Lactobacillus paragasseri SBT2055 Activates Plasmacytoid Dendritic Cells and Improves Subjective Symptoms of Common Cold in Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled Parallel-Group Comparative Trial.

This study investigated whether Lactobacillus paragasseri SBT2055 (LG2055) activates plasmacytoid dendritic cells (pDCs) and suppresses common cold symptoms in healthy adults. Cell-based experiments showed that a LG2055 treatment upregulated CD86 and HLA-DR expression in pDCs, indicating that LG2055 activates pDCs in vitro. In a subsequent randomized, double-blind, placebo-controlled, parallel-group comparative trial, 200 participants were randomly divided into two groups and consumed three capsules with or without LG2055 once daily for 12 weeks. The primary outcome was the score on a daily physical health questionnaire survey of common cold symptoms. Three participants discontinued the trial and six participants were excluded from the analysis, thus 191 participants (95 in the LG2055 group and 96 in the placebo group) were analyzed. The LG2055 group showed a significantly higher ratio of "without symptoms" responses for runny nose, plugged nose, sneezing, sore throat, hoarseness, and chill than the placebo group. Furthermore, a stratified analysis revealed that LG2055 intake enhanced CD86 and HLA-DR expression in the pDCs of the participants with low secretion rates of salivary secretory immunoglobulin A. These data suggest that LG2055 suppresses the subjective symptoms of the common cold by activating pDCs and improving the host's immune system in healthy adults, especially in immune-weakened individuals (UMIN000049183).

Intake of Lactobacillus paragasseri SBT2055 improves subjective symptoms of common cold during winter season in healthy adults: A randomized, double-blind, placebo-controlled parallel-group comparative study.

Objective: Lactobacillus paragasseri SBT2055 (LG2055) has been reported to show immunostimulating effects. This study aimed to investigate the effects of LG2055 on the subjective symptoms of the physical condition in healthy adults. Materials and methods: In this randomized, double-blind, placebo-controlled, parallel-group comparative study, Japanese individuals aged 20-64 years were recruited. A total of 200 participants were randomly divided into two groups by an independent controller (LG2055 and placebo groups; 100 participants per group). Drinkable yogurts containing LG2055 or lacking LG2055 (placebo) were used as test samples. The participants ingested one bottle of the test sample once a day for 12 weeks. A daily physical health questionnaire survey (about common cold symptoms) was performed as the primary outcome, and immunological and oxidative stress markers in saliva and serum were evaluated as secondary outcomes. Results: In total, 198 participants completed the scheduled intake of the test samples, and five participants were excluded from the final analysis. Consequently, 193 participants (LG2055 group, n = 97; placebo group, n = 96) in the Per-Protocol Set were included in the efficacy analysis. The cumulative days of each symptom were evaluated, and the LG2055 group showed a significantly higher ratio of "without symptom" in runny nose, plugged nose, sneezing, sore throat, hoarseness, cough, headache, feeling tired, and fever than the placebo group, indicating that the incidence rates of common cold symptoms were lower in the LG2055 group. Additionally, changes in the salivary secretory IgA levels were significantly higher, and the serum derivatives of reactive oxygen metabolites levels were significantly lower in the LG2055 group. Conclusion: Our study revealed that intake of LG2055 decreased common cold symptoms and improved immune parameters in healthy adults. This suggests that LG2055 contributes to the maintenance of physical conditions by improving the host immune system. Clinical trial registration: [https://www.umin.ac.jp/ctr/index.htm], identifier [UMIN000045901].

S-Layer Protein of Lactobacillus helveticus SBT2171 Promotes Human ß-Defensin 2 Expression via TLR2-JNK Signaling.

Antimicrobial peptides that contribute to innate immunity are among the most important protective measures against infection in many organisms. Several substances are known to regulate the expression of antimicrobial peptides. In this study, we investigated the factors in lactic acid bacteria (LAB) that induce antimicrobial peptide expression in the host. We found that Lactobacillus helveticus SBT2171 (LH2171) induced the expression of human ß-defensin (hBD)2 in Caco-2 human colonic epithelial cells. Specifically, surface layer protein (SLP) of LH2171 stimulated hBD2 expression by activating c-Jun N-terminal kinase (JNK) signaling via Toll-like receptor (TLR)2 in Caco-2 cells. SLPs extracted from other lactobacilli similarly increased hBD2 expression, suggesting that this stimulatory effect is common feature of Lactobacillus SLPs. Interestingly, Lactobacillus strains that strongly induced hBD2 expression also potently activated JNK signaling. Thus, upregulation of hBD2 induced by TLR2-JNK signaling contributes to protection of the host against infection.

Lactobacillus helveticus SBT2171 upregulates the expression of ß-defensin and ameliorates periodontal disease caused by Porphyromonas gingivalis.

