Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) has traditionally been considered a neuroimmunological disorder, but recent microbiome data suggest that gut dysbiosis may play a key role in its pathogenesis. In this commentary, we contextualize the first cross-sectional characterization of the gut microbiota across the HTLV-1 clinical spectrum, highlighting a consistent inversion of the Firmicutes-to-Bacteroidetes ratio and a marked depletion of the butyrate-producing genus Faecalibacterium, including Faecalibacterium prausnitzii, from asymptomatic carriers to advanced HAM. I propose a gut–brain axis model in which the loss of key butyrate producers, increased intestinal permeability, and enhanced microbial translocation amplify systemic immune activation and neuroinflammation, potentially creating a vicious cycle with HTLV-1-driven neurogenic bowel dysfunction and constipation. The paradoxical enrichment of Ruminococcus, along with functional shifts in microbial pathways such as pyrimidine metabolism, underscores the need for species- and strain-level resolution, integrated metabolomics, and mechanistic in vivo studies to move beyond associative signatures. Finally, we outline research priorities – longitudinal cohorts, multi-omics, and experimental models – to determine whether specific microbiota configurations predict progression to HAM and to inform microbiota-targeted interventions as adjunctive therapeutic strategies.

HTLV-1, HAM/TSP, Gut–brain axis, Microbiome dysbiosis, Neuroinflammation