Linking dietary fiber to human malady through cumulative profiling of microbiota disturbance

Abstract Dietary fiber influences the composition and metabolic activity of microbial communities, impacting disease development. Current understanding of the intricate fiber‐microbe‐disease tripartite relationship remains fragmented and elusive, urging a systematic investigation. Here, we focused on microbiota disturbance as a robust index to mitigate various confounding factors and developed the Bio‐taxonomic Hierarchy Weighted Aggregation (BHWA) algorithm to integrate multi‐taxonomy microbiota disturbance data, thereby illuminating the complex relationships among dietary fiber, microbiota, and disease. By leveraging microbiota disturbance similarities, we (1) classified 32 types of dietary fibers into six functional subgroups, revealing correlations with fiber solubility; (2) established associations among 161 diseases, uncovering shared microbiota disturbance patterns that explain disease co‐occurrence (e.g., type II diabetes and kidney diseases) and distinct microbiota patterns that discern symptomatically similar diseases (e.g., inflammatory bowel disease and irritable bowel syndrome); (3) designed a body‐site‐specific microbiota disturbance scoring scheme, computing a disturbance score ( DS ) for each disease and highlighting the pronounced capacity of Crohn's disease to disturb gut microbiota ( DS = 14.01) in contrast with food allergy's minimal capacity ( DS = 0.74); (4) identified 1659 fiber‐disease associations, predicting the potential of dietary fiber to modulate specific microbiota changes associated with diseases of interest; (5) established murine models of inflammatory bowel disease to validate the preventive and therapeutic effects of arabinoxylan that notably perturbed the Bacteroidetes and Firmicutes phyla, as well as the Bacteroidetes and Lactobacillus genera, aligning with our model predictions. To enhance data accessibility and facilitate targeted dietary intervention development, we launched an interactive webtool—mDiFiBank at https://mdifibank.org.cn/ .