Gut Microbiome

Sulfate Groups Modulate the Protective Effects of Laminaria japonica Fucoidan against High-Fat Diet-Induced Intestinal Mucus Layer Injury via Gut Microbiota Regulation and Metabolic Profiling.

TL;DR

Both native and desulfated Laminaria japonica fucoidan alleviated high-fat diet-induced colonic mucus-layer injury in mice, but the sulfated native fucoidan was more potent in lipid regulation, Fut2 upregulation, NLRP3 inhibition and gut microbiota modulation, indicating that sulfation is important for fucoidan's protective potency on the intestinal mucus layer.

Key Findings

Native fucoidan (Fud) and desulfated fucoidan (dsFud) differed markedly in sulfate content and were compared in a high-fat diet mouse model of colonic mucus-layer injury.

  • Fud had a sulfate content of 26.6%, whereas dsFud had a sulfate content of 2.2%.
  • Both were tested in a high-fat diet-induced colonic mucus-layer injury mouse model.
  • The study aimed to clarify the mechanisms by which sulfate groups contribute to fucoidan's protection of the intestinal mucus barrier.

Both Fud and dsFud mitigated high-fat diet-induced obesity-related outcomes.

  • Both interventions reduced weight gain and fat accumulation.
  • Both improved dyslipidemia.

Both Fud and dsFud improved mucus layer indicators and reduced colonic inflammation.

  • Both increased the neutral/acidic mucin ratio and upregulated Muc2 expression.
  • Both alleviated colon inflammation and NLRP3 inflammasome activation.

Fud outperformed dsFud in hepatic lipid regulation and serum triglyceride reduction.

  • Compared with dsFud, Fud showed better hepatic lipid regulation.
  • Fud also produced a greater reduction in serum triglycerides.

Fud upregulated Fut2 more significantly and inhibited NLRP3 signaling more potently than dsFud.

  • Fut2 upregulation was more significant with Fud than with dsFud.
  • NLRP3 signaling was more potently inhibited by Fud.

Fud markedly altered gut microbiota composition, lowering the Firmicutes/Bacteroidota ratio and enriching specific genera.

  • Fud markedly reduced the Firmicutes/Bacteroidota ratio.
  • Fud enriched Parabacteroides, Desulfovibrio, and Akkermansia.

Both fucoidans suppressed primary bile acid metabolism and activated the aryl hydrocarbon receptor, per metabolomic profiling.

  • Metabolomic profiling showed both interventions suppressed primary bile acid metabolism.
  • Both activated the aryl hydrocarbon receptor (AhR).

Fud and dsFud engaged different amino acid metabolic pathways.

  • Fud activated tryptophan metabolism.
  • dsFud mainly enhanced arginine and proline metabolism.

Sulfation is important for the protective potency of fucoidan on the intestinal mucus layer.

  • Although desulfated fucoidan retained some protective effects, native sulfated fucoidan was more potent across several measures (lipid regulation, Fut2, NLRP3, microbiota).

What This Means

This study in mice looked at how a seaweed-derived compound called fucoidan, from Laminaria japonica (a kelp), protects the gut's mucus lining when animals eat a high-fat diet. The researchers compared regular fucoidan, which is rich in sulfate groups (26.6%), with a version in which most sulfate had been removed (2.2%), to see whether sulfate matters for the protective effect. Both versions reduced weight gain, fat buildup and abnormal blood lipids, improved markers of a healthier mucus layer (including more of the main mucus protein Muc2), and reduced gut inflammation. However, the regular sulfated fucoidan did better in several respects: it lowered liver fat and blood triglycerides more, boosted the gene Fut2 more, and dampened the inflammatory NLRP3 pathway more strongly. It also shifted gut bacteria toward a different makeup, including more Akkermansia, Parabacteroides and Desulfovibrio. The two versions also affected gut metabolism differently, with regular fucoidan activating tryptophan metabolism and the desulfated form mainly affecting arginine and proline metabolism. This research suggests that the sulfate groups on fucoidan help make it a more potent protector of the gut mucus barrier, which could inform how seaweed-based food ingredients are designed or selected. These results come from mice, so they do not by themselves show the same effects in people.

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Citation

Li H, Chen J, Zhang C, Cai W, Che H, Li H. (2026). Sulfate Groups Modulate the Protective Effects of Laminaria japonica Fucoidan against High-Fat Diet-Induced Intestinal Mucus Layer Injury via Gut Microbiota Regulation and Metabolic Profiling.. Journal of agricultural and food chemistry. https://doi.org/10.1021/acs.jafc.6c08201