Intranasal administration of OM-85, a bacterial lysate, alters lung transcriptional profiles and protects against experimental asthma
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ABSTRACT:
PROVIDER: PRJNA705359 | ENA |
REPOSITORIES: ENA
Dataset's files
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| SRR13800700.fastq.gz | Fastqsanger.gz | |||
| SRR13800701.fastq.gz | Fastqsanger.gz | |||
| SRR13800702.fastq.gz | Fastqsanger.gz | |||
| SRR13800703.fastq.gz | Fastqsanger.gz | |||
| SRR13800677.fastq.gz | Fastqsanger.gz |
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Project description:Background: Microbial interventions against allergic asthma have robust epidemiologic underpinnings and the potential to recalibrate disease-inducing immune responses. Oral administration of OM-85, a standardized lysate of human airways bacteria, is widely used empirically to prevent respiratory infections, and a clinical trial is testing its ability to prevent asthma in at-risk children. On the other hand, we previously showed that intra-nasal administration of products from microbe-rich farm environments abrogate experimental allergic asthma. Objectives: To investigate whether direct administration of OM-85 to the airway compartment protects against experimental allergic asthma, and to identify protective cellular and molecular mechanisms activated through this natural route. Methods: BALB/cJ mice (7-8 weeks old) sensitized and challenged with Ovalbumin received OM-85 intra-nasally, and cardinal cellular and molecular asthma phenotypes were measured. Murine lung gene expression was profiled by RNA-sequencing. Results: Airway administration of OM-85 suppressed allergic asthma and altered the transcriptome profile in unfractionated lung tissue. Conclusion We provide the first demonstration that administration of a standardized bacterial lysate to the airway compartment protects from experimental allergic asthma by engaging multiple immune pathways.
2021-10-19 | GSE167867 | GEO
Project description:OM-85 is a bacterial lysate used in clinical practice to reduce duration and frequency of recurrent respiratory tract infections. Whereas knowledge on its regulatory effects in vivo has substantially advanced, the mechanisms of OM-85 sensing remain inadequately addressed.The purpose of this study was to investigate the transptomic profile of human mo-DCs after ex vivo stimulation with OM-85 at determine to what extent OM-85-induced gene signature in different myeloid cell subsets is dependent on TLR2/TLR4 expression. We also aimed to compare the OM-85-triggered gene signature with the signatures induced by specific TLR2 or TLR4 agonists.
2024-03-11 | GSE260787 | GEO
Project description:OM-85 is a bacterial lysate used in clinical practice to reduce duration and frequency of recurrent respiratory tract infections. Whereas knowledge on its regulatory effects in vivo has substantially advanced, the mechanisms of OM-85 sensing remain inadequately addressed.The purpose of this study was to investigate the transptomic profile of human airway immune cells in the BAL after ex vivo stimulation with OM-85 at the single cell level and determine to what extent OM-85-induced gene signature in different myeloid cell subsets is dependent on TLR2/TLR4 expression.
2024-03-16 | GSE261353 | GEO
Project description:Gene expression profile of human mono-derived DCs stimulated with the bacterial lysate OM-85
| PRJNA1083505 | ENA
Project description:BackgroundMicrobial interventions against allergic asthma have robust epidemiologic underpinnings and the potential to recalibrate disease-inducing immune responses. Oral administration of OM-85, a standardized lysate of human airways bacteria, is widely used empirically to prevent respiratory infections and a clinical trial is testing its ability to prevent asthma in high-risk children. We previously showed that intranasal administration of microbial products from farm environments abrogates experimental allergic asthma.ObjectivesWe sought to investigate whether direct administration of OM-85 to the airway compartment protects against experimental allergic asthma; and to identify protective cellular and molecular mechanisms activated through this natural route.MethodsDifferent strains of mice sensitized and challenged with ovalbumin or Alternaria received OM-85 intranasally, and cardinal cellular and molecular asthma phenotypes were measured. Airway transfer experiments assessed whether OM-85-treated dendritic cells protect allergen-sensitized, OM-85-naive mice against asthma.ResultsAirway OM-85 administration suppressed allergic asthma in all models acting on multiple innate and adaptive immune targets: the airway epithelium/IL-33/ILC2 axis, lung allergen-induced type 2 responses, and dendritic cells whose Myd88/Trif-dependent tolerogenic reprogramming was sufficient to transfer OM-85-induced asthma protection.ConclusionsWe provide the first demonstration that administering a standardized bacterial lysate to the airway compartment protects from experimental allergic asthma by engaging multiple immune pathways. Because protection required a cumulative dose 27- to 46-fold lower than the one reportedly active through the oral route, the efficacy of intranasal OM-85 administration may reflect its direct access to the airway mucosal networks controlling the initiation and development of allergic asthma.
