Lactobacillus helveticus SBT2171 Alleviates Perennial Allergic Rhinitis in Japanese Adults by Suppressing Eosinophils: A Randomized, Double-Blind, Placebo-Controlled Study.

This article examines the effects of fermented milk (FM) containing Lactobacillus helveticus SBT2171 (LH2171) on the subjective symptoms of individuals with mild and moderate perennial allergy. Two hundred subjects were divided into two groups and consumed FM containing LH2171 or placebo FM once per day for 16 weeks. The primary endpoints were defined as per the degree of nasal and ocular symptoms and difficulty in daily life as determined by the Japanese guidelines for allergy rhinitis and the Japanese allergic rhinitis standard quality of life questionnaire, respectively. The secondary endpoints included parameters related to allergic symptoms in the blood and nasal fluids, as well as the mental status. The severity of allergic rhinitis significantly improved in the LH2171 group compared to that in the placebo group. Additionally, the LH2171 group showed a significantly lower degree of "stuffy nose" (as per the diary survey) than the placebo group. Eosinophil counts in the nasal fluids and in the blood were significantly lower in the LH2171 group compared to the placebo group. Thus, the oral administration of FM containing LH2171 cells alleviated perennial allergic rhinitis in individuals with mild and moderate symptoms, possibly via suppression of eosinophils in both the blood and nasal fluids.

Lactobacillus helveticus SBT2171 alleviates allergic symptoms in a murine model for pollen allergy.

Lactic acid bacteria are known to have various health-promoting effects and are highly expected to find applications in anti-allergic food materials. In this study, we focused on Lactobacillus helveticus SBT2171 (LH2171), which reportedly modifies some unique immune responses and ameliorated symptoms of patients allergic to mites and house dust in the previous studies. We examined the effect of LH2171 on cytokine production by antigen-stimulated murine naïve splenocytes in vitro and demonstrated that it inhibited IL-4 and IL-13 production while enhancing IFN-γ and IL-10 production. Then, we examined the anti-allergic effect of LH2171 in vivo using a murine model of pollen allergy and found that LH2171 reduced the sneezing frequency when orally administered to mice. We successfully confirmed the immune modulatory activity of LH2171 and its anti-allergic activity against inhaled antigens. These evidences would contribute to identifying the anti-allergic mechanism of LH2171.Abbreviations: ALDH: aldehyde dehydrogenase; EGCG: epigallocatechin gallate; LAB: lactic acid bacteria; LH2171: Lactobacillus helveticus SBT2171; NALT: nasal-associated lymphoid tissue; OVA: ovalbumin.

Preventive Effect of Lactobacillus helveticus SBT2171 on Collagen-Induced Arthritis in Mice.

We recently reported that the intraperitoneal inoculation of Lactobacillus helveticus SBT2171 inhibited the development of collagen-induced arthritis (CIA), a murine model of rheumatoid arthritis (RA). In the present study, we evaluated the effect of the oral administration of L. helveticus SBT2171 on CIA development and on the regulation of antigen-specific antibody production and inflammatory immune cells, which have been implicated in the development of RA. Both oral administration and intraperitoneal inoculation of L. helveticus SBT2171 reduced joint swelling, body weight loss, and the serum level of bovine type II collagen (CII)-specific antibodies in the CIA mouse model. The intraperitoneal inoculation also decreased the arthritis incidence, joint damage, and serum level of interleukin (IL)-6. In addition, the numbers of total immune cells, total B cells, germinal center B cells, and CD4+ T cells in the draining lymph nodes were decreased following intraperitoneal inoculation of L. helveticus SBT2171. These findings demonstrate the ability of L. helveticus SBT2171 to downregulate the abundance of immune cells and the subsequent production of CII-specific antibodies and IL-6, thereby suppressing the CIA symptoms, indicating its potential for use in the prevention of RA.

Lactobacillus helveticus SBT2171 Attenuates Experimental Autoimmune Encephalomyelitis in Mice.

