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Modulation of T Regulatory and Dendritic Cell Phenotypes Following Ingestion of Bifidobacterium longum, AHCC® and Azithromycin in Healthy Individuals.
Chowdhury, AH, Cámara, M, Verma, C, Eremin, O, Kulkarni, AD, Lobo, DN
Nutrients. 2019;(10)
Abstract
The probiotic Bifidus BB536 (BB536), which contains Bifidobacterium longum, has been shown to have enhanced probiotic effects when given together with a standardized extract of cultured Lentinula edodes mycelia (AHCC®, Amino Up Co. Ltd., Sapporo, Japan). BB536 and AHCC® may modulate T cell and dendritic cell (DC) phenotypes, and cytokine profiles to favour anti-inflammatory responses following antibiotic ingestion. We tested the hypothesis that orally administered BB536 and/or AHCC®, results in modulation of immune effector cells with polarisation towards anti-inflammatory responses following antibiotic usage. Forty healthy male volunteers divided into 4 equal groups were randomised to receive either placebo, BB536, AHCC® or a combination for 12 days in a double-blind manner. After 7 days volunteers also received 250 mg azithromycin for 5 days. Cytokine profiles from purified CD3+ T cells stimulated with PDB-ionomycin were assessed. CD4+ CD25+ forkhead box P3 (Foxp3) expression and peripheral blood DC subsets were assessed prior to treatment and subsequently at 7 and 13 days. There was no difference in cytokine secretion from stimulated CD3+ T cells between treatment groups. Compared with baseline, Foxp3 expression (0.45 ± 0.1 vs. 1.3 ± 0.4; p = 0.002) and interferon-gamma/interleukin-4 (IFN-γ/IL-4) ratios were increased post-treatment in volunteers receiving BB536 (p = 0.031), although differences between groups were not significant. For volunteers receiving combination BB536 and AHCC®, there was an increase in myeloid dendritic cells (mDC) compared with plasmacytoid DC (pDC) counts (80% vs. 61%; p = 0.006) at post treatment time points. mDC2 phenotypes were more prevalent, compared with baseline, following combination treatment (0.16% vs. 0.05%; p = 0.002). Oral intake of AHCC® and BB536 may modulate T regulatory and DC phenotypes to favour anti-inflammatory responses following antibiotic usage.
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Lactobacillus reuteri supplements do not affect salivary IgA or cytokine levels in healthy subjects: A randomized, double-blind, placebo-controlled, cross-over trial.
Jørgensen, MR, Keller, MK, Kragelund, C, Hamberg, K, Ericson, D, Nielsen, CH, Twetman, S
Acta odontologica Scandinavica. 2016;(5):399-404
Abstract
OBJECTIVES To evaluate the effect of daily ingestion of probiotic lactobacilli on the levels of secretory IgA (sIgA) and selected cytokines in whole saliva of healthy young adults. MATERIALS AND METHODS The study group consisted of 47 healthy adults (18-32 years) who volunteered for a randomized, double-blind, placebo-controlled, cross-over trial after informed consent. During intervention, the subjects ingested two lozenges per day containing two strains of the probiotic bacterium Lactobacillus reuteri (DSM 17938 and ATCC PTA 5289) or placebo lozenges. The intervention and wash-out periods were 3 weeks. Saliva samples were collected at baseline, immediately after each intervention period and 3 weeks post-intervention. ELISA was used to measure sIgA and luminex technology was used to measure the interleukins (IL)-1β, IL-6, IL-8 and IL-10. For statistical analyses a mixed ANOVA model was employed to calculate changes in the salivary outcome variables. RESULTS Forty-one subjects completed the study and reported a good compliance. No significant differences in the concentrations of salivary sIgA or cytokines were recorded between the L. reuteri and placebo interventions or between baseline and 3 weeks post-intervention levels. No side- or adverse effects were reported. CONCLUSIONS Supplementation with two strains of the probiotic L. reuteri did not affect sIgA or cytokine levels in whole saliva in healthy young adults. The results thereby indicate that daily oral supplementation with L. reuteri do not seem to modulate the salivary oral immune response in healthy young subjects (ClinicalTrials.gov NCT02017886).
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Daily Intake of Heat-killed Lactobacillus plantarum L-137 Decreases the Probing Depth in Patients Undergoing Supportive Periodontal Therapy.
