Gut Microbiome Dysbiosis is Associated With Human T‐Lymphotropic Virus Type 1 (HTLV‐1) Infection and Disease Progression to HTLV‐1‐Associated Myelopathy/Tropical Spastic Paraparesis: A Cross‐Sectional Study

Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic neuroinflammatory disease. Given the established role of the gut-brain axis in other neurological diseases such as multiple sclerosis, the role of the gut microbiome in the pathogenesis of HAM/TSP remains a critical unexplored area. The aim of this study was to characterize alterations in the gut microbiome associated with HTLV-1 infection and its clinical stages. We performed a cross-sectional analysis of the gut microbiome from 112 Brazilian individuals, including 24 healthy controls and 88 HTLV-1-infected individuals at different disease stages: 38 HAM patients, 17 patients with intermediate syndromes, and 33 asymptomatic carriers. Fecal samples were collected and analyzed using Illumina MiSeq sequencing to assess bacterial composition and diversity. Functional analysis was performed to identify differentially enriched gene categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) modules. Significant dysbiosis was observed in HTLV-1-infected individuals, characterized by reduced bacterial diversity, an inverted Firmicutes/Bacteroidetes ratio, and specific changes in bacterial genera. Notably, HAM patients exhibited decreased <i>Faecalibacterium</i> and increased <i>Ruminococcus_g2</i> abundance. These associations should be interpreted with caution, as patient cohorts were significantly older and differed in sex distribution from healthy controls. Functional analysis revealed 13 differentially enriched gene categories and five KEGG modules that were more abundant in HAM patients, indicating alterations in metabolic processes. These findings provide the first comprehensive insight into gut microbiome changes associated with HTLV-1 infection and disease progression. This study provides the first comprehensive insight into gut microbiome changes associated with HTLV-1 infection and disease progression. The identified microbial signatures and functional alterations highlight potential diagnostic and therapeutic targets for HTLV-1-associated diseases, particularly HAM. These findings open new avenues for further research and clinical applications.