Kishanchand Dayamrita Kollaparampil, Venkatachalam Siddarthan, Alikunju Aneesa Painadath, Deepti Ayswaria, Sivan Unnikrishnan, Sasidharan Baby Chakrapani Pulikkaparambil
Department of Biotechnology, Cochin University of Science and Technology, Kochi, Kerala, India; Centre for Neuroscience, Cochin University of Science and Technology, Kochi, Kerala, India.
Arctic Ecology and Biogeochemistry Division, National Centre for Polar and Ocean Research (NCPOR), Ministry of Earth Sciences, Vasco-da-Gama, Goa, India.
Physiol Behav. 2025 Jun 16;299:115000. doi: 10.1016/j.physbeh.2025.115000.
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.
肠道微生物群失调,即肠道微生物群组成的失衡,会影响各种生理和病理过程。我们提出了一种在小鼠中诱导肠道微生物群失调的优化方法,为研究肠道-器官轴提供了一个有价值的工具。我们使用抗生素鸡尾酒诱导微生物群失调,并表征其对宿主生理和肠道微生物群的影响。我们的分析揭示了细菌多样性和组成的显著变化,测试组中潜在致病属如梭菌属vadinBB60_group_ge和埃希氏菌-志贺氏菌属的丰度增加,而有益微生物如普雷沃氏菌科_UCG-001和毛螺菌科_ge的存在减少。这些变化伴随着预测代谢途径的改变,表明肠道生态系统中存在广泛的功能改变。值得注意的是,我们的微生物群失调模型表现出一种“亚临床”状态,这意味着尽管存在显著的微生物变化和生理变化——包括粪便含水量增加、胃肠道转运时间延长、回肠乙酰胆碱酯酶活性升高和盲肠增大——但其特征是没有明显炎症,同时结肠中谷胱甘肽水平升高且肠道屏障完整。这个独特的模型允许探索微生物群破坏对远处器官系统的微妙、长期影响,为研究各种疾病中的肠道-器官轴提供了一个有价值的平台。我们的发现为针对肠道微生物群及其广泛生理影响的治疗干预研究提供了有前景的途径。