Low Interleukin 10 Production at Birth Is a Risk Factor for Atopic Dermatitis in Neonates with Bifidobacterium Colonization.

BACKGROUND: Altered regulatory immune responses to microbial stimuli and intestinal colonization of beneficial bacteria early in life may contribute to the development of allergic diseases (e.g., atopic dermatitis [AD]). However, few reports have investigated these factors simultaneously. The purpose of this study was to analyze neonatal immune responses to microbial stimuli as well as intestinal colonization of beneficial bacteria, in relation to the development of AD in a birth cohort. METHODS: Pregnant women were recruited, and their infants were followed up until 7 months of age. Levels of interleukin (IL)-10 released from cord-blood mononuclear cells (CBMCs) stimulated with heat-killed gram-positive bacteria (Bifidobacterium bifidum and Lactobacillus rhamnosus GG) and Lactobacillus-derived peptidoglycan were measured. Fecal Bifidobacterium counts at 4 days and 1 month were quantified using real-time polymerase chain reaction. The development of AD was determined by means of a questionnaire at 7 months of age. RESULTS: The levels of released IL-10 were significantly lower in infants with AD (n = 17) than in infants without AD (n = 53) for all stimuli. In infants with fecal Bifidobacterium, the incidence of AD was inversely associated with the release of IL-10 from cord blood mononuclear cells. CONCLUSION: Our findings suggest that impaired IL-10 production in response to microbial stimuli at birth may be associated with an increased risk of developing infantile AD, even in infants with early colonization of intestinal bifidobacteria.

Combination of aerobic exercise and an arginine, alanine, and phenylalanine mixture increases fat mobilization and ketone body synthesis.

During exercise, blood levels of several hormones increase acutely. We hypothesized that consumption of a specific combination of amino acids (arginine, alanine, and phenylalanine; A-mix) may be involved in secretion of glucagon, and when combined with exercise may promote fat catabolism. Ten healthy male volunteers were randomized in a crossover study to ingest either A-mix (3 g/dose) or placebo (3 g of dextrin/dose). Thirty minutes after ingesting, each condition subsequently performed workload trials on a cycle ergometer at 50% of maximal oxygen consumption for 1 h. After oral intake of A-mix, the concentrations of plasma ketone bodies and adrenalin during and post-exercise were significantly increased. The area under the curve for glycerol and glucagon was significantly increased in the post-exercise by A-mix administration. These results suggest that pre-exercise ingestion of A-mix causes a shift of energy source from carbohydrate to fat combustion by increasing secretion of adrenalin and glucagon.

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.

Identification of a probiotic bacteria-derived activator of the aryl hydrocarbon receptor that inhibits colitis.

The aryl hydrocarbon receptor (AhR) recognizes environmental xenobiotics and is originally thought to be involved in the metabolism (detoxification) of the substances. Recently, AhR is highlighted as an important regulator of inflammation. Notably, accumulating evidence suggests that activation of the AhR suppresses inflammatory bowel diseases (IBDs). Therefore, non-toxic AhR activators become attractive drug candidates for IBD. This study identified 1,4-dihydroxy-2-naphthoic acid (DHNA), a precursor of menaquinone (vitamin K2) abundantly produced by Propionibacterium freudenreichii ET-3 isolated from Swiss-type cheese, as an AhR activator. DHNA activated the AhR pathway in human intestinal epithelial cell line Caco2 cells and in the mouse intestine. Oral treatment of mice with DHNA induced anti-microbial proteins RegIIIß and γ in the intestine, altered intestinal microbial flora and inhibited dextran sodium sulfate (DSS)-induced colitis, which recapitulated the phenotypes of AhR activation in the gut. As DHNA is commercially available in Japan as a prebiotic supplement without severe adverse effects, DHNA or its derivatives might become a promising drug candidate for IBD via AhR activation. The results also implicate that intestinal AhR might act not only as a sensor for xenobiotics in diet and water but also for commensal bacterial activity because DHNA is a precursor of vitamin K2 produced by vitamin K2-synthesizing commensal bacteria as well as propionic bacteria. Hence, DHNA might be a key bacterial metabolite in the host-microbe interaction to maintain intestinal microbial ecosystem.

Post-exercise impact of ingested whey protein hydrolysate on gene expression profiles in rat skeletal muscle: activation of extracellular signal-regulated kinase 1/2 and hypoxia-inducible factor-1α.