Iwasaki, K, Maeda, K, Hidaka, K, Nemoto, K, Hirose, Y, Deguchi, S
Oral health & preventive dentistry. 2016;(3):207-14
Abstract
PURPOSE Heat-killed Lactobacillus plantarum L-137 (HK L-137) has been shown to activate innate and acquired immunity in humans. The aim of this randomised, double-blind, placebo-controlled clinical trial was to examine the effects of the oral administration of HK L-137 on the outcome of periodontal therapy. MATERIALS AND METHODS Thirty-nine patients undergoing supportive periodontal therapy (SPT) were randomly assigned to receive a capsule containing 10 mg of HK L-137 or a placebo capsule daily for 12 weeks. Nineteen patients in the experimental group and 17 patients in the control group were followed-up. Clinical parameters, including plaque index (PI), gingival index (GI), bleeding on probing (BOP), and probing depth (PD) were scored at baseline and weeks 4, 8 and 12 prior to prophylaxis in conjunction with regular SPT visits. RESULTS BOP and the number of teeth or sites with PD ≥ 4 mm were significantly reduced in both groups by a successive SPT programme, while there was significantly greater PD reduction (p < 0.05) at teeth with site(s) with PD ≥ 4 mm at baseline in the experimental group than in the control group at week 12. CONCLUSION These clinical findings suggest that daily HK L-137 intake can decrease the depth of periodontal pockets in patients undergoing supportive periodontal therapy.
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Randomised clinical trial: the effects of a multispecies probiotic vs. placebo on innate immune function, bacterial translocation and gut permeability in patients with cirrhosis.
Horvath, A, Leber, B, Schmerboeck, B, Tawdrous, M, Zettel, G, Hartl, A, Madl, T, Stryeck, S, Fuchs, D, Lemesch, S, et al
Alimentary pharmacology & therapeutics. 2016;(9):926-935
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Abstract
BACKGROUND Probiotics may correct intestinal dysbiosis and proinflammatory conditions in patients with liver cirrhosis. AIM: To test the effects of a multispecies probiotic on innate immune function, bacterial translocation and gut permeability. METHODS In a randomised, double blind, placebo-controlled study, stable cirrhotic out-patients either received a daily dose of a probiotic powder containing eight different bacterial strains (Ecologic Barrier, Winclove, Amsterdam, The Netherlands) (n = 44) or a placebo (n = 36) for 6 months and were followed up for another 6 months. RESULTS We found a significant but subclinical increase in neutrophil resting burst (2.6-3.2%, P = 0.0134) and neopterin levels (7.7-8.4 nmol/L, P = 0.001) with probiotics but not with placebo. Probiotic supplementation did not have a significant influence on neutrophil phagocytosis, endotoxin load, gut permeability or inflammatory markers. Ten severe infections occurred in total; one during intervention in the placebo group, and five and four after the intervention has ended in the probiotic and placebo group, respectively. Liver function showed some improvement with probiotics but not with placebo. CONCLUSIONS Probiotic supplementation significantly increased serum neopterin levels and the production of reactive oxygen species by neutrophils. These findings might explain the beneficial effects of probiotics on immune function. Furthermore, probiotic supplementation may be a well-tolerated method to maintain or even improve liver function in stable cirrhosis. However, its influence on gut barrier function and bacterial translocation in cirrhotic patients is minimal.
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Oral supplementation with Lactobacillus delbrueckii subsp. bulgaricus 8481 enhances systemic immunity in elderly subjects.
Moro-García, MA, Alonso-Arias, R, Baltadjieva, M, Fernández Benítez, C, Fernández Barrial, MA, Díaz Ruisánchez, E, Alonso Santos, R, Alvarez Sánchez, M, Saavedra Miján, J, López-Larrea, C
Age (Dordrecht, Netherlands). 2013;(4):1311-26
Abstract
Throughout life, there is an aging of the immune system that causes impairment of its defense capability. Prevention or delay of this deterioration is considered crucial to maintain general health and increase longevity. We evaluated whether dietary supplementation with Lactobacillus delbrueckii subsp. bulgaricus 8481 could enhance the immune response in the elderly. This multi-center, double-blind, and placebo controlled study enrolled 61 elderly volunteers who were randomly assigned to receive either placebo or probiotics. Each capsule of probiotics contained at least 3 × 10(7) L. delbrueckii subsp. bulgaricus 8481. Individuals in the study were administered three capsules per day for 6 months. Blood samples were obtained at baseline (time 0), end of month 3, and month 6. We characterized cell subpopulations, measured cytokines by flow cytometry, quantified T cell receptor excision circle (TREC) by real-time PCR (RT-PCR), and determined human β-defensin-2 (hBD-2) concentrations and human cytomegalovirus (CMV) titers by enzyme-linked immunosorbent assay (ELISA). Elderly responded to the intake of probiotic with an increase in the percentage of NK cells, an improvement in the parameters defining the immune risk profile (IRP), and an increase in the T cell subsets that are less differentiated. The probiotic group also showed decreased concentrations of the pro-inflammatory cytokine IL-8 but increased antimicrobial peptide hBD-2. These effects disappeared within 6 months of stopping the probiotic intake. Immunomodulation induced by L. delbrueckii subsp. bulgaricus 8481 could favor the maintenance of an adequate immune response, mainly by slowing the aging of the T cell subpopulations and increasing the number of immature T cells which are potential responders to new antigens.
