Sun Runbin, Jin Dandan, Fei Fei, Xu Zhi, Cao Bei, Li Juan
Phase I Clinical Trials Unit, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China.
Front Pharmacol. 2023 Jun 7;14:1172963. doi: 10.3389/fphar.2023.1172963. eCollection 2023.
Polysaccharides from (Dicks.) Gray (HSH) and (Fr.) Pilat (BHR) showed noticeable effects on dextran sulfate sodium (DSS)-induced colitis, but their systemic modulation effects have not been fully revealed. This study aimed to investigate the regulation of the gut microbiota and systemic metabolism by HSH and BHR in DSS-induced colitis. C57BL/6J mice were given DSS (2.5%) in water and were treated with HSH and BHR (200 mg/kg/day) by gavage. Body weight and colon length were recorded, and H&E and AB-PAS staining of the colon were conducted to evaluate the model and the protective effect of the polysaccharides. Additionally, an LC-QTOF/MS-based untargeted metabolomic platform was used to identify the metabolites in the serum, colon tissue, gut contents, and faeces and investigate differential metabolites and metabolic pathways. 16S rDNA gene sequencing was used to measure the composition of bacterial communities. The results showed that the mouse colitis model was established successfully, as evidenced by an increased disease activity index score [2.83 ± 0.62 vs. 0.06 ± 0.14 ( < 0.001)] and shortened colon length [5.43 ± 0.64 cm vs. 7.04 ± 0.29 cm ( < 0.001)], and HSH and BHR ameliorated DSS-induced colitis by improving the disease activity index (2.17 ± 0.28 and 1.83 ± 0.29, respectively) and restoring the colon length (6.12 ± 0.30 cm and 6.62 ± 0.35 cm, respectively). HSH and BHR significantly modulated metabolites involved in aromatic amino acid metabolism, the citrate cycle, purine metabolism, pyrimidine metabolism, etc. HSH and BHR increased the Chao1 index by 64.25% and 60.25%, respectively, and they increased the Shannon index by 13.02% and 10.23%, respectively. They both reversed the increase in the abundances of , , , and and reversed the decrease in the abundance of induced by DSS. Specifically, HSH reversed the reductions in and , and BHR reversed the decreases in and . These results suggested that HSH and BHR may ameliorate DSS-induced colitis by global modulation of systemic metabolism and the gut microbiota. Targeting the gut microbiota may be a potentially effective strategy to modulate systemic metabolism and treat colitis.
来自（Dicks.）Gray（HSH）和（Fr.）Pilat（BHR）的多糖对葡聚糖硫酸钠（DSS）诱导的结肠炎显示出显著作用，但其全身调节作用尚未完全揭示。本研究旨在探讨HSH和BHR对DSS诱导的结肠炎中肠道微生物群和全身代谢的调节作用。将C57BL/6J小鼠给予含2.5% DSS的水，并通过灌胃给予HSH和BHR（200 mg/kg/天）。记录体重和结肠长度，并对结肠进行苏木精-伊红（H&E）和阿尔辛蓝-过碘酸雪夫（AB-PAS）染色，以评估模型及多糖的保护作用。此外，使用基于液相色谱-四极杆飞行时间质谱（LC-QTOF/MS）的非靶向代谢组学平台来鉴定血清、结肠组织、肠道内容物和粪便中的代谢物，并研究差异代谢物和代谢途径。采用16S rDNA基因测序来测定细菌群落组成。结果表明，成功建立了小鼠结肠炎模型，疾病活动指数评分升高[分别为2.83±0.62 vs. 0.06±0.14（P<0.001）]和结肠长度缩短[分别为5.43±0.64 cm vs. 7.04±0.29 cm（P<0.001）]证明了这一点，且HSH和BHR通过改善疾病活动指数（分别为)2.17±0.28和1.83±0.29）和恢复结肠长度（分别为6.12±0.30 cm和6.62±0.35 cm）改善了DSS诱导的结肠炎。HSH和BHR显著调节了参与芳香族氨基酸代谢、柠檬酸循环、嘌呤代谢、嘧啶代谢等的代谢物。HSH和BHR分别使Chao1指数增加了64.25%和60.25%，使香农指数分别增加了13.02%和10.23%。它们都逆转了DSS诱导的、、、和丰度的增加以及丰度的降低。具体而言，HSH逆转了和的减少，BHR逆转了和的减少。这些结果表明，HSH和BHR可能通过对全身代谢和肠道微生物群的整体调节来改善DSS诱导的结肠炎。靶向肠道微生物群可能是调节全身代谢和治疗结肠炎的一种潜在有效策略。