| S-EPMC8901455 | biostudies-literature
Project description:Gene exprssion at single cell level in patients broncoalveolar lavage (BAL) cells stimulated ex vivo with bacterial lysate OM-85
| PRJNA1086544 | ENA
Project description:The emergence of SARS-CoV-2, a novel coronavirus, caused the global Coronavirus disease of 2019 (COVID-19) pandemic. Because SARS-CoV-2 mutates rapidly, vaccines that induce immune responses against viral components critical for target cell infection strongly mitigate but do not abrogate viral spread, and disease rates remain high worldwide. Complementary treatments are therefore needed to reduce the frequency and/or severity of SARS-CoV-2 infections. OM-85, a standardized lysate of 21 bacterial strains often found in the human airways, has immuno-modulatory properties and is widely used empirically in Europe, South America and Asia for the prophylaxis of recurrent upper airway infections in adults and children, with excellent safety profiles. In vitro studies from our laboratory recently demonstrated that OM-85 inhibits SARS-CoV-2 epithelial cell infection by downregulating SARS-CoV-2 receptor expression, raising the possibility that this bacterial extract might eventually complement the current COVID-19 therapeutic toolkit. Here we discuss how our results and those from other groups are fostering progress in this emerging field of research.
| S-EPMC9926922 | biostudies-literature
Project description:BackgroundEnvironmental factors play a major role on atopic dermatitis (AD) which shows a constant rise in prevalence in western countries over the last decades. The Hygiene Hypothesis suggesting an inverse relationship between incidence of infections and the increase in atopic diseases in these countries, is one of the working hypothesis proposed to explain this trend.ObjectiveThis study tested the efficacy and safety of oral administration of the bacterial lysate OM-85 (Broncho-Vaxom®, Broncho-Munal®, Ommunal®, Paxoral®, Vaxoral®), in the treatment of established AD in children.MethodsChildren aged 6 months to 7 years, with confirmed AD diagnosis, were randomized in a double-blind, placebo-controlled trial to receive, in addition to conventional treatment with emollients and topical corticosteroids, 3.5mg of the bacterial extract OM-85 or placebo daily for 9 months. The primary end-point was the difference between groups in the occurrence of new flares (NF) during the study period, evaluated by Hazard Ratio (HR) derived from conditional Cox proportional hazard regression models accounting for repeated events.ResultsAmong the 179 randomized children, 170 were analysed, 88 in the OM-85 and 82 in the placebo group. As expected most children in both treatment groups experienced at least 1 NF during the study period (75 (85%) patients in the OM-85 group and 72 (88%) in the placebo group). Patients treated with OM-85 as adjuvant therapy had significantly fewer and delayed NFs (HR of repeated flares = 0.80; 95% confidence interval (CI): 0.67-0.96), also when potential confounding factors, as family history of atopy and corticosteroids use, were taken into account (HR = 0.82; 95% CI: 0.69-0.98). No major side effect was reported, with comparable and good tolerability for OM-85 and placebo.ConclusionsResults show an adjuvant therapeutic effect of a well standardized bacterial lysate OM-85 on established AD.