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Gut microbiota of healthy elderly NSAID users is selectively modified with the administration of Lactobacillus acidophilus NCFM and lactitol.
Björklund, M, Ouwehand, AC, Forssten, SD, Nikkilä, J, Tiihonen, K, Rautonen, N, Lahtinen, SJ
Age (Dordrecht, Netherlands). 2012;(4):987-99
Abstract
Ageing changes gut microbiota composition and alters immune system function. Probiotics, prebiotics and synbiotics may improve the health status of elderly individuals by modifying the intestinal environment and the microbiota composition, and by stimulating the immune system. In this work, we studied the effects of synbiotic supplementation on the gut microbiota of healthy elderly volunteers. Fifty-one elders were randomly assigned to consume either a synbiotic dietary supplement or a placebo in addition to their usual diet for a 2-week period. The synbiotic product consisted of the probiotic Lactobacillus acidophilus NCFM and the prebiotic lactitol and was ingested twice a day, with a total daily dose of 10 g lactitol and 2 × 10(10) cells of probiotic bacteria. Before, during and after the intervention period fecal quantities of six phylogenetic bacterial groups were determined using quantitative PCR, and relative changes in total microbiota composition were assessed by percent guanine-plus-cytosine profiling. The microbiota profiles showed certain relative changes within the microbial community, and indicated an increase of bifidobacteria levels during synbiotic supplementation. Quantification by PCR confirmed the in changes in the microbiota composition; for example increases in total levels of endogenous bifidobacteria and lactobacilli were recorded. Throughout the 6-week study period there was a decrease unrelated to intervention in the Blautia coccoides-Eubacterium rectale bacterial group levels and Clostridium cluster XIVab levels, but this decrease appeared to be halted during the synbiotic intervention. In conclusion, putatively beneficial changes in microbiota were observed in the elderly subjects supplemented with the synbiotic product.
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Probiotic and postbiotic activity in health and disease: comparison on a novel polarised ex-vivo organ culture model.
Tsilingiri, K, Barbosa, T, Penna, G, Caprioli, F, Sonzogni, A, Viale, G, Rescigno, M
Gut. 2012;(7):1007-15
Abstract
BACKGROUND AND AIMS Probiotics and their metabolic products, here called postbiotics, have been proposed as food supplements for a healthier intestinal homeostasis, but also as therapeutic aids in inflammatory bowel disease (IBD) with, however, very little clinical benefit. This may be due to the lack of reliable preclinical models for testing the efficacy of different strains. METHODS The activity of three probiotic strains of Lactobacillus (or a postbiotic) was analysed and compared with a pathogenic strain of Salmonella on a novel organ culture system of human healthy and IBD intestinal mucosa developed in our laboratory. The system maintains an apical to basolateral polarity during stimulation due to the presence of a glued cave cylinder. The cylinder is detached at the end of the experiment and the tissue is processed for histology and immunohistochemistry. Cytokines released from the basolateral side are analysed. RESULTS The model system provides several physiological characteristics typical of a mucosal microenvironment including the presence of an organised mucus layer and an apical to basolateral polarity. Polarised administration of bacteria is critical to control the ensuing immune response as it mimics the physiological entrance of bacteria. The authors show that probiotics are not always beneficial for the healthy host and can also be detrimental in inflamed IBD. This study shows that a potent postbiotic can protect against the inflammatory properties of invasive Salmonella on healthy tissue and also downregulate ongoing inflammatory processes in IBD tissue. CONCLUSIONS Probiotics can have inflammatory activities in both healthy and IBD tissue. Valid preclinical data on proper model systems should therefore be obtained before specific probiotic strains enter the clinics, especially if administered during acute inflammatory responses. Postbiotics may be a safe alternative for the treatment of patients with IBD in the acute inflammatory phase.
