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1.
Cognitive impairment and CSF proteome modification after oral bacteriotherapy in HIV patients.
Landi, C, Santinelli, L, Bianchi, L, Shaba, E, Ceccarelli, G, Cavallari, EN, Borrazzo, C, Pinacchio, C, Scagnolari, C, Vullo, V, et al
Journal of neurovirology. 2020;(1):95-106
Abstract
OBJECTIVE To investigate whether a probiotic supplementation to cART patients modifies the cerebrospinal fluid (CSF) proteome and improves neurocognitive impairment. METHODS 26 CSF samples from 13 HIV-positive patients [six patients living with HIV (PLHIV) and seven patients with a history of AIDS (PHAIDS)] were analyzed. All patients underwent to neurocognitive evaluation and blood sampling at baseline and after 6 months of oral bacteriotherapy. Immune phenotyping and activation markers (CD38 and HLA-DR) were evaluated on peripheral blood mononuclear cells (PBMC). Plasma levels of IL-6, sCD14, and MIP-1β were detected, by enzyme-linked immunosorbent assay (ELISA). Functional proteomic analysis of CSF sample was conducted by two-dimensional electrophoresis; a multivariate analysis was performed by principal component analysis (PCA) and data were enriched by STRING software. RESULTS Oral bacteriotherapy leads to an improvement on several cognitive test and neurocognitive performance in both groups of HIV-positive subjects. A reduction in the percentage of CD4+CD38+HLA-DR+ T cells was also observed at peripheral level after the probiotic intake (p = 0.008). In addition, the probiotic supplementation to cART significantly modifies protein species composition and abundance at the CSF level, especially those related to inflammation (β2-microglobulin p = 0.03; haptoglobin p = 0.06; albumin p = 0.003; hemoglobin p = 0.003; immunoglobulin heavy chains constant region p = 0.02, transthyretin p = 0.02) in PLHIV and PHAIDS. CONCLUSIONS Our results suggest that oral bacteriotherapy as a supplement to cART could exert a role in the amelioration of inflammation state at peripheral and CNS level.
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2.
Probiotic supplementation promotes a reduction in T-cell activation, an increase in Th17 frequencies, and a recovery of intestinal epithelium integrity and mitochondrial morphology in ART-treated HIV-1-positive patients.
d'Ettorre, G, Rossi, G, Scagnolari, C, Andreotti, M, Giustini, N, Serafino, S, Schietroma, I, Scheri, GC, Fard, SN, Trinchieri, V, et al
Immunity, inflammation and disease. 2017;(3):244-260
Abstract
INTRODUCTION HIV infection is characterized by a persistent immune activation associated to a compromised gut barrier immunity and alterations in the profile of the fecal flora linked with the progression of inflammatory symptoms. The effects of high concentration multistrain probiotic (Vivomixx®, Viale del Policlinico 155, Rome, Italy in EU; Visbiome®, Dupont, Madison, Wisconsin in USA) on several aspects of intestinal immunity in ART-experienced HIV-1 patients was evaluated. METHODS A sub-study of a longitudinal pilot study was performed in HIV-1 patients who received the probiotic supplement twice a day for 6 months (T6). T-cell activation and CD4+ and CD8+ T-cell subsets expressing IFNγ (Th1, Tc1) or IL-17A (Th17, Tc17) were stained by cytoflorimetric analysis. Histological and immunohistochemical analyses were performed on intestinal biopsies while enterocytes apoptosis index was determined by TUNEL assay. RESULTS A reduction in the frequencies of CD4+ and CD8+ T-cell subsets, expressing CD38+ , HLA-DR+ , or both, and an increase in the percentage of Th17 cell subsets, especially those with central or effector memory phenotype, was recorded in the peripheral blood and in gut-associated lymphoid tissue (GALT) after probiotic intervention. Conversely, Tc1 and Tc17 levels remained substantially unchanged at T6, while Th1 cell subsets increase in the GALT. Probiotic supplementation was also associated to a recovery of the integrity of the gut epithelial barrier, a reduction of both intraepithelial lymphocytes density and enterocyte apoptosis and, an improvement of mitochondrial morphology sustained in part by a modulation of heat shock protein 60. CONCLUSIONS These findings highlight the potential beneficial effects of probiotic supplementation for the reconstitution of physical and immunological integrity of the mucosal intestinal barrier in ART-treated HIV-1-positive patients.
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3.
Can Probiotics Reduce Inflammation and Enhance Gut Immune Health in People Living with HIV: Study Designs for the Probiotic Visbiome for Inflammation and Translocation (PROOV IT) Pilot Trials.