We have previously shown that whey protein hydrolysate (WPH) causes a greater increase in muscle protein synthesis than does a mixture of amino acids that is identical in amino acid composition. The present study was conducted to investigate the effect of WPH on gene expression. Male Sprague-Dawley rats subjected to a 2 h swimming exercise were administered either a carbohydrate-amino acid diet or a carbohydrate-WPH diet immediately after exercise. At 1 h after exercise, epitrochlearis muscle mRNA was sampled and subjected to DNA microarray analysis. We found that ingestion of WPH altered 189 genes after considering the false discovery rate. Among the up-regulated genes, eight Gene Ontology (GO) terms were enriched, which included key elements such as Cd24, Ccl2, Ccl7 and Cxcl1 involved in muscle repair after exercise. In contrast, nine GO terms were enriched in gene sets that were down-regulated by the ingestion of WPH, and these GO terms fell into two clusters, 'regulation of ATPase activity' and 'immune response'. Furthermore, we found that WPH activated two upstream proteins, extracellular signal-regulated kinase 1/2 (ERK1/2) and hypoxia-inducible factor-1α (HIF-1α), which might act as key factors for regulating gene expression. These results suggest that ingestion of WPH, compared with ingestion of a mixture of amino acids with an identical amino acid composition, induces greater changes in the post-exercise gene expression profile via activation of the proteins ERK1/2 and HIF-1α.

Prebiotic consumption in pregnant and lactating women increases IL-27 expression in human milk.

The consumption of probiotics by pregnant and lactating women may prevent the onset of allergic disorders in their children by increasing the concentrations of immunoactive agents such as cytokines in breast milk. Prebiotics such as fructo-oligosaccharides (FOS) increase the number of beneficial organisms such as bifidobacteria. Thus, prebiotics may have an effect similar to that of probiotics. The objective of the present study was to carry out a comprehensive analysis of mRNA expression in human milk cells to identify changes in the concentrations of cytokines in breast milk after the consumption of FOS (4 g × 2 times/d) by pregnant and lactating women. The microarray analysis of human milk cells demonstrated that the expression levels of five genes in colostrum samples and fourteen genes in 1-month breast milk samples differed more than 3-fold between the FOS and control groups (sucrose group). The mRNA expression level of IL-27, a cytokine associated with immunoregulatory function, was significantly higher in 1-month breast milk samples obtained from the FOS group than in those obtained from the control group. In addition, the protein concentrations of IL-27 in colostrum and 1-month breast milk samples were significantly higher in the FOS group than in the control group. In conclusion, the consumption of FOS by pregnant and lactating women increases the production of IL-27 in breast milk. Future studies will address the association of this phenomenon with the onset of allergic disorders in children.

On the Moisture Absorption Capability of Ionic Liquids.

Due to their many attractive physicochemical properties, ionic liquids (ILs) have received extensive attention with numerous applications proposed in various fields of science and technology. Despite this, the molecular origins of many of their properties, such as the moisture absorption capability, are still not well understood. For insight into this, we systematically synthesized 24 types of ILs by the combination of the dimethyl phosphate anion with various types of alkyl group-substituted cyclic cations─imidazolium, pyrazolium, 1,2,3-triazolium, and 1,2,4-triazolium cations─and performed a detailed analysis of the dehumidification properties of these ILs and their aqueous solutions. It was found that these IL systems have a high dehumidification capability (DC). Among the monocationic ILs, the best performance was obtained with 1-cyclohexylmethyl-4-methyl-1,2,4-triazolium dimethyl phosphate, whose DC (per mol) value is 14 times higher than that of popular solid desiccants like CaCl2 and silica gel. Dicationic ILs, such as 1,1'-(propane-1,3-diyl)bis(4-methyl-1,2,4-triazolium) bis(dimethyl phosphate), showed an even better moisture absorption, with a DC (per mol) value about 20 times higher than that of CaCl2. Small- and wide-angle X-ray scattering measurements of eight types of 1,2,4-triazolium dimethyl phosphate ILs were performed and revealed that the majority of these ILs form nanostructures. Such nanostructures, which vary with the identity of the IL and the water content, fall into three main categories: bicontinuous microemulsions, hexagonal cylinders, and micelle-like structures. Water in the solutions exists primarily in polar regions in the nanostructures; these spaces function as water pockets at relatively low water concentrations. Since the structure and stability of the aggregated forms of the ILs are mainly governed by the interactions of nonpolar groups, the alkyl side chains of the cations play an important role in the DC and temperature-dependent equilibrium water vapor pressure of the IL solutions. Our experimental findings and molecular dynamics simulation results shed light on the moisture absorption mechanism of the IL aqueous solutions from a molecular perspective.

Advanced application of bovine intestinal epithelial cell line for evaluating regulatory effect of lactobacilli against heat-killed enterotoxigenic Escherichia 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 pathogen-associated 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-1α and MCP-1 in BIE cells by activating both NF-κB 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-κB 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.

