Temporal Multi-Omics Reveals Microbial and Metabolic Succession Following Astilbin Treatment in a Human Colonic Model.

Abstract

Background: Astilbin is a bioactive flavonoid with documented anti-inflammatory properties; however, its sustained interactions with the gut microbiota remain poorly understood. Fecal samples from three healthy donors were pooled and fermented with astilbin in an in vitro human colonic model over 7 days. This exploratory study aimed to characterize the temporal ecological shifts associated with prolonged astilbin exposure. Methods: Time-resolved 16S rRNA gene sequencing, PICRUSt2 functional prediction, BugBase phenotypic inference, and pseudo-targeted metabolomics were integrated to track microbial-metabolic dynamics. Results: Astilbin exposure was associated with a highly coordinated, three-stage microbial succession. Day 3 (D3) emerged as a putative inflection point, where the enrichment of pioneer degraders (Flavonifractor, Bacteroides) was temporally correlated with the appearance of polyphenol cleavage intermediates. This transition featured an early decrease in markers of proteolytic fermentation alongside a transient in vitro lipid-stress response. By D7, the community shifted toward a stable configuration enriched in butyrogenic taxa (Roseburia, Subdoligranulum, Megamonas), with progressive depletion of potentially opportunistic pathogens (Escherichia-Shigella). Multi-omics integration suggested that these structural successions were strongly associated with marked metabolic shifts. Inflammatory lipid markers (e.g., leukotriene B4) showed a characteristic "D3-burst/D7-clearance" pattern, whereas potentially barrier-protective metabolites, particularly 3-indolepropionic acid (3-IPA, log₂FC = 2.00) and urolithin B (log₂FC = 1.18), accumulated substantially. Conclusions: This exploratory study provides valuable high-resolution insights into astilbin's potential as a dynamic ecological modulator. It outlines a temporal framework illustrating how the gut microbiota may shift from proteolytic fermentation toward 3-IPA-associated homeostasis. Although limited by a pooled fecal model and the absence of a vehicle control, these hypothesis-generating findings offer a solid foundation for future in vivo studies and mechanistic validations across diverse human cohorts.