A Soluble (1→3),(1→6)-β-D-Glucan from Pholiota nameko Protects Against DSS-Induced Colitis by Attenuating Inflammation, Visceral Hypersensitivity, and Mucosal Damage

Ulcerative colitis (UC) is a chronic inflammatory bowel disease associated with diarrhea, hematochezia, abdominal pain and weight loss. This study evaluated a soluble (1→3),(1→6)-β-D-glucan isolated from Pholiota nameko (PN) in dextran sulfate sodium (DSS)-induced colitis. PN was obtained and characterized as previously described [1]. Female Swiss mice were divided into three separately housed groups (n=10): Control, DSS and DSS + PN 100 mg/kg. Colitis was induced with 5% DSS in drinking water, and PN (100 mg/kg) was administered orally, once a day. Body weight, disease activity index (DAI), colon length, visceral mechanical hypersensitivity, and nest-building behavior were evaluated. After euthanasia, blood and colons were collected for biochemical and histological analysis. All experiments were approved by the Ethics Committee for the Use of Animals of UFPR (1452). DSS caused a body weight loss of 13.6±0.8% on day 8, which was prevented in 100% by PN. DSS increased DAI, reaching a 8.4±0.7 score on day 8, and reduced colon length in 22% (control: 10.2±0.2 cm). PN reduced DAI in 48% and increased colon length in 33% when compared to DSS group. On day 8, DSS increased frequency of response of visceral sensitivity in 95, 98, 80, 76 and 70% for von Frey filaments of 0.008, 0.2, 0.07, 0.16, and 0.6 g, respectively (control: 4.0±2.7, 2.0±2.0, 20.0±7.3, 24.0±5.0, 30.0±5.4% frequency, respectively); PN reduced response frequency in 63%, 50%, and 36% for 0.008, 0.02, and 0.07 g filaments. DSS decreased nest-building scores in 55% (control: 3.8±0.2 score), whereas PN increased it in 88% when compared to DSS group. DSS increased inflammatory-cell infiltration in 818%, MPO in 153%, and IL-1β in 517% (control: 16.3±0.9 cells/field, 4.7±0.8 O.D./mg protein, 945±468 pg/mg protein, respectively). PN reduced these parameters in 58%, 61%, and 79% when compared to DSS group. DSS decreased GSH levels in 189% and CAT activity in 66% (control: 881.3±103.5 μg/g of tissue and (8±1)x10^-4 mmol/mL/min), while PN increased these parameters in 189% and 149%. DSS reduced mucosal thickness in 66%, PCNA in 83%, acid and neutral mucins in 91% and 92%, and MUC-2 in 81% (control: 199±10μm, 70.2±8.4 cells/field, 2227±53, 989±39 and 108.6±10.9 pixels/field); PN increased these parameters by 124%, 353%, 481%, 285%, and 199%. PN did not alter hepatic or renal serum markers. PN, a soluble, highly branched prebiotic glucan, attenuated inflammation and visceral hypersensitivity while preserving antioxidant defenses and mucosal barrier integrity, demonstrating therapeutic potential for intestinal health.

This work was supported by CAPES (Finance Code 001) and CNPq (Proc.308816/2023-4).