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Evidence of immunomodulatory effects of a novel probiotic, Bifidobacterium longum bv. infantis CCUG 52486.
You, J, Yaqoob, P
FEMS immunology and medical microbiology. 2012;(3):353-62
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Abstract
Bifidobacterium longum bv. infantis CCUG 52486 was originally isolated from healthy elderly subjects and demonstrated to have particular ecological fitness and anti-pathogenic effects. Bifidobacteria are commonly associated with immuno-modulatory properties, especially in older people, but this strain has not been investigated for effects on immune function. This study aimed to explore the immunomodulatory effects of this novel probiotic, compared with three commercial strains, B. longum SP 07/3, Lactobacillus rhamnosus GG (L.GG) and Lactobacillus casei Shirota (LcS). Human peripheral blood mononuclear cells (PBMCs) were isolated from fasting blood of young or older volunteers and exposed to probiotic strains or Con A. NK activity and activation, and cytokine release was enhanced by all probiotics with strain specificities. The effect of B. infantis on NK activity was influenced by ageing. Except for L.GG, probiotics increased IFN-γ production to a much greater degree in young subjects and increased IL-6 production to a much greater degree in older subjects. Based on IL-10/IL-12 ratios, B. infantis resulted in the most anti-inflammatory profile of all of the probiotics. These results suggest that B. infantis CCUG 52486 has strong immunomodulatory potential compared with well-known commercial strains and that the immune response to probiotics may be influenced by ageing.
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Effect of probiotic supplementation in the first 6 months of life on specific antibody responses to infant Hepatitis B vaccination.
Soh, SE, Ong, DQ, Gerez, I, Zhang, X, Chollate, P, Shek, LP, Lee, BW, Aw, M
Vaccine. 2010;(14):2577-9
Abstract
Probiotics have been shown to enhance specific immune responses to vaccines. We aim to assess the effect of probiotic supplementation on specific IgG antibody responses to Hepatitis B (HepB) vaccination in infants. Compared to controls, probiotic supplementation improved HepB surface antibody responses in subjects receiving monovalent doses of HepB vaccine at 0, 1 month and a DTPa-HepB combination vaccine at 6 months [placebo (n=28): 187.97 (180.70-195.24), probiotic (n=29): 345.70 (339.41-351.99)mIU/ml] (p=0.069), but not those who received 3 monovalent doses [placebo (n=68): 302.34 (296.31-308.37), probiotic (n=77): 302.06 (296.31-307.81)mIU/ml] (p=0.996). Probiotics may enhance specific antibody responses in infants receiving certain Hepatitis B vaccine schedules.
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Preoperative synbiotic bowel conditioning for elective colorectal surgery.
Horvat, M, Krebs, B, Potrc, S, Ivanecz, A, Kompan, L
Wiener klinische Wochenschrift. 2010;:26-30
Abstract
BACKGROUND Preoperative bowel cleaning for elective colorectal surgery is a routine procedure. Synbiotics (probiotics plus prebiotics) are known for their beneficial effects on gut immune function and maintenance of the gut barrier. The main purpose of this study was to replace preoperative mechanical bowel cleaning with synbiotics and to assess the systemic inflammatory response and clinical outcome in patients undergoing colorectal surgery. PATIENTS AND METHODS A prospective double-blind randomized placebo-controlled trial was conducted in 68 patients. The first group of 20 patients received synbiotics, the second group of 28 patients prebiotics and heat-deactivated probiotics, and the third (control) group of 20 patients mechanical bowel cleaning prior to the operation. RESULTS Significantly higher values of interleukin 6 (IL-6) were detected 72 h after the operation in the synbiotic group (P = 0.025), as well as an increase of fibrinogen at 24 h postoperatively (P = 0.030). No statistical differences were found in leukocytes count, C-reactive protein or the lymphocyte/granulocyte ratio. There were no differences in postoperative complications between the groups. Mean hospital stay was 9.2 days in the prebiotic group, 9.5 days in the control group, and 10.95 days in the synbiotic group. CONCLUSIONS Preoperative administration of prebiotics in elective colorectal surgery appears to have the same protective effect in preventing a postoperative inflammatory response as mechanical bowel cleaning. Further prospective studies are needed to verify the effects of synbiotics.