Group ViljakainenAntimicrobial drug use in the first decade of life influences saliva microbiota diversity and composition
The study found that frequent lifelong use of anti-microbial medicine shifts bacterial profiles years later, which might have unforeseen health impacts in the future.
The human microbiota contributes to health and well-being. Antimicrobials (AM) have an immediate effect on microbial diversity and composition in the gut, but next to nothing is known about their long-term contribution to saliva microbiota. The objectives of the study were to investigate the long-term impact of AM use on saliva microbiota diversity and composition in preadolescents. The lifetime effects by gender and AMs were compared. Data from 808 randomly selected children in the Finnish Health in Teens (Fin-HIT) cohort with register-based data on AM purchases from the Social Insurance Institution of Finland were used. Saliva microbiota was assessed with 16S rRNA (V3-V4) sequencing. The sequences were aligned to the SILVA ribosomal RNA database and classified and counted using the mothur pipeline. Associations between AM use and alpha-diversity (Shannon index) were identified with linear regression, while associations between beta-diversity (Bray-Curtis dissimilarity) and low, medium or high AM use were identified with PERMANOVA.
Of the children, 53.6% were girls and their mean age was 11.7 (0.4) years. On average, the children had 7.4 (ranging from 0 to 41) AM prescriptions during their lifespan. The four most commonly used AMs were amoxicillin (n = 2622, 43.7%), azithromycin (n = 1495, 24.9%), amoxicillin-clavulanate (n = 1123, 18.7%) and phenoxymethylpenicillin (n = 408, 6.8%). A linear inverse association was observed between the use of azithromycin and Shannon index (b − 0.015, p value = 0.002) in all children, the effect was driven by girls (b − 0.032, p value = 0.001), while not present in boys. Dissimilarities were marked between high, medium and low users of all AMs combined, in azithromycin users specifically, and in boys with amoxicillin use. Amoxicillin and amoxicillin-clavulanate use was associated with the largest decrease in abundance of Rikenellaceae bacteria. AM use in general and phenoxymethylpenicillin specifically were associated with a decrease of Paludibacter and pathways related to amino acid degradations differed in proportion between high and low AM users.
In summary, a systematic approach utilizing reliable registry data on lifetime use of AMs demonstrated long-term effects on saliva microbiota diversity and composition. These effects are gender- and AM-dependent. The study found that frequent lifelong use of anti-microbial medicine shifts bacterial profiles years later, which might have unforeseen health impacts in the future. Our findings emphasize a concern for high azithromycin use, which substantially decreases bacterial diversity and affects composition as well. Further studies are needed to determine the clinical implications of the findings.
Raju SC, Viljakainen H, Figueiredo RAO, Neuvonen PJ, Eriksson JG, Weiderpass E, Rounge TB. Antimicrobial drug use in the first decade of life influences saliva microbiota diversity and composition. Microbiome. 2020 Aug 21;8(1):121. doi: 10.1186/s40168-020-00893-y. PMID: 32825849; PMCID: PMC7441731.