Disturbance of the gut microbiota during antibiotic stress (therapy): a multi-omic approach

Recent research has disclosed a tight connection between beta-lactam antibiotics, microbial gut metabolism and health but obtaining a complete understanding of this process remains a major goal. Here, we conducted, to the best of our knowledge, the first global comparative OMIC investigation of gut microbial communities in samples of an individual subjected to ß-lactam antibiotic therapy at different time frames. Results indicated a drastic change of the total community at response to AB at the day 11thwhich correlated with changes at the level of metabolites, mRNA transcripts and production of proteins. By contrast, AB-resistant active microbiota remains constant, showing a relevant decrease three days later, which indicate an AB time-delay between total and active bacteria. Forty days after AB therapy, the total community is restored but, surprisingly, the low abundant bacteria (Proteobacteria) become the most active members. This is in agreement with unique metabolomic signatures which indicate that human-gut microbe interactions seem to be restored (or improved) as a consequence of AB therapy. It is worth to mention that as a consequence of AB a drastic under-expression of protein production and an attenuation of the metabolic status occurred irreversibly, in agreement with the biodiversity and richness decreased of the total microbiota. Most likely, at the initial stages, AB-resistant bacteria may become, albeit at lower numbers, the most active bacterial members, but their consequent instability as response to AB therapy produced a re-establishment of the overall community containing new active members that has a connection with the host. A complete reprogramming of the bacterial structure and metabolic status seems to occur most likely at day 11th. Taken together, this study suggests a tighter, more coordinated and complex evolutionary and AB ecology scenario of human gut microbial communities than has been previously assumed.