Microbiome–Metabolomics Analysis Reveals the Mechanism of Holothuria leucospilota Polysaccharides (HLP) in Ulcerative Colitis

Abstract

Scope: Holothuria leucospilota polysaccharides (HLP) are bioactive polysaccharides with immunomodulatory effects. This study aims to investigate the impact of HLP on dextran sodium sulfate (DSS)-induced colitis in rats and further investigate the complex interactions between changes in intestinal microbiota, cometabolites, and intestinal inflammation under HLP intervention. Methods and results: The ulcerative colitis (UC) model of Sprague Dawley (SD) rats is established by a normal diet with 3%DSS. The effects of HLP on UC are studied by gavage of different doses of HLP for 2 weeks. The results show that HLP alleviate the inflammation of UC and reduce histological damage and secretion of tumor necrosis factor-𝜶 (TNF-𝜶), IL-6, IL-1𝜷, and IL-10. After HLP treatment, the intestinal flora of UC rats is regulated, and the flora diversity is restored. Fecal metabolomics analysis reveal the modulatory effects of HLP on amino acid metabolism, antimicrobial peptide anabolism, and energy metabolism in rats with colitis. Correlation analysis of microbial and intestinal metabolites reveals the potential mechanism of HLP affecting colitis. Conclusion: HLP repair the intestinal compartment's metabolic disorder by regulating intestinal flora's structure and alleviating colonic mucosal injury and inflammation in colitis rats.

Microbiome–Metabolomic Analysis Revealed the Immunoprotective Effects of the Extract of Vanilla planifolia Andrew (EVPA) on Immunosuppressed Mice

“…The chromatographic column used was a Waters ACQUITY UPLC HSS T3 C18 (2.1 mm × 100 mm, 1.8 µm). The gradient elution program and mass spectrometry acquisition conditions were as previously described [ 22 ].…”

Holothuria leucospilota polysaccharides (HLP) ameliorate colitis rats via regulation of the metabolic profiling and TLR4/NLRP3 signaling pathways

“…The mixture was centrifuged (4 • C, 2240 × g) for 20 min, and the supernatant was filtered through a 0.22 μm filter membrane and then transferred into the sample bottle. The detailed UPLC-Q-TOF-MS methods referred to the previous study (Zhang et al, 2023).…”

“…H. leucospilota polysaccharides (HLP) are one of the important active substances in the sea cucumber. Published data have suggested that HLP consisted of three main monosaccharides: D-glucuronic acid, N-acetylgalactosamine, and fucose in the different mole ratios of 0.45:1.00:2.40 (Zhang et al, 2023). HLP have various biological activities, such as antiobesity, antioxidant, antidiabetic, relieving constipation, and immunomodulatory (Wang et al, 2021;Yuan et al, 2019;Zhao et al, 2020).…”

“…HLP have various biological activities, such as antiobesity, antioxidant, antidiabetic, relieving constipation, and immunomodulatory (Wang et al, 2021;Yuan et al, 2019;Zhao et al, 2020). Studies have shown that HLP regulated gut microbiota by fermentation in the gut (Zhang et al, 2023). Therefore, the metabolic and immune mechanisms of HLP in preventing and alleviating colitis were further explored.…”

“…After centrifugation at 3500 g for 15 min, the precipitate was dissolved in distilled water and dialyzed for 3 days. The crude HLP was obtained by freeze-drying for 48 h. The crude HLP was separated and purified using the previous method (Zhang et al, 2023).…”