Treatment with Distinct Antibiotic Classes Causes Different Pulmonary Outcomes on Allergic Airway Inflammation Associated with Modulation of Symbiotic Microbiota

Abstract

Background. Asthma is a chronic pulmonary disease that affects about 300 million people worldwide. Previous studies have associated antimicrobial use with allergies, but the real impact of antibiotics on asthma is still elusive. We investigated the potential impact of amoxicillin (Amox), trimethoprim/sulfamethoxazole (TMP/SMX), and metronidazole (Metro) in a murine model of OVA-induced allergic airway inflammation. Methods. BALB/c mice received three cycles of 7 days of antibiotics in drinking water followed by 7 days washout and were sensitized i.p. with OVA/Alum at days 0 and 14. After the end of the last antibiotic washout, the mice were challenged with aerosolized OVA. Pulmonary parameters were evaluated, and serum, BAL, and feces were collected for analysis. Results. Amox- and TMP/SMX-treated animals displayed more severe allergic airway inflammation parameters with increased airway hyperresponsiveness, reduced lung alveolar volume, and increased levels in BAL of IL-4 and IL-6. In contrast, Metro-treated mice showed preserved FEV-50, decreased lung inflammation, and higher levels of butyrate and propionate in their feces. Metro treatment was associated with increased OVA-specific IgA in serum. BAL microbiota was abundant in allergic groups but not in nonallergic controls with the Amox-treated group displaying the increased frequency of Proteobacteria, while Metro and TMP/SMX showed increased levels of Firmicutes. In the gut, we observed the enrichment of Akkermansia muciniphila associated with reduced airway inflammation phenotype in the Metro group, even after the recovery period. Conclusion. Our data suggest that different antibiotic treatments may impact the course of experimental allergic airway inflammation in diverse ways by several mechanisms, including modulation of short-chain fat acids production by intestinal microbiota.

Coccidioidomycosis and Host Microbiome Interactions: What We Know and What We Can Infer from Other Respiratory Infections

“…Absorbable antibiotics can cause direct distal changes to the lung microbiota. Additionally, treatment with different antibiotics results in distinct pulmonary outcomes in allergic airway inflammation [64]. Amoxicillinand trimethoprim/sulfamethoxazole-treated mice display increased airway hyperresponsiveness, reduced lung alveolar volume, and increased levels of proinflammatory cytokines in the bronchioalveolar lavage fluid, indicative of increased inflammation [64].…”

“…Additionally, treatment with different antibiotics results in distinct pulmonary outcomes in allergic airway inflammation [64]. Amoxicillinand trimethoprim/sulfamethoxazole-treated mice display increased airway hyperresponsiveness, reduced lung alveolar volume, and increased levels of proinflammatory cytokines in the bronchioalveolar lavage fluid, indicative of increased inflammation [64]. Metronidazole treatment, on the other hand, is associated with increased antigen-specific IgA in mouse serum associated with decreased asthma prevalence [64].…”

“…Amoxicillinand trimethoprim/sulfamethoxazole-treated mice display increased airway hyperresponsiveness, reduced lung alveolar volume, and increased levels of proinflammatory cytokines in the bronchioalveolar lavage fluid, indicative of increased inflammation [64]. Metronidazole treatment, on the other hand, is associated with increased antigen-specific IgA in mouse serum associated with decreased asthma prevalence [64]. Although pathogen mediated responses may differ from allergic inflammation, these findings highlight that antibacterial agent choice may have different impacts and potential disease outcomes in coccidioidomycosis [64].…”

“…Metronidazole treatment, on the other hand, is associated with increased antigen-specific IgA in mouse serum associated with decreased asthma prevalence [64]. Although pathogen mediated responses may differ from allergic inflammation, these findings highlight that antibacterial agent choice may have different impacts and potential disease outcomes in coccidioidomycosis [64]. Nonetheless, since Valley fever patients are often treated with antibiotics pre-and post-coccidioidomycosis diagnosis, these antibiotics likely cause perturbations on the host microbiota and immune response, making it worthwhile to explore these effects during coccidioidomycosis (Figure 1).…”