Ricerc@Sapienza

Huntington disease (HD) is a neurodegenerative disorder due to a trinucleotide expansion in htt gene encoding huntingtin (htt), a protein widely expressed in human tissues. The accumulation in brain parenchyma leads to molecular dysregulation and cellular dysfunction, which determine movement disorders, cognitive impairment and psychiatric symptoms. Mutant htt accumulates in peripheral tissues too, such as the enteric nervous system, causing intestinal dysfunction. Gastrointestinal tract communicates reciprocally with Central Nervous System (CNS) through non-pathogenic bacteria (microbiota) (microbiota-gut-brain axis). Alterations of gut microbiota (gut dysbiosis) may increase intestinal and BBB permeability. Disruption of gut microbiota was reported in some neurological disorders such as Multiple Sclerosis, Alzheimer and Parkinson diseases. There are no studies on gut dysfunction in HD humans, but evidences of gut dysbiosis in transgenic models of HD, seem to be promising for future studies on humans. Moreover, weight loss, a preponderant symptom in HD, could be influenced by gut dysbiosis. Dysbiosis appear to co-occur with Intestinal permeability changes, leading to pathogenic cascades both in gut and in faraway tissues. However, only few studies explored directly intestinal permeability (IP).
Our aim is to demonstrate gut dysfunction, through the evaluation of IP, in HD patients. We will enrol 10 symptomatic HD patients and 10 pre-symptomatic, compared with 20 healthy controls (HCs). They will collect urines before and after the ingestion of a multi-sugar solution. We will test IP dosing urinary concentration of each sugar and calculating lactulose-mannitol ratio in urine (a general indicator of abnormalities of intestinal mucosa). Therefore, the purpose of the study is to identify different profile of IP in HD patients compared with HCs, which could figure out a correlation between gut dysfunction and disease course.