Spatial scaling of metagenomic diversity reveals ecological disruption in the gut microbiome of gout patients

Gout, a painful inflammatory arthritis, is characterized by hyperuricemia and monosodium urate crystal deposition, with growing evidence linking its pathogenesis to gut microbiome dysbiosis. However, traditional diversity metrics fail to capture the complex spatial organization of microbial communities. This study addresses this gap by applying the novel metagenomic Diversity-Area Relationship (m-DAR) model to investigate scaling laws in the gout microbiome—quantifying how metagenomic diversity changes with the number of individuals sampled. Our analysis of gut microbiomes from gout patients and healthy controls revealed fundamental ecological disruptions. We found that gout microbiomes exhibited significantly altered scaling patterns: they showed greater inter-individual dissimilarity (higher z-values) at the level of rare genes (q = 0), but weaker scaling of dominant genes (q = 1–3) compared to healthy controls. Crucially, the maximal accrual diversity (MAD) was substantially lower in gout patients, indicating a severely constrained potential for total microbial gene diversity. Furthermore, profiling of metagenomic functional gene clusters (MFGCs) uncovered widespread functional perturbations, including increased diversity scaling for carbohydrate-active enzymes (CAZy) but decreased scaling in essential metabolic pathways (KEGG, KO). These results demonstrate that the gout gut microbiome is defined by a loss of ecological structure, featuring reduced homogeneity in dominant taxa, expanded rare biosphere variation, and an overall collapsed diversity capacity. This work introduces an ecological framework for characterizing dysbiosis in gout that complements traditional diversity metrics and may inform the development of microbiome-based therapeutic strategies. Further research is needed to translate these ecological patterns into clinical applications.