Kim, CJ, Walmsley, SL, Raboud, JM, Kovacs, C, Coburn, B, Rousseau, R, Reinhard, R, Rosenes, R, Kaul, R
HIV clinical trials. 2016;(4):147-57
Abstract
OBJECTIVES Despite substantial improvements in HIV outcomes with combination antiretroviral therapy (cART), morbidity and mortality remain above population norms. The gut mucosal immune system is not completely restored by cART, and the resultant microbial translocation may contribute to chronic inflammation, inadequate CD4 T-cell recovery, and increased rates of serious non-AIDS events. Since the microbial environment surrounding a CD4 T cell may influence its development and function, we hypothesize that probiotics provided during cART might reduce inflammation and improve gut immune health in HIV-positive treatment-naïve individuals (PROOV IT I) and individuals with suboptimal CD4 recovery on cART (PROOV IT II). METHODS These prospective, double-blinded, randomized, placebo-controlled, multicenter pilot studies will assess the impact of the probiotic Visbiome at 900 billion bacteria daily. Forty HIV positive cART-naïve men will be randomized in the PROOV IT I study, coincident with antiretroviral initiation, and be followed for 24 weeks. In PROOV IT II, 36 men on cART, but with a CD4 T-cell count below 350 cells/mm(3) will be followed for 48 weeks. The primary outcome for both studies is the comparison of blood CD8 T-cell immune activation. Secondary analyses will include comparison of blood inflammatory biomarkers, microbial translocation, blood and gut immunology and HIV levels, the bacterial community composition, diet, intestinal permeability, and the safety, adherence and tolerability of the study product. DISCUSSION These studies will evaluate the ability of probiotics as a safe and tolerable therapeutic intervention to reduce systemic immune activation and to accelerate gut immune restoration in people living with HIV.
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4.
Immune Response of Healthy Adults to the Ingested Probiotic Lactobacillus casei Shirota.
Harbige, LS, Pinto, E, Allgrove, J, Thomas, LV
Scandinavian journal of immunology. 2016;(6):353-364
Abstract
Daily ingestion of a probiotic drink containing Lactobacillus casei Shirota (LcS; 1.3 × 1010 live cells) by healthy adults for (1) 4-week LcS, (2) 6-week discontinuation of LcS and (3) a final 4 weeks of LcS was investigated. There was a significant increase in expression of the T cell activation marker CD3+ CD69+ in ex vivo unstimulated blood cells at weeks 10 and 14, and there was a significant increase in the NK cell marker CD3+ CD16/56+ in ex vivo unstimulated blood cells at weeks 4, 10 and 14. Expression of the NK cell activation marker CD16/56+ CD69+ in ex vivo unstimulated blood cells was 62% higher at week 10 and 74% higher at week 14. Intracellular staining of IL-4 in ex vivo unstimulated and PMA-/ionomycin-stimulated CD3+ β7+ integrin blood cells was significantly lower at weeks 10 and 14. Intracellular staining of IL-12 in ex vivo unstimulated and LPS-stimulated CD14+ blood cells was significantly lower at weeks 4, 10 and 14. Intracellular staining of TNF-α in LPS-stimulated CD14+ blood cells was significantly lower at weeks 4, 10 and 14. Mucosal salivary IFN-γ, IgA1 and IgA2 concentrations were significantly higher at week 14, but LcS did not affect systemic circulating influenza A-specific IgA or IgG and tetanus-specific IgG antibody levels. In addition to the decrease in CD3+ β7+ integrin cell IL-4 and a reduced CD14+ cell pro-inflammatory cytokine profile, at week 14 increased expression of activation markers on circulating T cells and NK cells and higher mucosal salivary IgA1 and IgA2 concentration indicated a secondary boosting effect of LcS.
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5.
Preliminary results on clinical effects of probiotic Lactobacillus salivarius LS01 in children affected by atopic dermatitis.
Niccoli, AA, Artesi, AL, Candio, F, Ceccarelli, S, Cozzali, R, Ferraro, L, Fiumana, D, Mencacci, M, Morlupo, M, Pazzelli, P, et al
Journal of clinical gastroenterology. 2014;:S34-6
Abstract
GOALS The goal of this study was to evaluate the clinical efficacy of an intake of Lactobacillus salivarius LS01 (DSM 22775) for the treatment of atopic dermatitis (AD) in children. BACKGROUND AD is an inflammatory and pruritic chronic relapsing skin disorder with multifactorial etiopathology. Some evidence suggests that probiotics may improve AD by modulating the immune system and the composition of intestinal microbiota. STUDY A total of 43 patients aged from 0 to 11 years were enrolled in the study (M/F ratio=1:1) and treated with the probiotic strain L. salivarius LS01. Clinical efficacy of probiotic treatment was assessed from baseline by changes in itch index and in the objective SCORAD/SCORAD index. RESULTS Patients being given probiotic treatment showed a significant improvement in clinical parameters (SCORAD and itch values) from baseline. The reduction in SCORAD and itch index observed after 4 weeks of treatment also persisted after the cessation of probiotic supplementation. CONCLUSIONS L. salivarius LS01 seems to be able to improve the quality of life of children affected by AD and, as a consequence, it may have promising clinical and research implications.
