Poricoic acid A administered during DSS exposure attenuates acute colitis in mice and is accompanied by barrier-associated changes and endpoint fecal microbiota shifts.

Poricoic acid A (PAA), a lanostane-type triterpenoid associated with Poria-derived medicines, has shown tissue-protective activity, but its effects on epithelial-barrier phenotypes and endpoint fecal microbiota in experimental colitis remain incompletely characterized. Male C57BL/6 mice were exposed to 3% dextran sulfate sodium (DSS) for 7 days and received oral PAA (2.5, 5, or 10 mg/kg/day), sulfasalazine (200 mg/kg/day), or vehicle concomitantly with DSS. Clinical disease indices and colon length were assessed; colonic histology, mucus-positive staining, epithelial ultrastructure, serum lipopolysaccharide (LPS), E-cadherin, and claudin-3 were evaluated; and endpoint fecal microbial communities were profiled by 16S rRNA gene sequencing. DSS caused body-weight loss, increased disease activity, colon shortening, histological injury, mucus depletion, epithelial ultrastructural disruption, increased serum LPS, and reduced colonic E-cadherin and claudin-3. PAA attenuated the clinical and histological changes, with the most consistent effects at 10 mg/kg/day, the highest dose tested. This group also showed better-preserved epithelial ultrastructure, lower serum LPS, and higher E-cadherin and claudin-3 signals than the DSS group. Endpoint sequencing showed higher richness-related indices in the PAA-H group than in the DSS group, including Chao1, ACE, observed species, and Faith's phylogenetic diversity, whereas Shannon and Simpson indices were not different. Exploratory taxonomic analyses identified treatment-associated differences in selected DSS-altered fecal taxa, including attenuation of Proteobacteria-related expansion. Thus, PAA administered during DSS exposure attenuated acute colitis and was accompanied by barrier-associated changes and endpoint fecal microbiota alterations.