Newswise — Every individual's gut microbiome possesses a distinct assembly of microorganisms, typically enduring stability over extended periods. Nevertheless, it can become disrupted due to elements like alterations in diet, infections, or medications. Notably, antibiotics wield significant sway over the microbiome. Consequently, microorganisms employ diverse resistance mechanisms, prompting the evolution of antibiotic-resistant variations within bacterial populations. Nonetheless, the precise extent, mechanisms, and ecological ramifications of these processes remain inadequately comprehended.
In an extensive metagenomic investigation, Prof. Bärbel Stecher and Prof. Alice McHardy, along with an international team of researchers from DZIF, undertook a study on the evolutionary changes occurring in intestinal bacteria due to repeated antibiotic disruptions. To accomplish this, they employed a gnotobiotic mouse model, where mice were maintained germ-free and consistently colonized with a known consortium of bacteria. This model enabled the researchers to conduct evolutionary studies on individual community members within their natural host under precisely defined and controlled conditions. Over a span of 80 days, the scientists examined the impact of various classes of antibiotics on the microbiome. Utilizing metagenomic analyses, they monitored the selection of potential mutations that could promote antibiotic resistance in the bacterial populations. Subsequently, they scrutinized the characteristics of evolved bacterial clones that were isolated from the communities.
"Through our research, we observed the progression of antibiotic-resistant commensal bacteria in response to repeated antibiotic therapy, resulting in enhanced resilience of the microbial community against specific antibiotics like tetracyclines. Not only did we witness the adaptation of individual microorganisms within the microbiome through evolutionary changes, but we also identified instances of resistance development in individual bacteria, characterized by a deceleration in cell growth. The microbiome, so to speak, adjusts to the treatment and becomes better equipped to withstand its effects," explains Bärbel Stecher, who serves as the coordinator of the Gastrointestinal Infections research area at the German Center for Infection Research (DZIF) and holds the position of professor of Medical Microbiology and Hygiene at the Max von Pettenkofer Institute at Ludwig-Maximilians-Universität München (LMU).
Furthermore, the research team also noticed the stimulation of prophages, which was induced by the administration of specific antibiotics. During this process, lysogenic bacteriophages, whose genetic material is integrated into bacterial genomes, were activated. As a result, these bacteriophages multiplied and caused the lysis of host cells upon the release of new viral particles. "This serves as an illustration of how antibiotics can indirectly impact bacterial survival," explains Dr. Philipp Münch, the primary author of the study.
The study provides compelling evidence of the extensive variability in the microbiome's response to antibiotic treatments. One notable finding is the ecological impact observed, whereby the elimination of a crucial "partner" bacterium within the metabolic network of the gut ecosystem leads to the inhibition of specific microorganisms. This highlights the intricate relationships and interdependencies within the microbiome.
"Given the intricate nature of both direct and indirect responses, it becomes challenging to anticipate which species will be impacted by antibiotic treatment, even in gnotobiotic animal models featuring a well-defined microbial community," summarizes Prof. Alice McHardy, Deputy Coordinator of Bioinformatics and Machine Learning at DZIF and the leader of the Department of Computational Biology for Infection Research at the Helmholtz Centre for Infection Research, which is a DZIF member institution. This emphasizes the complex and unpredictable dynamics within the microbiome in the context of antibiotic interventions.
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