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6.
A systems biology approach investigating the effect of probiotics on the vaginal microbiome and host responses in a double blind, placebo-controlled clinical trial of post-menopausal women.
Bisanz, JE, Seney, S, McMillan, A, Vongsa, R, Koenig, D, Wong, L, Dvoracek, B, Gloor, GB, Sumarah, M, Ford, B, et al
PloS one. 2014;(8):e104511
Abstract
UNLABELLED A lactobacilli dominated microbiota in most pre and post-menopausal women is an indicator of vaginal health. The objective of this double blinded, placebo-controlled crossover study was to evaluate in 14 post-menopausal women with an intermediate Nugent score, the effect of 3 days of vaginal administration of probiotic L. rhamnosus GR-1 and L. reuteri RC-14 (2.5×109 CFU each) on the microbiota and host response. The probiotic treatment did not result in an improved Nugent score when compared to when placebo. Analysis using 16S rRNA sequencing and metabolomics profiling revealed that the relative abundance of Lactobacillus was increased following probiotic administration as compared to placebo, which was weakly associated with an increase in lactate levels. A decrease in Atopobium was also observed. Analysis of host responses by microarray showed the probiotics had an immune-modulatory response including effects on pattern recognition receptors such as TLR2 while also affecting epithelial barrier function. This is the first study to use an interactomic approach for the study of vaginal probiotic administration in post-menopausal women. It shows that in some cases multifaceted approaches are required to detect the subtle molecular changes induced by the host to instillation of probiotic strains. TRIAL REGISTRATION ClinicalTrials.gov NCT02139839.
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7.
No evidence of harms of probiotic Lactobacillus rhamnosus GG ATCC 53103 in healthy elderly-a phase I open label study to assess safety, tolerability and cytokine responses.
Hibberd, PL, Kleimola, L, Fiorino, AM, Botelho, C, Haverkamp, M, Andreyeva, I, Poutsiaka, D, Fraser, C, Solano-Aguilar, G, Snydman, DR
PloS one. 2014;(12):e113456
Abstract
BACKGROUND Although Lactobacillus rhamnosus GG ATCC 53103 (LGG) has been consumed by 2 to 5 million people daily since the mid 1990s, there are few clinical trials describing potential harms of LGG, particularly in the elderly. OBJECTIVES The primary objective of this open label clinical trial is to assess the safety and tolerability of 1×1010 colony forming units (CFU) of LGG administered orally twice daily to elderly volunteers for 28 days. The secondary objectives were to evaluate the effects of LGG on the gastrointestinal microbiome, host immune response and plasma cytokines. METHODS Fifteen elderly volunteers, aged 66-80 years received LGG capsules containing 1×1010 CFU, twice daily for 28 days and were followed through day 56. Volunteers completed a daily diary, a telephone call on study days 3, 7 and 14 and study visits in the Clinical Research Center at baseline, day 28 and day 56 to determine whether adverse events had occurred. Assessments included prompted and open-ended questions. RESULTS There were no serious adverse events. The 15 volunteers had a total of 47 events (range 1-7 per volunteer), 39 (83%) of which were rated as mild and 40% of which were considered related to consuming LGG. Thirty-one (70%) of the events were expected, prompted symptoms while 16 were unexpected events. The most common adverse events were gastrointestinal (bloating, gas, and nausea), 27 rated as mild and 3 rated as moderate. In the exploratory analysis, the pro-inflammatory cytokine interleukin 8 decreased during LGG consumption, returning towards baseline one month after discontinuing LGG (p = 0.038) while there was no difference in other pro- or anti-inflammatory plasma cytokines. CONCLUSIONS Lactobacillus rhamnosus GG ATCC 53103 is safe and well tolerated in healthy adults aged 65 years and older. TRIAL REGISTRATION ClinicalTrials.gov NCT 01274598.
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8.
[Probiotics as an items of increasing the effectiveness of treatment of community-acquired pneumonia in adolescents].
