Phellinus linteus polysaccharides alleviate DSS-induced colitis in mice by restoring gut microbiota homeostasis, preserving intestinal barrier integrity, and attenuating JAK2/STAT3-associated inflammatory signaling

This study examines whether polysaccharides extracted from Phellinus linteus — a medicinal mushroom long used in East Asian traditional medicine — can reduce intestinal inflammation in a standard mouse model of colitis. Researchers induced colitis in mice using dextran sodium sulfate (DSS), then treated them with these fungal polysaccharides to assess therapeutic effects. The study tracked three interlinked mechanisms: changes in the gut microbial community, preservation of the physical barrier lining the intestine, and suppression of a specific inflammatory signaling cascade (JAK2/STAT3). The key finding is that Phellinus linteus polysaccharides appear to work on all three fronts simultaneously — rebalancing disrupted microbiota, reinforcing tight-junction proteins that keep the gut lining intact, and dampening the JAK2/STAT3 pathway that drives chronic intestinal inflammation. This is significant because ulcerative colitis and related inflammatory bowel diseases remain difficult to treat, and plant- or fungal-derived polysaccharides represent a potentially lower-toxicity adjunct or alternative to immunosuppressive drugs. The study adds to a growing body of evidence that bioactive carbohydrates from natural sources can engage the gut-immune axis at multiple levels. However, as a preprint mouse study, the findings require independent replication and human clinical validation before any therapeutic implications can be drawn.

• Phellinus linteus polysaccharide treatment significantly reduced DSS-induced colitis severity in mice, as measured by disease activity index, colon length recovery, and histopathological scoring of colonic tissue.
• Treatment restored gut microbiota homeostasis, with reported shifts in microbial community composition including increases in beneficial taxa and reductions in pro-inflammatory species associated with DSS-induced dysbiosis.
• Intestinal barrier integrity was preserved, evidenced by upregulated expression of tight-junction proteins (including occludin and claudin family members), and inflammatory signaling through the JAK2/STAT3 pathway was attenuated, with reduced phosphorylation of JAK2 and STAT3 alongside lower levels of downstream pro-inflammatory cytokines such as IL-6 and TNF-α.

The study used a DSS-induced acute colitis mouse model, a well-established preclinical system for mimicking key features of human ulcerative colitis. Mice received oral administration of Phellinus linteus polysaccharides at defined doses (specific dose ranges as reported in the study) over the course of the DSS challenge period. Outcomes were assessed through a combination of microbiota profiling (likely 16S rRNA sequencing), intestinal permeability assays, immunohistochemistry, Western blotting for tight-junction and signaling proteins, and cytokine quantification. This is a preprint and full methodological details, including exact group sizes and dosing schedules, should be verified against the final published version.

As an animal preprint study, findings cannot be directly extrapolated to human IBD patients, and clinical trials would be required to establish safety, effective dosing, and therapeutic efficacy in people. The DSS model replicates acute mucosal inflammation but does not fully capture the chronic, relapsing-remitting nature of human Crohn's disease or ulcerative colitis. The causal directionality between microbiota changes and downstream barrier/signaling improvements is not fully resolved — it remains unclear whether microbiota restoration drives barrier repair or vice versa, and whether JAK2/STAT3 inhibition is a primary or secondary effect. Future experiments using germ-free or antibiotic-depleted mice would help disentangle the microbiota-dependent versus direct epithelial effects of the polysaccharides.

This study extends [§118], which similarly demonstrates that a plant-derived polysaccharide (mannan from Scilla scilloides) ameliorates DSS colitis via microbiota modulation and anti-inflammatory activity, reinforcing the broader principle that structurally diverse natural polysaccharides converge on overlapping gut-immune mechanisms. It parallels [§120], where a gut commensal (Eubacterium rectale) mitigates IBD through metabolic and signaling interventions, suggesting that both exogenous polysaccharides and endogenous microbial members may target similar mucosal homeostasis pathways. The finding that barrier protein expression is restored also parallels [§155], which examines how Saccharomyces boulardii supports intestinal barrier function, highlighting a shared therapeutic endpoint across phylogenetically distant biological agents. The JAK2/STAT3 signaling focus complements [§119], which targets a different inflammatory node (ZBP1-driven pyroptosis) in ulcerative colitis, together illustrating that multiple upstream pathways converge on mucosal destruction and represent distinct pharmacological targets. Collectively, this article situates Phellinus linteus polysaccharides within an expanding corpus of natural-product and microbiome-based strategies for IBD that operate through tri-axial mechanisms of microbiota rebalancing, barrier reinforcement, and immune signaling suppression.

• Anti-inflammatory and gut microbiota-modulating effects of a novel mannan from Scilla scilloides on DSS-induced colitis in mice
  Direct mechanistic parallel: both test a natural polysaccharide in a DSS-colitis mouse model and assess microbiota modulation plus anti-inflammatory effects, making side-by-side comparison of structural and functional polysaccharide differences informative.
• Eubacterium rectale Mitigates Inflammatory Bowel Disease via Modulation of Glutamine Metabolism Through the GLS2 and NF-κB Pathway
  Complementary microbiota-centric approach: where this study uses an exogenous fungal polysaccharide to reshape the microbiome, Eubacterium rectale acts as a commensal mediator — comparing outcomes illuminates whether microbial restoration or direct supplementation is the more proximal driver of barrier repair.
• Emapunil attenuates ulcerative colitis by suppressing Z-DNA binding protein 1 driven pyroptosis and pro-inflammatory polarization in macrophages
  Distinct signaling target in the same disease context: Emapunil addresses ZBP1-pyroptosis while this study targets JAK2/STAT3 — comparing the two clarifies whether blocking different inflammatory nodes yields additive, redundant, or divergent mucosal protection.
• Saccharomyces Boulardii CNCM I-745 on Intestinal Barrier Function
  Shared barrier-integrity endpoint: Saccharomyces boulardii's effects on tight-junction proteins and intestinal permeability directly mirror the barrier findings here, allowing readers to benchmark fungal polysaccharide efficacy against a better-characterized probiotic intervention.
• Intermittent fasting alleviates ulcerative colitis via lithocholic acid-mediated macrophage reprogramming
  Alternative upstream intervention: intermittent fasting alleviates ulcerative colitis via bile acid-mediated macrophage reprogramming rather than polysaccharide supplementation, offering a contrasting mechanistic entry point into the same gut-immune axis.