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Treatment with Distinct Antibiotic Classes Causes Different Pulmonary Outcomes on Allergic Airway Inflammation
Gregório Grama Cavalcante1, Anna Gabriella Guimarães2, Camila Pereira Queiroz-Glauss1
1Department of Biochemistry and Immunology, Institute of Biological Science, Federal University of Minas Gerais, Belo Horizonte, Brazil.
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.
Insights
Different antibiotics affect allergic airway inflammation differently. Metronidazole may reduce inflammation by altering gut microbiota and increasing beneficial short-chain fatty acids.
Area of Science:
- Immunology
- Microbiology
- Pulmonology
Background:
- Asthma is a chronic respiratory disease affecting 300 million globally.
- The impact of antibiotic use on asthma development and progression remains unclear.
- This study investigates amoxicillin, trimethoprim/sulfamethoxazole, and metronidazole in a mouse model of allergic airway inflammation.
Purpose of the Study:
- To determine the differential effects of specific antibiotics on experimental allergic airway inflammation.
- To explore the mechanisms underlying these effects, including microbiota and metabolite changes.
Main Methods:
- BALB/c mice were treated with amoxicillin, trimethoprim/sulfamethoxazole, or metronidazole.
- Mice underwent sensitization and challenge with ovalbumin (OVA) to induce allergic airway inflammation.
- Pulmonary function, inflammatory markers, serum IgA, and gut/airway microbiota composition were analyzed.
Main Results:
- Amoxicillin and trimethoprim/sulfamethoxazole exacerbated airway inflammation, increasing hyperresponsiveness and IL-4/IL-6 levels.
- Metronidazole treatment preserved lung function, reduced inflammation, and increased fecal butyrate and propionate.
- Metronidazole modulated gut microbiota, enriching for Akkermansia muciniphila and increasing OVA-specific IgA.
Conclusions:
- Antibiotic choice significantly influences experimental allergic airway inflammation.
- Metronidazole demonstrated a protective effect, potentially via gut microbiota modulation and short-chain fatty acid production.
- Findings highlight the complex interplay between antibiotics, microbiota, and respiratory health.
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