the effectiveness of this supplement

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements