Gut Microbiome

Two low molecular weight-polysaccharides isolated from the edible fungus Sarcodon imbricatus: Isolation, characterization, immunomodulatory and intestinal barrier-protective effects.

TL;DR

Two structurally distinct low molecular weight polysaccharides from Sarcodon imbricatus (SIP-1 and SIP-2) exhibit different biological profiles: SIP-1 primarily enhances intestinal barrier function and exerts anti-inflammatory effects, while SIP-2 acts as a pronounced immunomodulator, with both influencing gut microbiota composition.

Key Findings

SIP-1 is a 2.4 kDa heteropolysaccharide with a β-(1→6)-glucan backbone containing glucuronic acid-containing side chains, while SIP-2 is a 4.1 kDa branched β-(1→4)-glucan with terminal mannose residues.

  • The two polysaccharides were isolated from the edible fungus Sarcodon imbricatus and are structurally distinct from each other.
  • SIP-1 is characterized by a β-(1→6)-glucan backbone with glucuronic acid-containing side chains.
  • SIP-2 is a branched β-(1→4)-glucan notable for its terminal mannose residues.
  • Molecular weights are 2.4 kDa for SIP-1 and 4.1 kDa for SIP-2, both classified as low molecular weight polysaccharides.

SIP-1 significantly enhanced intestinal barrier function as demonstrated by increased transepithelial electrical resistance (TEER) and reduced fluorescently labeled dextran permeability.

  • Intestinal barrier function was assessed using TEER measurements and fluorescently labeled dextran permeability assays.
  • SIP-1 treatment increased transepithelial electrical resistance, indicating strengthened barrier integrity.
  • SIP-1 reduced fluorescently labeled dextran permeability, confirming reduced paracellular leakage.
  • SIP-2 showed limited barrier-protective properties compared to SIP-1 under the same experimental conditions.

SIP-1 exhibited anti-inflammatory effects both in vitro and in vivo by modulating pro-inflammatory cytokines.

  • SIP-1 demonstrated anti-inflammatory effects in both in vitro cell-based models and in vivo experimental conditions.
  • The anti-inflammatory mechanism involved modulation of pro-inflammatory cytokines.
  • These effects were observed under the specific experimental conditions examined in the study.

SIP-2 acted as a pronounced immunomodulator, enhancing immune responses in normal macrophages while reducing inflammation in lipopolysaccharide (LPS)-stimulated cells.

  • SIP-2 showed dual immunomodulatory behavior depending on the inflammatory status of the cells.
  • In normal macrophages, SIP-2 enhanced immune responses.
  • In LPS-stimulated macrophages, SIP-2 reduced inflammation.
  • This bidirectional immunomodulatory activity contrasts with SIP-1's primarily barrier-protective and anti-inflammatory profile.

SIP-1 administration was associated with enrichment of beneficial gut microbes from the family Muribaculaceae, while SIP-2 was associated with increased abundance of immune-regulating bacteria Blautia and Akkermansia.

  • The two polysaccharides differentially modulated gut microbiota composition.
  • SIP-1 enriched beneficial gut microbes including Muribaculaceae.
  • SIP-2 administration was associated with increased abundance of Blautia and Akkermansia, bacteria associated with immune regulation.
  • The distinct microbiota modulation patterns align with the different biological activities observed for each polysaccharide.

Variations in glycosidic linkage type and terminal sugar residues between the two polysaccharides corresponded to distinct biological profiles in gut barrier function, immune responses, and microbiota modulation.

  • SIP-1 with β-(1→6) linkages and glucuronic acid side chains was associated with barrier-protective and anti-inflammatory activities.
  • SIP-2 with β-(1→4) linkages and terminal mannose residues was associated with immunomodulatory activities.
  • The authors conclude that variations in composition and linkage patterns in fungal polysaccharides may relate to different effects on gut barrier function, immune responses, and microbiota.
  • The findings highlight the potential relevance of these polysaccharides for gut health and immune modulation.

What This Means

This research investigates two sugar-chain molecules (polysaccharides) extracted from the edible mushroom Sarcodon imbricatus, called SIP-1 and SIP-2. Despite both coming from the same mushroom, these molecules have different chemical structures — they differ in how their sugar units are linked together and what types of sugars are at the ends of their chains. The researchers found that these structural differences lead to very different effects in the body when tested in laboratory and animal models. SIP-1 was particularly good at strengthening the intestinal barrier — the protective lining of the gut that prevents harmful substances from passing into the bloodstream — and at reducing inflammation. SIP-1 also promoted the growth of beneficial gut bacteria from the Muribaculaceae family. SIP-2, on the other hand, was a stronger immune system modulator: it could boost immune activity in normal immune cells while calming excessive inflammation in cells that had been stimulated with a bacterial trigger. SIP-2 also promoted the growth of gut bacteria associated with immune regulation, specifically Blautia and Akkermansia. This research suggests that even small differences in the chemical structure of mushroom-derived polysaccharides can lead to meaningfully different biological effects. This finding is relevant for understanding how dietary fungi might support gut health and immune function, and could help guide efforts to develop specific mushroom-derived compounds for targeted health applications. The work adds to growing evidence that the structural details of polysaccharides — not just their source — matter for their biological activity.

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Citation

Lo T, Zheng X, Chen K, He J, Yang X, Shen Y, et al.. (2026). Two low molecular weight-polysaccharides isolated from the edible fungus Sarcodon imbricatus: Isolation, characterization, immunomodulatory and intestinal barrier-protective effects.. Carbohydrate polymers. https://doi.org/10.1016/j.carbpol.2026.125161