Antimicrobial peptides play important roles in the innate immune system of various organisms, and they may also be considered to prevent the organisms from infections. In particular, ß-defensins, mainly produced in epithelial cells, are recognized as one of the major antimicrobial peptides in mammals, including humans. In this study, we showed that Lactobacillus helveticus SBT2171 (LH2171), one of the several species of lactic acid bacteria, upregulates the production of ß-defensins in oral epithelial cells in vitro. Moreover, LH2171 reduced the increase of proinflammatory cytokine expression, induced by Porphyromonas gingivalis stimulation, in gingival epithelial cells. These data suggested that LH2171 suppresses P. gingivalis-induced inflammation by upregulating the expression of ß-defensins in gingival epithelial cells. We subsequently investigated the effects of LH2171 in vivo and revealed that ß-defensin expression was increased in the oral cavities of LH2171-fed mice. Furthermore, LH2171 decreased alveolar bone loss, gingival inflammation, and amounts of P. gingivalis-specific 16S ribosomal RNA in the gingiva of P. gingivalis-inoculated mice. Taken together, our results showed that LH2171 upregulates the expression of ß-defensins in oral cavity, thereby decreasing the number of P. gingivalis consequently ameliorating the experimental periodontal disease.

Protective effects and functional mechanisms of Lactobacillus gasseri SBT2055 against oxidative stress.

Lactobacillus gasseri SBT2055 (LG2055) is one of the probiotic lactic acid bacteria. Recently, we demonstrated that feeding with LG2055 extended the lifespan of Caenorhabditis elegans and that the prolongevity effect was dependent upon the regulation of oxidative stress response. In this study, we assessed whether LG2055 regulated the oxidative stress response of mammalian cells. In NIH-3T3 cells and primary mouse embryonic fibroblast cells, low cell proliferation rates and high reactive oxygen species levels were observed following paraquat treatment. LG2055 treatment suppressed these responses in paraquat-treated cells, indicating that LG2055 protected against oxidative stress in mammalian cells. The mRNA expression of oxidative stress-related genes, total nuclear factor-erythroid-2-related factor 2 (Nrf2) protein levels, and the nuclear translocation of Nrf2 were increased by LG2055 treatment. These results suggested that the Nrf2-antioxidant response element (ARE) signaling pathway was activated by LG2055. Furthermore, c-Jun NH2-terminal kinase (JNK) was activated by LG2055 treatment and the inhibition of JNK suppressed the activation of the Nrf2-ARE signaling pathway in LG2055-treated cells. Together, these findings suggest that LG2055 activated the Nrf2-ARE signaling pathway by JNK activation, thus strengthening the defense system against oxidative stress in mammalian cells.

Effects and mechanisms of prolongevity induced by Lactobacillus gasseri SBT2055 in Caenorhabditis elegans.

Lactic-acid bacteria are widely recognized beneficial host associated groups of the microbiota of humans and animals. Some lactic-acid bacteria have the ability to extend the lifespan of the model animals. The mechanisms behind the probiotic effects of bacteria are not entirely understood. Recently, we reported the benefit effects of Lactobacillus gasseriSBT2055 (LG2055) on animal and human health, such as preventing influenza A virus, and augmentation of IgA production. Therefore, it was preconceived that LG2055 has the beneficial effects on longevity and/or aging. We examined the effects of LG2055 on lifespan and aging of Caenorhabditis elegans and analyzed the mechanism of prolongevity. Our results demonstrated that LG2055 has the beneficial effects on longevity and anti-aging of C. elegans. Feeding with LG2055 upregulated the expression of the skn-1 gene and the target genes of SKN-1, encoding the antioxidant proteins enhancing antioxidant defense responses. We found that feeding with LG2055 directly activated SKN-1 activity via p38 MAPK pathway signaling. The oxidative stress response is elicited by mitochondrial dysfunction in aging, and we examined the influence of LG2055 feeding on the membrane potential of mitochondria. Here, the amounts of mitochondria were significantly increased by LG2055 feeding in comparison with the control. Our result suggests that feeding with LG2055 is effective to the extend lifespan in C. elegans by a strengthening of the resistance to oxidative stress and by stimulating the innate immune response signaling including p38MAPK signaling pathway and others.

A method for the rapid discovery of naturally occurring products by proteins immobilized on magnetic beads and reverse affinity chromatography.

A highly efficient screening method for naturally occurring products that bind to a specific target protein was demonstrated by using hVDR magnetic beads. The native ligand 1alpha,25(OH)2 VD3 (1) was selectively bound by hVDR magnetic beads when present in a mixture of natural compounds. Furthermore, this method was shown to be applicable to the identification of natural products that interact with a specific protein immobilized on the beads from an extract of a natural resource. Two new natural compounds were isolated by this method. This approach will be helpful for the discovery of novel, naturally occurring products that bind to specific target proteins. This method has the further advantages that it can identify the HPLC peak corresponding to the target compound for isolation, as well as provide important UV, CD, or MS profile information.