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Metabolomic and bacteriome profiling in HAM/TSP patients

Grant number: 22/09354-9
Support Opportunities:Regular Research Grants
Duration: December 01, 2022 - November 30, 2024
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Sabri Saeed Mohammed Ahmed Al-Sanabani
Grantee:Sabri Saeed Mohammed Ahmed Al-Sanabani
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated researchers:Ana Olívia de Souza ; Augusto Cesar Penalva de Oliveira ; Jorge Simão do Rosário Casseb ; Patricia Bianca Clissa ; Silas Granato Villas Boas ; Youko Nukui

Abstract

The Human T-Lymphotropic Virus Type 1 (HTLV-1)-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is clinically characterized by progressive lower extremity weakness, spasticity, and bladder/bowel sphincter dysfunction. The disease affects 0.25-3.8% of HTLV-1 infected adults, with a mean age at onset of 40-50 years, and a higher prevalence in women than men, with a roughly 3:1 ratio. The main pathological feature of HAM/TSP is chronic inflammation with diffuse degeneration throughout the central nervous system. The pathogenesis of HAM/TSP has been shown to involve strong inflammatory responses in the central nervous system (CNS), with perivascular inflammatory infiltrates in the brain and spinal cord. The pathologic mechanism of HAM/TSP development is still greatly unknown. Several studies have explored the involvement of genetics and the immune system in HTLV-1 infected subjects' susceptibility to developing the disease. Some studies suggest a correlation between HAM/TSP and autoimmune diseases, such as uveitis, arthritis, T-lymphocyte alveolitis, polymyositis, and Sjögren syndrome. The human microbiota, especially the intestinal, has shown to be of essential importance in the pathogenesis of autoimmune diseases, such as Type 1 diabetes, inflammatory intestinal diseases, and rheumatoid arthritis. No study in scientific literature has investigated the influence of bacteriome in the HAM/TSP context. The objective of this study is to assess the gut metagenome and and gut and urine metabolome in patients with HAM/TSP and compare them to HTLV-1 asymptomatic carriers, and healthy control. The technique to be used to characterize the gut bacteriome will be based on the analysis of bacterial 16s rRNA partial gene by Illumina MiSeq next-generation sequencing approach. In addition to feces, urine samples will be examined to identify potential metabolic alterations correlated with the bacteriome in HAM/TSP patients and to establish their true metagenomics structure using gas chromatography-mass spectrometry. If we can show in this study that there is a link between the HAM/TSP disorder and gut dysregulation, these results may not only help us find new biomarkers for diagnosing and treating HAM/TSP, but they may also give us a reason to come up with new complementary treatments for the disorder. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
PESSOA, RODRIGO; CLISSA, PATRICIA BIANCA; SANABANI, SABRI SAEED. The Interaction between the Host Genome, Epigenome, and the Gut-Skin Axis Microbiome in Atopic Dermatitis. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 24, n. 18, p. 17-pg., . (22/09354-9)
PESSOA, RODRIGO; DE SOUZA, DANIELA RAGUER VALADAO; NUKUI, YOUKO; PEREIRA, JULIANA; FERNANDES, LORENA ABREU; MARCUSSO, ROSA NASCIMENTO; DE OLIVEIRA, AUGUSTO CESAR PENALVA; CASSEB, JORGE; DUARTE, ALBERTO JOSE DA SILVA; SANABANI, SABRI SAEED. Small RNA Profiling in an HTLV-1-Infected Patient with Acute Adult T-Cell Leukemia-Lymphoma at Diagnosis and after Maintenance Therapy: A Case Study. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 24, n. 13, p. 15-pg., . (22/09354-9)
DE SOUZA, DANIELA RAGUER VALADAO; PESSOA, RODRIGO; NUKUI, YOUKO; PEREIRA, JULIANA; MARCUSSO, ROSA NASCIMENTO; DE OLIVEIRA, AUGUSTO CESAR PENALVA; CASSEB, JORGE; DUARTE, ALBERTO JOSE DA SILVA; CLISSA, PATRICIA BIANCA; SANABANI, SABRI SAEED. Identification of miRnas with possible prognostic roles for HAM/TSP. VIRULENCE, v. 14, n. 1, p. 16-pg., . (22/09354-9, 11/12297-2, 14/24596-2)

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