Elegant approach to intervention of homogalacturonan from the fruits of Ficus pumila L. in colitis: Unraveling the role of methyl esters and acetyl groups.

Oral administration of homogalacturonan (HG) has shown significant potential in anti-colitis activity, yet the therapeutic efficacy of naturally sourced HG still requires enhancement. Herein, HG from the fruits of Ficus pumila L. was modified by chemical methods and the intervention effect of modified HG with different degrees of methyl-esterification (DM) and acetylation (DA) on dextran sulfate sodium-induced colitis in mice was explored. Our results indicated that low-DM HG (DM3 and DM25) primarily mitigated colitis by reducing inflammation (TNF-α, IL-1β, IL-17, and IL-6), while high-DM HG (DM54 and DM94) primarily repaired the intestinal barrier. These effects may be attributed to the differential regulation of gut microbiota by HG with varying DM, such as Lachnospiraceae_NK4A136_group, Lactobacillus, Mucispirillum, Escherichia-Shigella, Bifidobacterium, and Bacteroides. Increased DA reduced the solubility of HG, showing limited anti-inflammatory response but unique advantages in intestinal barrier repair and microbiome regulation (Bifidobacterium, Candidatus_Saccharimonas, Lachnospiraceae_NK4A136_group, Mucispirillum, and Escherichia-Shigella). Furthermore, various structural parameters and substitution degrees showed no significant impact on HG's regulation of oxidative stress reactions. This study emphasized the importance of substituent effect in determining HG's functional role, providing a robust foundation for the design and development of functional polysaccharides for the prevention of intestinal inflammation and other related conditions.