P1 Gut Dysbiosis in Hyperammonemic Mice and Motor Incoordination: A New Discernment of the Gut-Brain Axis in Hepatic Encephalopathy

Abstract

Introduction: Ammonia is the most evolving element during the set of hepatic encephalopathy (HE), a neuropsychiatric disease set off defected liver fictions. The link between the direct effect of hyperammonemia and associated gut dysbiosis in the pathogenesis of HE is not very well established. Thus, this work aimed to assess motor function in the conditions of hyperammonemia and gut dysbiosis in mice. Methods: 28 Swiss mice have been distributed into 3 groups: 2 weeks (2W) and 4 weeks (4W) hyperammonemic groups fed with an ammonia-rich diet (20% w/w), and the control group pair-fed with a standard diet. Motor performance of the 3 groups was measured through a battery of motor tests. Microbial analysis was then assessed from the intestine of the studied mice. Results: The result has shown motor impairment for hyperammonemic groups. Qualitative and quantitative microbiological analysis revealed decreased bacterial load, diversity, and ratios of both aerobic and facultative anaerobic bacteria. Moreover, a time-dependent cutback of gut bacterial diversity in a treatment-time-dependent way. Conclusion: The provided data showed that ammonia-induced motor in-coordination may develop through possible direct and indirect pathways acting on the gut-brain axis (see Figure 1).Figure 1.: A possible mechanism shown revealed in the study by which hyperammonemia and gut dysbiosis may act through a direct or indirect pathway to set off HE. Hyperammonemia may trigger symptoms of HE via 2 pathways. The direct pathway: by which ammonia gets through the defected blood-brain barrier to the nervous system. The indirect pathway: where the resulting dysbiosis is responsible for reducing BBB integrity, thus increasing the flow of ammonia at central level.