The baseline microbiota may explain why the response to exogenous interventions that target gut microbes shows high intra- and inter-individual variability. Among the factors that can drive a perturbed gut microbiota composition, the profound effect of antibiotics have been widely studied. However, microbiome responses to antibiotics and their long-lasting effects on the host remain poorly characterized.
A new mice study, led by Dr. Harry Sokol from Sorbonne University and the French National Research Institute for Agriculture, Food and Enviroment (Paris, France), shows that amoxicillin-clavulanate leads to personalized changes in gut microbiota composition and colonic transcriptome in mice.
The researchers sought to explore the differential response of human microbiomes to the commonly prescribed antibiotic amoxicillin-clavulanate. To do this, germ-free mice humanized with the gut microbiota of two unrelated healthy donors were treated with amoxicillin-clavulanate for 7 days.
The gut microbiome and colonic transcriptome analysis before and after antibiotics revealed different responses depending on the donors’ baseline gut microbiota, especially in the recovery period. While recipient mice from the first donor showed a gut microbiota dominated by Prevotella and Faecalibacterium (clustering of samples with the Prevotella enterotype), recipient mice from the second donor showed a gut microbial profile enriched in Bacteroides and Parabacteroides (clustering of samples with the Bacteroides enterotype).
More interestingly, the response to antibiotic treatment in terms of abundant genera was markedly different between the two donor groups. Recipient mice from the first donor showed a destabilized gut microbiota with Clostridium XIVb, Roseburia, Dorea, Blautia and Prevotella being affected, while recipient mice from the second donor showed a more stable gut microbiota profile with only the genus Ruminococcus increasing significantly at 18 days post antibiotics.
Thus, whereas some associations were found between changes in the gut microbiota structure and specific genera in mice from the first donor, overall, the effects of antibiotics in the second group of mice were no different compared with baseline microbiota. Taken together, these findings show less resilience in the first donor’s gut microbiota that impeded returning to baseline after antibiotic treatment, whereas mice receiving gut microbiota from the second donor were much more resilient to antibiotic administration.
At the colonic transcriptome level, antibiotic treatment led to profound alterations in gene expression—especially between the early period after antibiotic administration and recovery—that showed an overlap in both groups regardless of baseline gut microbiota composition. Specifically, an increase in pathways related to biological adhesion and sensing was observed, which the authors suggested could be a rebound response after the perturbation of gut microbiota by antibiotics. It should be acknowledged that although gene expression patterns in response to antibiotics were similar in both groups, the magnitude of gut microbiota perturbation was higher in the first donor group.
It is known that the human gut microbiota structure’s recovery following antibiotic treatment is highly variable between individuals. However, there has been little study regarding the impact on the host of gut microbiota changes resulting from antibiotic perturbation. These new findings in mice reveal how inter-individual variation in the gut microbiota may contribute to personalized responses following gut microbiota disturbance caused by antibiotics. These results add to the growing evidence of the gut microbiome’s involvement in personalized responses to environmental factors.
Reference:
Lavelle A, Hoffmann TW, Pham HP, et al. Baseline microbiota composition modulates antibiotic-mediated effects on the gut microbiota and host. Microbiome. 2019; 7(1):111. doi: 10.1186/s40168-019-0725-3.
