Document resource
Background This study aims to elucidate the pathological mechanisms underlying the high incidence of arthritis following infection with chikungunya fever. While the gut-joint axis hypothesis has recently provided a novel perspective for understanding inflammatory arthropathies, its role in acute viral arthritis, such as chikungunya, remains unclear.Methods To address this, we prospectively enrolled 56 patients with acute-phase chikungunya virus infection and 51 healthy controls, integrating metagenomics and metabolomics to systematically characterize the structural, keystone species and metabolic network remodeling of the gut microbiome induced by virus infection. Furthermore, we validated the pathogenic role of the gut microbiota in vivo through fecal microbiota transplantation and viral challenge experiments using a pseudo-germ-free (antibiotic-treated) mouse model (IDDF2026-ABS-0323 Figure 1. Graphical abstract).Results This study identifies chikungunya virus infection as a potent intervenor of the human gut microbiota, causing an ecological imbalance. The analysis of key intestinal species indicates that Christensenella minuta and Phocaeicola vulgatus exhibit high specificity and prevalence, and play a role as keystone symbiotic hubs in the intestinal interaction networks of both healthy (Ctrl) and diseased (ChiF) individuals. Meanwhile, they have been identified as important selected variables between the two groups from the random forest model. Notably, the central role of Christensenella minuta in the microbial network of patients with joint pain presents significant changes compared to that in healthy individuals, indicating that the absence of Christensenella minuta in the intestinal tract of the ChiF population has induced stronger correlations with other microorganisms (IDDF2026-ABS-0323 Figure 2). As the mediation model further establishes a potential causal link between gut microbiome and metabolite, we found the reduction of Christensenella minuta altered steroid hormone metabolism (e.g., androstenedione, IDDF2026-ABS-0323 Figure 3). Subsequently, animal experiments using fecal microbiota transplantation confirm that transplanting the gut microbiota from chikungunya virus patients could independently induce joint-localized inflammation in recipient mice without viral challenge, leading to synovial hyperplasia and early fibrosis (IDDF2026-ABS-0323 Figure 4, IDDF2026-ABS-0323 Figure 5).Conclusions The conclusions indicate that chikungunya virus infection significantly disrupts the intestinal microbial ecology, driving the alteration of specific key bacteria and metabolic dysfunction, which subsequently activates pro-inflammatory pathways via the gut-joint axis and ultimately exacerbates joint pathological damage.Abstract IDDF2026-ABS-0323 Figure 1Abstract IDDF2026-ABS-0323 Figure 2Abstract IDDF2026-ABS-0323 Figure 3Abstract IDDF2026-ABS-0323 Figure 4Abstract IDDF2026-ABS-0323 Figure 5