Drug and probiotics-based intervention strategies for the restoration of gut microbiome dysbiosis

The gut microbiota is a highly complex and intrinsically dynamic ecosystem that undergoes significant changes throughout an individual’s lifetime, influenced by various factors such as diet and lifestyle. Despite its adaptability, the microbiota's balance can be disrupted, leading to a dysbiotic state frequently associated with chronic non-communicable diseases (NCDs) such as obesity, diabetes and cancer. Addressing this imbalance is critical, and interventions such as novel bioactive compounds and next-generation probiotics offer promising avenues for restoring microbial homeostasis. This thesis presents two studies focusing on drug- and probiotics-based strategies aimed at re-establishing eubiosis within the gut microbiota. The first study evaluated the efficacy of four novel compounds in vitro using the Batch Gut Model Cultures assay, specifically targeting antibiotic-resistant Clostridioides difficile. Results demonstrated that certain compounds effectively reduced the target pathogen while enhancing gut microbial diversity. Moreover, the Batch Gut Model Cultures assay proved to be both time- and resource- efficient, retaining robust methodological effectiveness. The second study investigated the impact of an ad hoc microbial consortium as next- generation probiotics on mitigating early weaning effects using an in vivo murine model. Early weaning, increasingly common in Western countries, is recognized as a contributing factor to the onset of numerous NCDs. Findings revealed that this microbial intervention reduced local and systemic inflammation while promoting beneficial bacterial taxa (e.g., Lactobacillus) in the murine gut. Furthermore, the study underscores the utility of this approach as a mouse model for early weaning, addressing the current lack of research linking gut microbiota dynamics to early weaning outcomes. In conclusion, these studies provided foundational insights into the potential of in vitro and in vivo approaches to assess the restoration of gut eubiosis. They could pave the way for future research to further explore innovative strategies to address the dysbiotic layout and its associated health challenges.