Bifidobacterium animalis ssp. Lactis 420 Mitigates Autoimmune Hepatitis Through Regulating Intestinal Barrier and Liver Immune Cells.

Autoimmune hepatitis (AIH) is an immune-mediated inflammatory liver disease of uncertain cause. Accumulating evidence shows that gut microbiota and intestinal barrier play significant roles in AIH thus the gut-liver axis has important clinical significance as a potential therapeutic target. In the present study, we found that Bifidobacterium animalis ssp. lactis 420 (B420) significantly alleviated S100-induced experimental autoimmune hepatitis (EAH) and modulated the gut microbiota composition. While the analysis of clinical specimens revealed that the fecal SCFA quantities were decreased in AIH patients, and B420 increased the cecal SCFA quantities in EAH mice. Remarkably, B420 application improved intestinal barrier function through upregulation of tight junction proteins in both vitro and vivo experiments. Moreover, B420 decreased the serum endotoxin level and suppressed the RIP3 signaling pathway of liver macrophages in EAH mice thus regulated the proliferation of Th17 cells. Nevertheless, the inhibition effect of B420 on RIP3 signaling pathway was blunted in vitro studies. Together, our results showed that early intervention with B420 contributed to improve the liver immune homeostasis and liver injury in EAH mice, which might be partly due to the protection of intestinal barrier. Our study suggested the potential efficacy of probiotics application against AIH and the promising therapeutic strategies targeting gut-liver axis for AIH.

Bifidobacterium animalis subsp lactis HN019 presents antimicrobial potential against periodontopathogens and modulates the immunological response of oral mucosa in periodontitis patients.

OBJECTIVE: To evaluate the effects of Bifidobacterium animalis subsp. lactis HN019 (HN019) on clinical periodontal parameters (plaque accumulation and gingival bleeding), on immunocompetence of gingival tissues [expression of beta-defensin (BD)-3, toll-like receptor 4 (TLR4), cluster of differentiation(CD)-57 and CD-4], and on immunological properties of saliva (IgA levels) in non-surgical periodontal therapy in generalized chronic periodontitis (GCP) patients. Adhesion to buccal epithelial cells (BEC) and the antimicrobial properties of HN019 were also investigated. MATERIALS AND METHODS: Thirty patients were recruited and monitored clinically at baseline (before scaling and root planing-SRP) and after 30 and 90 days. Patients were randomly assigned to Test (SRP+Probiotic, n = 15) or Control (SRP+Placebo, n = 15) group. Probiotic lozenges were used for 30 days. Gingival tissues and saliva were immunologically analyzed. The adhesion of HN019 with or without Porphyromonas gingivalis in BEC and its antimicrobial properties were investigated in in vitro assays. Data were statistically analyzed (p<0.05). RESULTS: Test group presented lower plaque index (30 days) and lower marginal gingival bleeding (90 days) when compared with Control group. Higher BD-3, TLR4 and CD-4 expressions were observed in gingival tissues in Test group than in Control group. HN019 reduced the adhesion of P. gingivalis to BEC and showed antimicrobial potential against periodontopathogens. CONCLUSION: Immunological and antimicrobial properties of B. lactis HN019 make it a potential probiotic to be used in non-surgical periodontal therapy of patients with GCP. CLINICAL RELEVANCE: B. lactis HN019 may be a potential probiotic to improve the effects of non-surgical periodontal therapy. Name of the registry and registration number (ClinicalTrials.gov): "Effects of probiotic therapy in the treatment of periodontitis"-NCT03408548.

Bifidobacterium lactis BB-12 Attenuates Macrophage Aging Induced by D-Galactose and Promotes M2 Macrophage Polarization.

Immunosenescence comprises a set of dynamic changes occurring in innate and adaptive immune systems, and macrophage aging plays an important role in innate and adaptive immunosenescence. However, function and polarization changes in aging macrophages have not been fully evaluated, and no effective method for delaying macrophage senescence is currently available. The results of this study reveal that D-galactose (D-gal) can promote J774A.1 macrophage senescence and induce macrophage M1 polarization differentiation. Bifidobacterium lactis BB-12 can significantly inhibit J774A.1 macrophage senescence induced by D-gal. IL-6 and IL-12 levels in the BB-12 groups remarkably decreased compared with that in the D-gal group, and the M2 marker, IL-10, and Arg-1 mRNA levels increased in the BB-12 group. BB-12 inhibited the expression of p-signal transducer and activator of transcription 1 (STAT1) and promoted p-STAT6 expression. In summary, the present study indicates that BB-12 can attenuate the J774A.1 macrophage senescence and induce M2 macrophage polarization, thereby indicating the potential of BB-12 to slow down immunosenescence and inflamm-aging.