We recently reported that Lactobacillus helveticus SBT2171 (LH2171) inhibited the proliferation and inflammatory cytokine production of primary immune cells in vitro, and alleviated collagen-induced arthritis (CIA) in mice, a model of human rheumatoid arthritis (RA). In this study, we newly investigated whether LH2171 could relieve the severity of experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS), which is an autoimmune disease, but develop the symptoms by different mechanisms from RA. In MS and EAE, main cause of the disease is the abnormality in CD4+ T cell immunity, whereas in RA and CIA, is that in antibody-mediated immunity. The intraperitoneal administration of LH2171 significantly decreased the incidence and clinical score of EAE in mice. LH2171 also reduced the numbers of pathogenic immune cells, especially Th17 cells, in the spinal cord at the peak stage of disease severity. Interestingly, before the onset of EAE, LH2171 administration remarkably decreased the ratio of Th17 cells to CD4+ T cells in the inguinal lymph nodes (LNs), where pathogenic immune cells are activated to infiltrate the central nervous system, including the spinal cord. Furthermore, the expression of interleukin (IL)-6, an inflammatory cytokine essential for Th17 differentiation, decreased in the LNs of LH2171-administered mice. Moreover, LH2171 significantly inhibited IL-6 production in vitro from both DC2.4 and RAW264.7 cells, model cell lines of antigen-presenting cells. These findings suggest that LH2171 might down-regulate IL-6 production and the subsequent Th17 differentiation and spinal cord infiltration, consequently alleviating EAE symptoms.

Lactobacillus helveticus SBT2171 inhibits lymphocyte proliferation by regulation of the JNK signaling pathway.

Lactobacillus helveticus SBT2171 (LH2171) is a lactic acid bacterium with high protease activity and used in starter cultures in the manufacture of cheese. We recently reported that consumption of cheese manufactured using LH2171 alleviated symptoms of dextran sodium sulfate (DSS)-induced colitis in mice. In this study, we have examined whether LH2171 itself exerts an inhibitory effect on the excessive proliferation of lymphocytes. We found that LH2171 inhibited the proliferation of LPS-stimulated mouse T and B cells, and the human lymphoma cell lines, Jurkat and BJAB. Cell cycle analysis showed an accumulation of LH2171-treated BJAB cells in the G2/M phase. Further, phosphorylation of c-Jun N-terminal kinase (JNK) and c-Jun was reduced by LH2171 in BJAB cells. Subsequently, expression of cell division cycle 2 (CDC2), regulated by the JNK signaling pathway and essential for G2/M phase progression, was inhibited by LH2171. It was also demonstrated that intraperitoneal administration of LH2171 strongly alleviated symptoms of collagen-induced arthritis (CIA) in mice. These findings suggest that LH2171 inhibits the proliferation of lymphocytes through a suppression of the JNK signaling pathway and exerts an immunosuppressive effect in vivo.

Lymphatic absorption of choline plasmalogen is much higher than that of ethanolamine plasmalogen in rats.

BACKGROUND: Plasmalogen is a subclass of phospholipids widely distributed in animal tissues and ingested as food; however, the absorptive characteristics of different classes of plasmalogen have not been clarified. AIM OF STUDY: Our object was to compare the lymphatic output of choline and ethanolamine plasmalogens after an administration of phospholipid preparations containing each class of plasmalogens, and to analyze molecular species of plasmalogen absorbed into the lymph. METHODS: A duodenal infusion of 1 ml of 10% emulsion of choline phospholipid (PC) containing 50.6% choline plasmalogen (PlsCho) or ethanolamine phospholipid (PE) containing 52.5% ethanolamine plasmalogen (PlsEtn) was administered in the lymph duct-cannulated rats. Molecular species of plasmalogen absorbed into the lymph were measured by LC-MS/MS. RESULTS: Lymph outputs of PlsCho and PlsEtn increased and reached a peak value at 3 h after PC and PE injection, respectively. The peak value of PlsCho was much higher and remained at a high level until 8 h, whereas PlsEtn output fell to half of the peak value at 7 h. Total lymphatic output of PlsCho was 5-times higher than that of PlsEtn. Compositions of sn-1 in lymph plasmalogens roughly reflected those of the injected lipids, whereas sn-2 in both PlsCho and PlsEtn was rich in arachidonic acid (20:4) regardless of the composition of the administered fatty acid. Both plasmalogen and lysoplasmalogen after PE injection were not released into the portal vein. CONCLUSION: Lymphatic absorption of PlsCho is much higher than that of PlsEtn in rats, and plasmalogens are re-esterified as 20:4-rich forms in the small intestine.