| S-EPMC5363804 | biostudies-literature
Project description:In Italy, the bacterial lysate OM-85 (Broncho-Vaxom®, Broncho-Munal®, Ommunal®, Paxoral®, Vaxoral®) is registered for the prophylaxis of recurrent respiratory tract infections (RTIs) in adults and children above one year of age, but there are limited data on its use in the paediatric population. We aim to estimate the impact of OM-85 treatment on RTIs and antibiotic prescriptions in children. This study included children aged 1 to 14 years enrolled in Pedianet, a paediatric general practice research database, from January 2007 to June 2017, having at least one prescription of OM-85. Children with less than 12 months of follow-up before (PRE period) and after (POST period) the OM-85 prescription were excluded. The frequency of antibiotic prescriptions and the frequency of RTI episodes in the PRE and POST periods were compared through the post-hoc test. Subgroup analysis was performed in children with recurrent RTIs. 1091 children received 1382 OM-85 prescriptions for a total follow-up of 619,525.5 person-years. Overall, antibiotic prescriptions decreased from a mean of 2.8 (SD (standard deviation) 2.7) prescriptions in the PRE period to a mean of 2.2 (SD 2.6) prescriptions in the POST period (p < 0.0001). RTIs decreased from a mean of 3.4 (SD 2.9) episodes in the PRE period to a mean of 2.5 (SD 2.6) episodes in the POST period (p < 0.0001). No change in antibiotic class was noted, and co-amoxiclav remained the preferred therapy in 28% of cases, followed by amoxicillin. These results were confirmed among children with recurrent RTIs. OM-85 is effective in preventing both antibiotic prescriptions and RTIs in children.
| S-EPMC8297025 | biostudies-literature
Project description:To describe microbiota profiles considering potential influencing factors in pre-school children with recurrent respiratory tract infections (rRTIs) and to evaluate microbiota changes associated with oral bacterial lysate OM-85 treatment, we analyzed gut and nasopharynx (NP) microbiota composition in patients included in the OM-85-pediatric rRTIs (OMPeR) clinical trial (https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-002705-19/IT). Relative percentage abundance was used to describe microbiota profiles in all the available biological specimens, grouped by age, atopy, and rRTIs both at inclusion (T0) and at the end of the study, after treatment with OM-85 or placebo (T1). At T0, Firmicutes and Bacteriodetes were the predominant genera in gut and Proteobacteria, Firmicutes, and Actinobacteria were the predominant genera in NP samples. Gut microbiota relative composition differed with age (<2 vs. ≥2 years) for Firmicutes, Proteobacteria, Actinobacteria (phyla) and Bifidobacterium, Ruminococcus, Lachnospiraceae (genera) (p < 0.05). Moraxella was more enriched in the NP of patients with a history of up to three RTIs. Intra-group changes in relative percentage abundance were described only for patients with gut and NP microbiota analysis available at both T0 and T1 for each study arm. In this preliminary analysis, the gut microbiota seemed more stable over the 6-month study in the OM-85 group, whose mean age was lower, as compared to the placebo group (p = 0.004). In this latter group, the relative abundance of Bacteroides decreased significantly in children ≥2 years. Some longitudinal significant differences in genera relative abundance were also detected in children of ≥2 years for NP Actinobacteria, Haemophilus, and Corynebacterium in the placebo group only. Due to the small number of patients in the different sub-populations, we could not identify significant differences in the clinical outcome and therefore no associations with microbiota changes were searched. The use of bacterial lysates might play a role in microbiota rearrangement, but further data and advanced analysis are needed to prove this in less heterogeneous populations with higher numbers of samples considering the multiple influencing factors such as delivery method, age, environment, diet, antibiotic use, and type of infections to ultimately show any associations with prevention of rRTIs.
| S-EPMC9425436 | biostudies-literature