Effects of Lactobacillus rhamnosus HN001 in early life on the cumulative prevalence of allergic disease to 11 years.

BACKGROUND: In a two-centre randomized placebo-controlled trial of Lactobacillus rhamnosus HN001 (HN001) (6 × 109 colony-forming units [cfu]) or Bifidobacterium lactis HN019 (HN019) (9 × 109 cfu) taken daily from 35-week gestation to 6 months' post-partum in mothers while breastfeeding and from birth to age 2 years in infants, we showed that HN001 significantly protected against eczema development at 2, 4 and 6 years and atopic sensitization at 6 years. There was no effect of HN019. We report here the findings for 11 year outcomes. METHODS: At age 11 years, eczema was defined as previously using the UK Working Party's Diagnostic Criteria. Asthma, wheeze, hay fever and rhinitis were defined based on the International Study of Asthma and Allergies in Childhood (ISAAC) questions. Atopic sensitization was defined as one or more positive responses (mean wheal diameter ≥3 mm) to a panel of food and aeroallergens. Analysis was intention-to-treat using hazard ratios to assess probiotic effects on the 11-year lifetime prevalence and relative risks for point or 12-month prevalence at 11 years. RESULTS: Early childhood HN001 supplementation was associated with significant reductions in the 12-month prevalence of eczema at age 11 years (relative risk [RR] = 0.46, 95% CI 0.25-0.86, P = 0.015) and hay fever (RR = 0.73, 95% CI 0.53-1.00, P = 0.047). For the lifetime prevalence, HN001 was associated with a significant reduction in atopic sensitization (hazard ratio [HR] = 0.71, 95% CI 0.51-1.00, P = 0.048), eczema (HR = 0.58, 95% CI 0.41-0.82, P = 0.002) and wheeze (HR = 0.76, 95% CI 0.57-0.99, P = 0.046). HN019 had no significant effect on these outcomes. CONCLUSION: This is the first early probiotic intervention to show positive outcomes for at least the first decade of life across the spectrum of allergic disease.

Adjuvant treatment with a symbiotic in patients with inflammatory non-allergic rhinitis.

Inflammatory non-allergic rhinitis (INAR) is characterized by the presence of an inflammatory infiltrate and a non-IgE-mediated pathogenesis. This retrospective, controlled, multicentre study investigated whether a symbiotic, containing Lactobacillus acidophilus NCFM, Bifidobacterium lactis, and fructo-oligosaccharides (Pollagen®, Allergy Therapeutics, Italy), prescribed as adjunctive therapy to a standard pharmacological treatment, was able to reduce symptom severity, endoscopic features, and nasal cytology in 93 patients (49 males and 44 females, mean age 36.3±7.1 years) with INAR. The patients were treated with nasal corticosteroid, oral antihistamine, and isotonic saline. At randomization, 52 patients were treated also with symbiotic as adjunctive therapy, whereas the remaining 41 patients served as controls. Treatment lasted for 4 weeks. Patients were visited at baseline, after treatment, and after 4-week follow-up. Adjunctive symbiotic treatment significantly reduced the percentages of patients with symptoms and endoscopic signs, and diminished inflammatory cells. In conclusion, the present study demonstrates that a symbiotic was able, as adjuvant treatment, to significantly improve symptoms, endoscopic feature, and cytology in patients with INAR, and its effect may be long lasting.

Long-term safety and efficacy of perinatal probiotic intervention: Evidence from a follow-up study of four randomized, double-blind, placebo-controlled trials.

