| Autor: |
Barbero-Herranz R; Microbiology Department, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain., Garriga-García M; Endocrinology and Nutrition Service, Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain., Moreno-Blanco A; Microbiology Department, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain.; CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, 28029 Madrid, Spain., Palacios E; Microbiology Department, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain., Ruiz-Sala P; Centro de Diagnóstico de Enfermedades Moleculares (CEDEM), Autonomous University of Madrid (UAM), IdiPaz, 28049 Madrid, Spain.; CIBER de Enfermedades Raras, Instituto de Salud Carlos III, 28049 Madrid, Spain., Vicente-Santamaría S; Endocrinology and Nutrition Service, Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain., Stanescu S; Unidad de Enfermedades Metabólicas Hospital, CSUR, MetabERN, Pediatric Department, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain., Belanger-Quintana A; Unidad de Enfermedades Metabólicas Hospital, CSUR, MetabERN, Pediatric Department, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain., Pintos-Morell G; Vall d'Hebron Institut de Recerca (VHIR), Unidad de Enfermedades Raras, Hospital Vall d'Hebron Barcelona Hospital Campus, Comité Médico Consultivo MPS-Lisosomales, 08035 Barcelona, Spain., Arconada B; Federación Española de Enfermedades Raras (FEDER), 28009 Madrid, Spain., Del Campo R; Microbiology Department, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain.; CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, 28029 Madrid, Spain.; Faculty of Health Sciences, Alfonso X El Sabio University, Villanueva de la Cañada, 28691 Madrid, Spain., Avendaño-Ortiz J; Microbiology Department, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain.; CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, 28029 Madrid, Spain. |
| Abstrakt: |
Sanfilippo syndrome, or mucopolysaccharidosis type III (MPS III), is a rare lysosomal disease caused by congenital enzymatic deficiencies in heparan sulfate (HS) degradation, leading to organ dysfunction. The most severe hallmark of MPS III comprises neurological alterations, although gastrointestinal symptoms (GISs) have also been shown to be relevant in many patients. Here, we explored the contribution of the gut microbiota to MPS III GISs. We analyzed the composition and functionality of the gut microbiota in two MPS III siblings with the same mutation (c.544C > T, c.1080delC, in the SGSH gene) and the same diet, but with differences in their GISs, including recurrent diarrhea in one of them. Using 16S sequencing, we observed that the MPS III patients exhibited decreased alpha diversity and a lower abundance of Lachnospiraceae and Bifidobacteriaceae accompanied by a higher abundance of the Ruminococcaceae and Rikenellaceae families than the healthy control subjects. Comparing siblings, we found an increased abundance of Bacteroidaceae and a lower abundance of Ruminococcaceae and Akkermansiaceae in the GIS-free patient. This patient also had a higher relative abundance of Sus genes ( SusA , SusB , SusE , and SusG ) involved in glycosaminoglycan metabolism. We found higher HS levels in the stool of the two MPS III patients than in healthy volunteers, particularly in the patient with GISs. Functionally, whole fecal metabolites from the patient with GISs induced oxidative stress in vitro in healthy monocytes. Finally, the Bacteroides thetaiotaomicron strain isolated from MPS III stool samples exhibited HS degradation ability. Overall, our results reveal different microbiota compositions and functionalities in MPS III siblings, who exhibited differential gastrointestinal symptomatology. Our study may serve as a gateway to explore the impact of the gut microbiota and its potential to enhance the quality of life in Sanfilippo syndrome patients. |