Strain-specific identification of Bifidobacterium bifidum OLB6378 by PCR.

The aim of the present study was to develop a strain-specific polymerase chain reaction (PCR) primer set for the detection of Bifidobacterium bifidum OLB6378 (OLB6378) that can serve as suitable probiotics for infants. The random amplified polymorphic DNA (RAPD)-PCR technique was used to obtain OLB6378-specific PCR products. One OLB6378-specific RAPD-PCR product was obtained after testing 97 RAPD primers, and was sequenced. Thirteen PCR primer sets were designed from the sequence. One PCR primer set was found to amplify one PCR product when genomic DNA of OLB6378 was used as template. The primer set did not amplify any PCR product when the other genomic DNA was used as template. The primer set was tested with 47 strains of B. bifidum and 20 strains of the other Bifidobacterium species. As a result, we developed an OLB6378-specific primer set, one that should be useful not only for the detection of OLB6378 but also for the quantification of OLB6378.

Oral administration of Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1 suppresses inflammation by decreasing interleukin-6 responses in a murine model of atopic dermatitis.

The oral intake of Lactobacillus spp. can provide beneficial effects to the host by modulating the immune response. Atopic dermatitis (AD) is an allergic inflammatory disease mediated by various immune responses. In this study, we examined the effect of a Lactobacillus strain, Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 (OLL1073R-1), on AD development in a murine model of AD that was developed by the topical application of mite antigen in NC/Nga mice. The oral intake of heat-killed OLL1073R-1 cells inhibited both the development of dermatitis and the elevation of an acute inflammation marker, serum amyloid A. Another bacterial strain, Lactobacillus rhamnosus OLL2984, exerted no inhibitory effects on dermatitis. The oral intake of heat-killed OLL1073R-1 cells also attenuated secretion of IL-6 from lymph node cells in response to mite antigen and reduced IL-6 levels in inflamed tissues, such as auricles. Production of IFN-γ or IL-4 was not influenced by OLL1073R-1 intake. We also found that inhibition of IL-6 signaling by gp130-Fc (a fusion protein consisting of the extracellular portion of glycoprotein 130 fused to the Fc region of human IgG1) markedly decreased the severity of dermatitis in NC/Nga mice. Moreover, secretion of IL-6 by lymph node cells was augmented in NC/Nga mice compared with that in BALB/c mice. These results indicate that IL-6 plays an essential role in the development of dermatitis in the NC/Nga mouse model of AD, and that OLL1073R-1 inhibits dermatitis, at least in part, by suppressing the IL-6 response.

Efficacy of 1-kestose supplementation in patients with mild to moderate ulcerative colitis: A randomised, double-blind, placebo-controlled pilot study.

BACKGROUND: Ulcerative colitis involves an excessive immune response to intestinal bacteria. Whether administering prebiotic 1-kestose is effective for active ulcerative colitis remains controversial. AIMS: This randomised, double-blind, placebo-controlled pilot trial investigated the efficacy of 1-kestose against active ulcerative colitis. METHODS: Forty patients with mild to moderate active ulcerative colitis were randomly treated with 1-kestose (N = 20) or placebo (maltose, N = 20) orally for 8 weeks in addition to the standard treatment. The Lichtiger clinical activity index and Ulcerative Colitis Endoscopic Index of Severity were determined. Faecal samples were analysed to evaluate the gut microbiome and metabolites. RESULTS: The clinical activity index at week 8 was significantly lower in the 1-kestose group than in the placebo group (3.8 ± 2.7 vs. 5.6 ± 2.1, p = 0.026). Clinical remission and response rates were higher in the 1-kestose group than in the placebo group (remission: 55% vs. 20%, p = 0.048; response: 60% vs. 25%, p = 0.054). The Ulcerative Colitis Endoscopic Index of Severity at week 8 was not significantly different (2.8 ± 1.6 vs. 3.5 ± 1.6, p = 0.145). Faecal analysis showed significantly reduced alpha-diversity in the 1-kestose group, with a decreased relative abundance of several bacteria, including Ruminococcus gnavus group. The short-chain fatty acid levels were not significantly different between the groups. The incidence of adverse events was comparable between the groups. DISCUSSION: Oral 1-kestose is well tolerated and provides clinical improvement for patients with mild to moderate ulcerative colitis through modulation of the gut microbiome.

Monoclonal Antibody Against Mature Interleukin-18 Ameliorates Colitis in Mice and Improves Epithelial Barrier Function.