BACKGROUND: Societies worldwide are faced with a progressive increase in immune-mediated health problems such as allergic, autoimmune, and inflammatory diseases, as well as obesity. Perinatal administration of specific probiotic bacteria is an attractive approach in reducing the risk of these conditions, but long-term efficacy and safety data are lacking. The aim here was to evaluate the clinical benefit and long-term safety of specific probiotics administered during the perinatal period. METHODS: The probiotic strains used were Lactobacillus rhamnosus GG, Bifidobacterium lactis Bb-12, Lactobacillus paracasei ST11, and Bifidobacterium longum BL999. The children involved have subsequently undergone prospective long-term follow-up. In addition to physical examination, data were collected by structured questionnaires on non-communicable diseases and continued probiotic use, and growth data from welfare clinics and school nurses. RESULTS: Altogether 303 mother-infant pairs were included in the analysis. Seventy-six of 163 (47%) children receiving perinatal probiotics had developed allergic disease compared with 79 of 140 (56%) receiving placebo (OR 0.67, 95% confidence intervals [CI] 0.43-1.06, p = 0.09). Fifty-nine of 133 (44%) children receiving L. rhamnosus GG perinatally had developed allergic disease, OR 0.62, 95% CI 0.38-0.99, p = 0.047, as compared to placebo. We found no differences in growth or non-communicable disease prevalence between children receiving perinatally probiotics or placebo. CONCLUSIONS: Perinatal probiotic administration is safe in long-term follow-up. Children receiving L. rhamnosus GG perinatally tended to have decreased allergy prevalence.

Probiotic Yogurt Culture Bifidobacterium Animalis Subsp. Lactis BB-12 and Lactobacillus Acidophilus LA-5 Modulate the Cytokine Secretion by Peripheral Blood Mononuclear Cells from Patients with Ulcerative Colitis.

BACKGROUND: There are some evidences for the immunomodulation disorders in the response to intestinal microbiota in inflammatory bowel disease. Yogurt is a fermented milk product made with a starter culture consisting of different probiotics which could be colonized in intestine. However, the role of probiotics in the aetiopathogenesis of ulcerative colitis (UC) has not been clarified. To determine how the immune system responds to these bacteria this study was planned. METHODS: Bifidobacterium lactis BB-12 (B. lactis) and Lactobacillus acidophilus LA-5 (L. acidophilus) were cultivated on MRS broth. PBMCs of 36 UC patients were separated by Ficoll-Hypaque centrifugation and co-cultured with different concentrations of UV killed bacteria in RPMI-1 640 plus 10% FCS for 48/72 h. IL-10, TGF-ß, IFN-γ and TNF-α were measured in supernatant of PBMCs by ELISA. RESULTS: Both bacteria significantly augmented IL-10, TGF-ß, IFN-γ and TNF-α compared to control (p<0.001). The secretion levels of IL-10 and TGF-ß by B. lactis- compared to L. acidophilus-stimulated PBMCs were significantly higher (p<0.05, p<0.01 respectively). The secretion levels of TNF-α and IFN-γ by PBMCs after 72 h were significantly lower compared to 48 h stimulation by B. lactis (p<0.001, p<0.035 respectively). CONCLUSION: These data show that both probiotics may trigger the pro- and anti-inflammatory immune response of UC patients. It seems that IL-10/TGF-ß uprising by B. lactis could be the reason of TNF-α/IFN-γ reduction. Therefore albeit B. lactis still stimulates the effector Th cells but because of more stimulatory effect on Tregs, it could be a good potential therapeutic candidate for further investigation.

Bifidobacterium animalis subsp. lactis in prevention of common infections in healthy children attending day care centers - Randomized, double blind, placebo-controlled study.

BACKGROUND & AIMS: The aim of our study was to investigate the role of Bifidobacterium animalis subsp. lactis (BB-12(®)) in the prevention of common (gastrointestinal and respiratory) infections in healthy children who attend day care centers. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in 210 children who attend day care centers. They were randomly allocated to receive placebo (Placebo group, n = 106) or BB-12(®) at a dose of 10(9) colony-forming units (CFU) (Intervention group, n = 104) during the 3-month intervention period. RESULTS: Intention to treat analysis was used. There were overall 99 infections in Placebo group and 97 in Intervention group (incidence rate ratio = 1.0014, p = 0.992, Poisson regression model). Overall 65 children (61.3%) in Placebo group and 67 (64.4%) in Intervention group had common infections (p = 0.642). Mean number of infections per child was 0.93 (range 0-3) in Placebo group and 0.93 (range 0-3) in Intervention group (p = 0.898). There was no difference in secondary (duration of symptoms, number of children with gastrointestinal and respiratory tract infections, absence from day care center due to infections, use of antibiotics) and exploratory (type of gastrointestinal and respiratory tract infection) endpoints between groups. CONCLUSION: Results of performed study show that BB-12(®) has no effect on the prevention of gastrointestinal and respiratory tract infections in healthy children who attend day care centers.