Potential prebiotic effects of tamarind seed polysaccharide: comparative evaluation of native versus enzymatic hydrolysates on the restoration of intestinal microbiota in clindamycin‐treated mice

Abstract BACKGROUND Antibiotic‐induced gut dysbiosis poses significant challenges to microbial homeostasis, necessitating effective prebiotic interventions. Given the increasing interest in dietary polysaccharides for modulating microbial imbalance, this study systematically investigates the prebiotic potential of native tamarind seed polysaccharide (NTSP) and its enzymatic hydrolysates (ETSP1, ETSP2) in restoring clindamycin‐disrupted intestinal microbiota in mice, with a focus on the impact of molecular weight on structure–activity relationships. RESULTS Enzymatic depolymerization selectively reduced the molecular weight ( M w from 5.36 × 10 5 to 4.05 × 10 4 g mol −1 ) and enhanced chain rigidity while preserving the galactoxyloglucan backbone, as confirmed by monosaccharide composition, nuclear magnetic resonance, and high‐performance size‐exclusion chromatographic analyses. In vivo , both NTSP and ETSPs ameliorated clindamycin‐induced intestinal dysbiosis via suppression of pathogenic genera (e.g., Escherichia–Shigella , Klebsiella ) and enrichment of beneficial taxa. Notably, the low‐ M w ETSP2 preferentially promoted Lactobacillus and Paludicola , whereas moderate‐ M w ETSP1 enhanced Bacteroides, Flavonifractor , and unclassified_f_Lachnospiraceae , and significantly increased short‐chain fatty acid production, particularly of acetic acid and valeric acid, as quantified by gas chromatography–mass spectrometry. CONCLUSION These findings highlight the critical role of molecular weight in determining prebiotic efficacy, offering insights into the rational design of structure–function optimized polysaccharide‐based therapeutics to combat antibiotic‐associated dysbiosis. © 2026 Society of Chemical Industry.