BACKGROUND: Antitumor necrosis factor (TNF)-α antibodies have improved the outcome of inflammatory bowel disease (IBD); but half of patients remain unresponsive to treatment. Interleukin-18 (IL-18) gene polymorphism is associated with resistance to anti-TNF-α antibodies, but therapies targeting IL-18 have not been clinically applied. Only the mature protein is biologically active, and we aimed to investigate whether specific inhibition of mature IL-18 using a monoclonal antibody (mAb) against a neoepitope of caspase-cleaved mature IL-18 could be an innovative treatment for IBD. METHODS: The expression of precursor and mature IL-18 in patients with UC was examined. Colitis was induced in C57/BL6 mice by administering dextran sulfate sodium (DSS), followed by injection with anti-IL-18 neoepitope mAb. Colon tissues were collected and subjected to histological analysis, immunohistochemistry, immunoblotting, and quantitative polymerase chain reaction. Colon epithelial permeability and microbiota composition were analyzed. RESULTS: Mature IL-18 expression was elevated in colon tissues of patients with active ulcerative colitis. Administration of anti-IL-18 neoepitope mAb ameliorated acute and chronic DSS-induced colitis; reduced interferon-γ, TNF-α, and chemokine (CXC motif) ligand-2 production and epithelial cell permeability; promoted goblet cell function; and altered the intestinal microbiome composition. The suppressive effect of anti-IL-18 neoepitope mAb was superior to that of anti-whole IL-18 mAb. Furthermore, combination therapy with anti-TNF-α Ab suppressed acute and chronic colitis additively by suppressing cytokine expressions and reducing cell permeability by upregulating claudin1 and occludin expression. CONCLUSIONS: Anti-IL-18 neoepitope mAb ameliorates acute and chronic colitis, suggesting that this mAb will be an innovative therapeutic option for IBD.

We investigate a novel monoclonal antibody that specifically recognizes a neoepitope of caspase-cleaved IL-18 and alleviates dextran sulfate sodium-induced colitis by suppressing the secretion of inflammatory cytokines, improving intestinal epithelial permeability, promoting goblet cell function, and regulating intestinal microbiota.

Immunobiotic Lactobacillus jensenii elicits anti-inflammatory activity in porcine intestinal epithelial cells by modulating negative regulators of the Toll-like receptor signaling pathway.

The effect of Lactobacillus jensenii TL2937 on the inflammatory immune response triggered by enterotoxigenic Escherichia coli (ETEC) and lipopolysaccharide (LPS) in a porcine intestinal epitheliocyte cell line (PIE cells) was evaluated. Challenges with ETEC or LPS elicited Toll-like receptor 4 (TLR4)-mediated inflammatory responses in cultured PIE cells, indicating that our cell line may be useful for studying inflammation in the guts of weaning piglets. In addition, we demonstrated that L. jensenii TL2937 attenuated the expression of proinflammatory cytokines and chemokines caused by ETEC or LPS challenge by downregulating TLR4-dependent nuclear factorκB (NF-κB) and mitogen-activated protein kinase (MAPK) activation. Furthermore, we demonstrated that L. jensenii TL2937 stimulation of PIE cells upregulated three negative regulators of TLRs: A20, Bcl-3, and MKP-1, deepening the understanding of an immunobiotic mechanism of action. L. jensenii TL2937-mediated induction of negative regulators of TLRs would have a substantial physiological impact on homeostasis in PIE cells, because excessive TLR inflammatory signaling would be downregulated. These results indicated that PIE cells can be used to study the mechanisms involved in the protective activity of immunobiotics against intestinal inflammatory damage and may provide useful information for the development of new immunologically functional feeds that help to prevent inflammatory intestinal disorders, including weaning-associated intestinal inflammation.

Gelsolin as a Potential Biomarker for Endoscopic Activity and Mucosal Healing in Ulcerative Colitis.

The therapeutic goal in ulcerative colitis is mucosal healing, which requires improved non-invasive biomarkers to evaluate disease activity. Gelsolin is associated with several autoimmune diseases, and here, we aimed to analyze its usefulness as a serological biomarker for clinical and endoscopic activities in ulcerative colitis. Patients with ulcerative colitis (n = 138) who had undergone blood tests and colonoscopy were included. Serum gelsolin was measured using enzyme-linked immunosorbent assay, and correlation between the gelsolin level and clinical and endoscopic activities was examined. The serum gelsolin level in patients with ulcerative colitis was significantly lower than that in healthy subjects, and it decreased in proportion to increasing Mayo score and Mayo endoscopic subscore. The area under the curve for correlation between clinical and endoscopic remission and serum gelsolin level was higher than that for C-reactive protein. Furthermore, in C-reactive protein-negative patients, the serum gelsolin level was lower in the active phase than in remission. Our findings indicate that the serum gelsolin level correlates with clinical and endoscopic activities in ulcerative colitis, has a higher sensitivity and specificity than C-reactive protein, and can detect mucosal healing, suggesting that gelsolin can be used as a biomarker for ulcerative colitis.

