Probiotics for the airways: Potential to improve epithelial and immune homeostasis.

Probiotics are live microorganisms that, when administered in adequate amounts, confer health benefit on the host. The therapeutic effects of probiotics have been mostly studied in the gastrointestinal tract, but recent evidence points toward the potential of these bacteria to prevent and/or treat chronic airway diseases. In this review, possible mechanisms of action of probiotics in the airways are described, with a particular focus on their capacity to modulate the epithelial barrier function and their mode of interaction with the immune system. Indeed, probiotic bacteria, mostly lactobacilli, can promote the expression and regulation of tight junctions and adherence junctions, resulting in the restoration of a defective epithelial barrier. These bacteria interact with the epithelial barrier and immune cells through pattern recognition receptors, such as Toll-like receptors, which upon activation can stimulate or suppress various immune responses. Finally, the clinical potential of probiotics to treat inflammatory diseases of the upper and lower respiratory tract, and the difference between their mode of application (eg, oral or nasal) are discussed here.

EUFOREA Rhinology Research Forum 2016: report of the brainstorming sessions on needs and priorities in rhinitis and rhinosinusitis.

The first European Rhinology Research Forum organized by the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) was held in the Royal Academy of Medicine in Brussels on 17th and 18th November 2016, in collaboration with the European Rhinologic Society (ERS) and the Global Allergy and Asthma European Network (GA2LEN). One hundred and thirty participants (medical doctors from different specialties, researchers, as well as patients and industry representatives) from 27 countries took part in the multiple perspective discussions including brainstorming sessions on care pathways and research needs in rhinitis and rhinosinusitis. The debates started with an overview of the current state of the art, including weaknesses and strengths of the current practices, followed by the identification of essential research needs, thoroughly integrated in the context of Precision Medicine (PM), with personalized care, prediction of success of treatment, participation of the patient and prevention of disease as key principles for improving current clinical practices. This report provides a concise summary of the outcomes of the brainstorming sessions of the European Rhinology Research Forum 2016.

Impacts of Menstruation, Community Type, and an Oral Yeast Probiotic on the Vaginal Microbiome.

A healthy state of the vaginal microbiome can prevent vaginal disease and promote successful fertilization and healthy pregnancies. Little is known about the stability of the vaginal microbiome and the influence of factors such as diet and probiotics. While less explored, yeast probiotics have an interesting potential because of their immunomodulatory and pathogen inhibition capacities. In this study, we investigated the impact of the oral yeast probiotic Saccharomyces cerevisiae CNCM I-3856 on the vaginal microbiomes of 52 healthy women using 16S and internal transcribed spacer (ITS) amplicon sequencing and quantitative PCR (qPCR). The vaginal fungal loads remained low, even after oral yeast supplementation, complicating the analysis of the vaginal mycobiome. Lactobacillus crispatus and Lactobacillus iners were the most dominant species in our study population and were found to codominate in 23% of the baseline samples. Bifidobacterium, Streptococcus, and Prevotella were also frequently found. The microbiome profiles were dynamic: 69% of women showed a shift in the dominant community members at least once during the 42-day sampling period. In addition, lower Lactobacillus abundances were observed at the time points after menstruation. Higher relative abundances of Lactobacillus with more L. iners-dominated samples and a trend toward lower relative abundances of Prevotella were observed in the probiotic group, but analyses of the effects of the yeast probiotic were complicated by differences already present at the onset of the study. Thus, our findings especially highlighted that the impact of menstruation and the stratification of women based on the dominant vaginal taxa before randomization and inclusion is important for future research: while the impact of the yeast probiotic on vaginal microbiome in healthy women was limited. IMPORTANCE How to define and promote a healthy state of the vaginal microbiome is not well understood. Knowledge of which underlying factors shape the microbial community composition of the vagina and how to modulate them will contribute to vaginal disease prevention and improve fertility. Here, we found that taking the menstrual cycle into account when designing a microbiome study is highly recommended: menstruation also showed to be poses an interesting time point for intervention because of the drop in the abundance of L. crispatus. Furthermore, the early stratification of groups (e.g., placebo versus treatment) according to the dominant taxa can be of high added value since menstruation impacts vaginal taxa differently, i.e., L. iners remains stable, in contrast to L. crispatus.

Multifactorial inhibition of lactobacilli against the respiratory tract pathogen Moraxella catarrhalis.

Probiotics, mainly lactic acid bacteria (LAB), are widely focused on gastrointestinal applications. However, recent microbiome studies indicate that LAB can be endogenous members of other human body sites such as the upper respiratory tract (URT). Interestingly, DNA-based microbiome research suggests an inverse correlation between the presence of LAB and the occurrence of potential pathogens, such as Moraxella catarrhalis, an important URT pathogen linked to otitis media, sinusitis and chronic obstructive pulmonary disease. However, a direct interaction between these microbes has not been explored in detail. This study investigated the direct antipathogenic effects of Lactobacillus species, including several well-documented probiotic strains, on M. catarrhalis using agar-based assays, time course analysis, biofilm assays and minimal inhibitory concentration (MIC) testing. These assays were performed using spent culture supernatans (SCS) at two pHs (4.3 and 7) and D- and/or L-lactic acid at three pHs (2, 4 and 7). In addition, cell line assays for adhesion competition and immunomodulation were used to substantiate the inhibitory effect of lactobacilli against M. catarrhalis. A proportion of Lactobacillus strains, including the model probiotic Lactobacillus rhamnosus GG, showed a strong and direct activity against M. catarrhalis. Screening of the activity of the SCS after different treatments demonstrated that lactic acid has an important antimicrobial activity against this pathogen - at least in vitro - with mean MIC values for D- and L-lactic acid varying between 0.5 and 27 g/l depending on the pH. Furthermore, L. rhamnosus GG also decreased the adhesion of M. catarrhalis to human airway epithelial Calu-3 cells with more than 50%, and the expression of mucin MUC5AC, pro-inflammatory cytokines interleukin (IL)-8, IL-1ß, and tumor necrosis factor-α at least 1.2 fold. This study suggests that several lactobacilli and their key metabolite lactic acid are possible candidates for probiotic therapeutic interventions against URT infections.