Gonchar, NV, Kassner, LN, Korenev, PB, Il'kovich, IuM, Mogilina, SV, Petrov, LN
Eksperimental'naia i klinicheskaia gastroenterologiia = Experimental & clinical gastroenterology. 2011;(1):78-84
Abstract
The aim of the work was to evaluate the efficiency of microbial probiotics Vitaflor and metabolic probiotic Aktoflor-C in complex treatment of community-acquired pneumonia in adolescents in a hospital. The observation involved 38 children aged 11 to 18 years with radiologically verified community-acquired pneumonia, including 23 boys and 15 girls. Patients were divided in 3 groups. Patients in group 1 (n = 13) simultaneously with the antibiotic therapy received per os Vitaflor probiotic containing symbiotic strains of Lactobacillus acidophilus; patients in group 2 (n = 10) along with antibiotic therapy received per os metabolic probiotic Aktoflor-C, containing low molecular weight exometabolites bacteria; patient of the comparison group (n = 15) received antibiotic therapy only. The effectiveness of the used treatment schemes was assessed on the dynamics of the gut state microbiot acoarding to an extended bacteriological examination of faecal flora, level of saliva IgA secretory (before and after treatment), the dynamics of SF-36 quality of life 1 month after discharge from hospital. Was conducted a study of economic efficiency of different modes of therapy. Results showed that adolescents with community-acquired pneumonia during standard antibiotic therapy indicated development of dysbiotic bowel disturbances in the form of reliable oppression of the bifidobacteria and laktoflora. Dysbiosis of the microbial associations are not conducive to proper implementation of immune and nutritional functions of the intestine that shows the imperfection of rehabilitation of patients with pneumonia according to the evaluation of SF-36 quality of life. Pharmacoeconomic analysis revealed the benefits of probiotic metabolic type "Aktoflor" used in addition to standard therapy of community-acquired pneumonia in adolescents.
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9.
Clinical evidence of benefits of a dietary supplement containing probiotic and carotenoids on ultraviolet-induced skin damage.
Bouilly-Gauthier, D, Jeannes, C, Maubert, Y, Duteil, L, Queille-Roussel, C, Piccardi, N, Montastier, C, Manissier, P, Piérard, G, Ortonne, JP
The British journal of dermatology. 2010;(3):536-43
Abstract
BACKGROUND Lactobacillus johnsonii (La1) has been reported to protect skin immune system homeostasis following ultraviolet (UV) exposure. OBJECTIVES To assess the effects of a dietary supplement (DS) combining La1 and nutritional doses of carotenoids on early UV-induced skin damage. METHODS Three clinical trials (CT1, CT2, CT3) were performed using different UV sources: nonextreme UV with a high UVA irradiance (UV-DL, CT1), extreme simulated solar radiation (UV-SSR, CT2) and natural sunlight (CT3). All three clinical trials were carried out in healthy women over 18 years of age with skin type II-IV. In CT1, early markers of UV-induced skin damage were assessed using histology and immunohistochemistry. In CT2, the minimal erythemal dose (MED) was determined by clinical evaluation and by chromametry. Chromametry was also used to evaluate skin colour. Dermatologists' and subjects' assessments were compiled in CT3. RESULTS A 10-week DS intake prevented the UV-DL-induced decrease in Langerhans cell density and the increase in factor XIIIa+ type I dermal dendrocytes while it reduced dermal inflammatory cells. Clinical and instrumental MED rose by 20% and 19%, respectively, and skin colour was intensified, as shown by the increase in the ΔE* parameter. The efficacy of DS was confirmed by dermatologists and subjects under real conditions of use. CONCLUSIONS Nutritional supplementation combining a specific probiotic (La1) and nutritional doses of carotenoids reduced early UV-induced skin damage caused by simulated or natural sun exposure in a large panel of subjects (n=139). This latter result might suggest that DS intake could have a beneficial influence on the long-term effects of UV exposure and more specifically on skin photoageing.
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10.
Intestinal and immunological effects of daily oral administration of Lactobacillus salivarius CECT5713 to healthy adults.
Sierra, S, Lara-Villoslada, F, Sempere, L, Olivares, M, Boza, J, Xaus, J
Anaerobe. 2010;(3):195-200
Abstract
There is an increasing interest in the intestinal and immunological effects of probiotics. The aim of the present study is to evaluate the tolerance and beneficial effects in healthy adults of the strain, Lactobacillus salivarius CECT5713 isolated from breast milk. A phase II, randomized, double-blinded, placebo-controlled human clinical trial was carried out in 40 healthy adults. The Probiotic group received a daily dose of 2 x 10(8) CFU of L. salivarius CECT5713 in capsules during 4 weeks while volunteers of the control received only a placebo. Gastrointestinal and immunological parameters were analyzed. Results showed that L. salivarius CECT5713 was well tolerated and no adverse effects were detected. Consumption of the probiotic strain increased fecal lactobacilli counts (7.9+/-0.1 vs. 7.05+/-0.2 CFU/g feces, P=0.001). Also, an improvement in the frequency of defecation (P=0.04) was observed. Probiotic treatment induced significantly the percentage of NK cells and monocytes, as well as the plasmatic levels of immunoglobulins M, A and G, and the regulatory cytokine IL-10 (72.3+/-11.7 in probiotic group vs. 27.3+/-6.4 pg/mL in control group, P<0.01). Thus, it can be concluded that daily administration of L. salivarius CECT5713 to healthy adults is safe and improve gut microbiota and different parameters related to immune response.