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.

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(+)CD11R1(high) 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.

Suppression of oral tolerance by Lactococcus lactis in mice.

Although oral ovabumin (OVA) administration suppressed the antibody (Ab) response in OVA-immunized mice, Lactococcus lactis increased OVA-specific IgG2a in these mice. L. lactis increased the casein-specific IgG level in NC/Nga mice fed on a casein diet. The percentage of CD4(+)CD25(+) cells was increased in DO11.10 mice orally given OVA, but this increase of CD4(+)CD25(+) cells were suppressed in L. lactis-fed DO11.10 mice.

Reducing the risk of infection in the elderly by dietary intake of yoghurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1.

Immune senescence potentially leads to an increased risk of infections. It is desirable to augment the immune system and protect against infections by daily consumption of immunostimulatory food. The present study evaluated whether the intake of yoghurt fermented with Lactobacillus delbrueckii ssp. bulgaricus (L. bulgaricus) OLL1073R-1 has an effect on resistance to the common cold. We conducted two independent studies, in which fifty-seven (median age 74.5 years) and eighty-five healthy elderly individuals (median age 67.7 years) were participants. In each study, the subjects were divided into two groups based on age and sex and instructed to eat 90 g yoghurt or drink 100 ml milk once per d over an 8- or 12-week period. A meta-analysis of the results of these two independent studies showed the risk of catching the common cold was about 2.6 times lower (OR 0.39; P = 0.019) in the yoghurt group than in the milk group and the increase of natural killer cell activity was significantly higher in the yoghurt group than in the milk group (P = 0.028). In addition, the quality of life score for the 'eye/nose/throat' system after intake was significantly higher in the yoghurt group than in the milk group and the improvement of the score was correlated with the promotion of natural killer cell activity. In conclusion, consumption of yoghurt fermented with L. bulgaricus OLL1073R-1 augmented natural killer cell activity and reduced the risk of catching the common cold in elderly individuals.

Efficacy of oral administration of a heat-killed Lactobacillus gasseri OLL2809 on patients of Japanese cedar pollinosis with high Japanese-cedar pollen-specific IgE.

A randomized, double-blind, placebo-controlled clinical trial was conducted to determine whether oral administration of heat-killed Lactobacillus gasseri OLL2809 would affect the immune response and reduce the symptoms of Japanese cedar pollinosis (JCP) in subjects with JCP. Following a 1-week pre-observation period, the subjects were randomly divided into two groups and were orally administered a placebo or tablets containing 100 mg of L. gasseri OLL2809 per d for 8 weeks during the pollen season in 2007. The results showed no obvious differences between the groups. Supplementary subgroup analysis revealed that the OLL2809 subgroups with CAP-RAST scores of 4 or 5 exhibited improvement in nasal symptoms scores and serum allergy-related items, including Japanese cedar pollen-specific IgE levels. L. gasseri OLL2809 was found to be effective in reducing symptoms in subjects with a high predisposition to allergies by modulating systemic immune systems.

Effects of Whey Protein Hydrolysate Ingestion on Postprandial Aminoacidemia Compared with a Free Amino Acid Mixture in Young Men.

To stimulate muscle protein synthesis, it is important to increase the plasma levels of essential amino acids (EAA), especially leucine, by ingesting proteins. Protein hydrolysate ingestion can induce postprandial hyperaminoacidemia; however, it is unclear whether protein hydrolysate is associated with higher levels of aminoacidemia compared with a free amino acid mixture when both are ingested orally. We assessed the effects of whey protein hydrolysate (WPH) ingestion on postprandial aminoacidemia, especially plasma leucine levels, compared to ingestion of a free amino acid mixture. This study was an open-label, randomized, 4 × 4 Latin square design. After 12⁻15 h of fasting, 11 healthy young men ingested the WPH (3.3, 5.0, or 7.5 g of protein) or the EAA mixture (2.5 g). Blood samples were collected before ingestion and at time points from 10 to 120 min after ingestion, and amino acids, insulin, glucose and insulin-like growth factor-1 (IGF-1) concentrations in plasma were measured. Even though the EAA mixture and 5.0 g of the WPH contained similar amounts of EAA and leucine, the WPH was associated with significantly higher plasma EAA and leucine levels. These results suggest that the WPH can induce a higher level of aminoacidemia compared with a free amino acid mixture when both are ingested orally.