Remodelling the gut ecosystem: a dysbiosis model to elucidate gut-organ axis dynamics in mice

Gut dysbiosis, an imbalance in intestinal microbiota composition, influences various physiological and pathological processes. We present a refined method to induce gut dysbiosis in mice, offering a valuable tool for investigating the gut-organ axis. Using an antibiotic cocktail, we induced dysbiosis and characterised its effects on host physiology and gut microbiota. Our analysis revealed significant alterations in bacterial diversity and composition, with the test group showing an increased abundance of potentially pathogenic genera like Clostridia_vadinBB60_group_ge and Escherichia-Shigella and decreased presence of beneficial microbes such as Prevotellaceae_UCG-001 and Muribaculaceae_ge. These changes were accompanied by shifts in predicted metabolic pathways, suggesting widespread functional alterations in the gut ecosystem. Notably, our dysbiosis model exhibited a 'subclinical' state, meaning that despite significant microbial shifts and physiological changes - including increased faecal water content, prolonged gastrointestinal transit time, elevated ileal acetylcholinesterase activity, and enlarged cecum - it was characterized by the absence of overt inflammation, alongside increased glutathione levels in the colon and an intact gut barrier. This unique model allows for exploring subtle, long-term effects of microbiome disruption on distant organ systems, providing a valuable platform for investigating the gut-organ axis in various diseases. Our findings offer promising avenues for research into therapeutic interventions targeting the gut microbiome and its extensive physiological impacts.