In conclusion there are only a few

In conclusion, there are only a few experimental reports evaluating the influence of Ramipril on allergy. With the exception of studies using macrolides, most point to their harmful effect on the severity of this disease. Future studies will be crucial to define the impact of antibiotic use on allergy and to understand the molecular cues behind it. In addition, it will be important to define bacterial species positively or negatively correlating with the severity of allergy in patients and test their immunomodulatory properties in vivo using GF animals. Such an approach was recently used by Arietta and colleagues, who identified four bacterial genera (Lachnospira, Rothia, Faecalibacterium, and Veillonella) that were inversely associated with the occurrence of childhood asthma. Using GF mice, the authors also demonstrated a remarkable effect of oral administration of chosen species belonging to these genera on the reduction of allergen-induced neutrophil influx into the BALF [101]. Using a complimentary approach, Fyhrquist et al. identified a positive correlation between the presence of Acinetobacter and anti-inflammatory gene expression in healthy but not atopic individuals. Importantly, administration of Acinetobacter lwoffii into SPF mice conferred protection in an OVA model of asthma [102]. As our knowledge regarding the characteristics of microbial dysbiosis in allergy and asthma expands [103–106], it will be important to combine bioinformatics analyses of samples from patients with in vivo animal models to validate the role of identified candidate species.
Concluding Remarks and Future Perspectives Discovery of antibiotics was one of the breakthroughs in medicine that marked a modern era in public health. Although there is no doubt that antibiotics have saved countless lives to date, the potential negative consequences of their use have only recently started to be unraveled. These include increased susceptibility to certain infections (due to loss of colonization resistance or impaired education of the immune system) and spread of antibiotic resistance. Potentially, widespread use of antibiotics may also be one of the contributing factors in the rapid increase in autoimmunity/allergy occurrence over the past few decades. In the case of allergy and asthma, the epidemiological evidence indeed supports this notion. Unfortunately, experimental studies assessing this issue are scarce. From the handful of reports that exist, most underline a causative relationship between antibiotic use and allergy. However, caution should be taken when interpreting these studies, because they all have certain limitations. First, studies assessing the impact of individual antibiotic classes are scarce, with cephalosporins (based on cefoperazone [85,86]), glycopeptides (based on vancomycin [89,90]), aminoglycosides (based on streptomycin [89,90]), macrolides (based on azithromycin [92], clarithromycin [93], and roxithromycin [94]) and fluoroquinolones (based on enrofloxacin [100]) as the only ones studied. Systematic evaluation of the properties of each antibiotic class on modulation of allergy will be crucial to bring this knowledge into the clinic (see Outstanding Questions). In addition, further research should focus on the development of new generations of antibiotics with a narrowed spectrum of activity. The feasibility of this approach is exemplified by the identification of genus-specific (e.g., Mycobacterium[107] and Staphylococcus[108,109]) or even species-specific compounds (e.g., colicins and pyocins targeting E. coli[110] and P. aeruginosa[111], respectively). Using antibiotics displaying such selectivity would reduce the destruction of the commensal microbiota and could protect against adverse effects of antibiotic treatment. In addition, therapies in place of antibiotics should be further developed. A promising example is phage therapy, which has the potential to allow specific targeting of microbial species within a community [112]. At the same time, there is a strong need for the development of better diagnostic tools for viral infections to prevent the prescription of antibiotics for common viral infections during childhood.