Pretreatment with Yeast-Derived Complex Dietary Polysaccharides Suppresses Gut Inflammation, Alters the Microbiota Composition, and Increases Immune Regulatory Short-Chain Fatty Acid Production in C57BL/6 Mice
Pretreatment with Yeast-Derived Complex Dietary Polysaccharides Suppresses Gut Inflammation, Alters the Microbiota Composition, and Increases Immune Regulatory Short-Chain Fatty Acid Production in C57BL/6 Mice
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DOI：
10.1093/jn/nxz328
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发表时间：
2020-05-01
影响因子：
4.2
通讯作者：
Vasu, Chenthamarakshan
中科院分区：
文献类型：
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作者：
Gudi, Radhika;Suber, Jada;Vasu, Chenthamarakshan
背景：β-葡聚糖（BG）是一组复杂的膳食多糖（CDP），可作为膳食补充剂。然而，口服高纯度BG对肠道炎症的影响在很大程度上是未知的。Objectives：本研究的目的是调查口服高纯度，酵母衍生的BG（YBG; β-1，3/1，6-D-葡聚糖）对结肠炎的易感性的影响。实验（Expt）1：每天用盐水（对照）或250 μ gYBG处理雄性和雌性小鼠40天，然后在第30-35天用2.5%（wt：vol）葡聚糖硫酸钠（DSS）的饮用水处理;测定结肠炎严重程度和肠免疫表型。实验2：用盐水或YBG处理雌性B6小鼠30天，并测定肠免疫表型、肠微生物群组成和粪便SCFA浓度。实验3：如实验2中那样处理雌性B6小鼠，在第16-30天期间给予含有或不含抗生素[Abx;氨苄青霉素（1g/L）、万古霉素（0.5g/L）、新霉素（1g/L）和甲硝唑（1g/L）]的饮用水，并测定肠道免疫表型和粪便SCFA浓度。实验4：雌性B6 Foxp 3-绿色荧光蛋白（-GFP）报道小鼠如实验3中那样处理，并测定肠T调节细胞（Treg）频率和免疫表型。实验五：结果：与对照组相比，实验1中的YBG组对结肠炎的症状表现有明显的抑制作用，如体重减轻，结肠炎的严重程度和肠道细胞因子的产生结肠缩短率（24%; P = 0.016）和组织病理学严重程度评分（45%; P = 0.01）。实验2的YBG组显示出肠道微生物群的丰度向拟杆菌属（16%; P = 0.049）和疣微菌属（平均值+/- SD：对照= 7.8 +/- 0.44对比YBG = 21.0 +/- 9.6%）转移，厚壁菌门减少（66%; P < 0.001）。YBG组还显示出显著更高浓度的粪便SCFA，如乙酸（37%; P = 0.016）、丙酸（47%; P = 0.026）和丁酸（57%; P = 0.013）。与对照组相比，实验2的YBG组在肠粘膜中显示出更高的TlR频率（32%; P = 0.043）。YBG组小鼠肠道微生物群的消耗导致粪便SCFA浓度（实验3）和肠道Treg频率（实验4）降低。与YBG组相比，实验5的YBG-（Abx）组显示出加重的结肠炎特征，包括体重减轻（>100%; P < 0.01）和结肠炎症评分（42%; P = 0.04）。结论：使用B6小鼠的研究表明，当肠道微生物群完整时，膳食BG有益于促进肠道健康。然而，如果肠道微生物群受损，这些CDP可能会产生不良影响。
Background: beta-Glucans (BGs), a group of complex dietary polysaccharides (CDPs), are available as dietary supplements. However, the effects of orally administered highly purified BGs on gut inflammation are largely unknown.Objectives: The aim of this study was to investigate the impact of orally administering highly purified, yeast-derived BG (YBG; beta-1,3/1,6-D-glucan) on susceptibility to colitis.Methods: Eight-week-old C57BL/6 (B6) mice were used in a series of experiments. Experiment (Expt) 1: male and female mice were treated every day, for 40 d, with saline (control) or 250 mu g YBG, followed by 2.5% (wt:vol) dextran sulfate sodium (DSS) in drinking water during days 30-35; and colitis severity and intestinal immune phenotype were determined. Expt 2: female B6 mice were treated with saline or YBG for 30 d and intestinal immune phenotype, gut microbiota composition, and fecal SCFA concentrations were determined. Expt 3: female B6 mice were treated as in Expt 2, given drinking water with or without antibiotics [Abx; ampicillin (1 g/L), vancomycin (0.5 g/L), neomycin (1 g/L), and metronidazole (1 g/L)] during days 16-30, and gut immune phenotype and fecal SCFA concentrations were determined. Expt 4: female B6 Foxp3-green fluorescent protein (-GFP) reporter mice were treated as in Expt 3, and intestinal T-regulatory cell (Treg) frequencies and immune phenotypes were determined. Expt 5: female mice were treated as in Expt 1, given drinking water with or without antibiotics during days 16-40, and colitis severity and intestinal cytokine production were determined.Results: Compared with controls, the YBG group in Expt 1 exhibited suppressive effects on features of colitis, such as loss of body weight (by 47%; P < 0.001), shortening of colon (by 24%; P = 0.016), and histopathology severity score (by 45%; P = 0.01). The YBG group of Expt 2 showed a shift in the abundance of gut microbiota towards Bacteroides (by 16%; P = 0.049) and Verrucomicrobia (mean +/- SD: control = 7.8 +/- 0.44 vs. YBG = 21.0 +/- 9.6%) and a reduction in Firmicutes (by 66%; P < 0.001). The YBG group also showed significantly higher concentrations of fecal SCFAs such as acetic (by 37%; P = 0.016), propionic (by 47%; P = 0.026), and butyric (by 57%; P = 0.013) acids. Compared with controls, the YBG group of Expt 2 showed higher frequencies of Tregs (by 32%; P = 0.043) in the gut mucosa. Depletion of gut microbiota in the YBG group of mice caused diminished fecal SCFA concentrations (Expt 3) and intestinal Treg frequencies (Expt 4). Compared with the YBG group, the YBG-(Abx) group of Expt 5 showed aggravated colitis features including loss of body weight (by >100%; P < 0.01) and colonic inflammation score (by 42%; P = 0.04).Conclusions: Studies using B6 mice show that dietary BGs are beneficial for promoting intestinal health when the gut microbiota is intact. However, these CDPs may produce adverse effects if gut microbiota is compromised.