南昌大学谢明勇院士团队发表封面文章

近日，南昌大学食品科学与资源挖掘全国重点实验室谢明勇院士团队在国际期刊《Journal of Agricultural and Food Chemistry》（中国科学院一区，IF：5.7）发表了题为“Highland Barley β-Glucan Relieves Symptoms of Colitis via PPARα-Mediated Intestinal Stem Cell Proliferation”的封面文章。余永康为第一作者。谢明勇院士和周兴涛副教授为共同通讯作者。

研究背景

青稞富含青稞β-葡聚糖(HBG)，HBG 具有多种生物和药用活性，如抗氧化、抗菌和抗炎活性。我们之前的研究表明，HBG 可以促进肠上皮细胞（IECs）再生，以改善葡聚糖硫酸钠（DSS）引起的结肠炎小鼠的症状。然而，HBG 与微生物之间的联系仍然是一个谜。目前的证据表明，天然多糖通过宿主 - 微生物相互作用在调节肠道微生物丰度或产生多种生物活性物质方面起着关键作用。然后，通过增加肠道干细胞(ISCs) 的增殖来改善炎症性肠病症状。

肠上皮细胞通过建立化学和物理屏障将肠道微生物与免疫细胞分开，从而建立宿主与共生菌的互利关系。为了在执行这些功能的同时避免受损细胞的积累，肠道每 4 - 5 天就会不断淘汰老化的肠干细胞，并迅速再生隐窝绒毛结构，这是身体中最快的再生过程（人体每天需要产生 3 亿个肠上皮细胞来弥补损失）。因此，肠干细胞的自我更新和分化在促进肠道内稳态方面起着不可或缺的作用。值得注意的是，Lgr5 + 肠干细胞产生潘氏细胞，并在肠道隐窝内快速分裂产生瞬时祖细胞。然后，沿着绒毛，这些细胞分化成各种类型的肠细胞，包括肠内分泌细胞和杯状细胞，最终这些细胞发生凋亡并在靠近上部区域脱落。最近的研究表明，PPARα靶点在宿主 - 细菌感染期间修复肠道屏障功能。研究表明，PPARα 参与肠道损伤下肠干细胞的更新和重塑。PPAR 的缺乏对于肠干细胞扩增的损伤是不可逆的。

然而，很少有研究从肠干细胞增殖的角度探讨 β- 葡聚糖对肠道屏障功能的影响。因此，我们的研究旨在考察 HBG 对肠干细胞增殖的影响，并研究其可能的机制，以便为应用 HBG 改善肠上皮稳态提供一种新方法。

研究结果

研究发现，青稞 β- 葡聚糖（HBG）减轻了结肠炎小鼠的病理症状并促进了肠干细胞的增殖。值得注意的是，代谢组学研究表明，经HBG处理后，二十二碳六烯酸（DHA）显著增加。DHA 是PPARα的配体，而其可促进肠干细胞增殖。不出所料，HBG促进了结肠炎小鼠肠道中PPARα的表达和肠干细胞的增殖。进一步的实验证实，DHA显著促进了肠道类器官中PPARα的表达和肠干细胞的增殖。有趣的是，PPARα 抑制剂逆转了 DHA 对肠干细胞增殖的作用。总之，我们的数据表明，HBG 可能通过 DHA 加速 PPARα 介导的肠干细胞增殖。这为多糖在维持肠道稳态中的有效应用提供了新的见解。

图文赏析

图形摘要

Figure 1. HBG ameliorated symptoms of DSS-induced colitis mice. (A) Quantification of average weight on the 7th day. (B) Quantification of average DAI on day 7 after modeling. (C) Quantification of mice colon length with DSS-induced colitis. (D) Representative images of the H&E staining of the colon, with the scale bar of 100 μm. (E) Histological score of H&E staining. (F) Representative images of the AB-PAS staining of mice colon with DSS-induced colitis, with the scale bar of 100 μm. (G) Number of goblet cells in each crypt of the colon. (H) Representative images of the IF staining of ZO-1 (red) and DAPI (blue), with the scale bar of 20 μm. (I) Quantitation of the area of ZO-1 (%). Results were expressed as mean ± SD (n = 6). #P < 0.001; **P < 0.01; *P < 0.05 vs the DSS group.

Figure 2. HBG changed the composition of intestinal microbiota in DSS-induced colitis mice. (A) Venn diagram. (B) PCoA. (C) Heat map of intestinal microbiota composition at the genus level. (D) TOP 10 intestinal microbiota composition at the genus level. (E) LDA scores of the differentially abundant bacteria in DSS and HL groups (LDA > 3.5). (F) Significantly altered CAZy in DSS and HL groups. The results were expressed as mean ± SD (n = 3).

Figure 3. HBG altered metabolites of intestinal microbiota in DSS-induced colitis mice. (A) PCoA. (B) VIP significant metabolite. (C) Heat maps enriched representative metabolites in three groups. (D) KEGG pathway enrichment analysis in three groups. (E) Spearman correlation analysis between intestinal microbiota and metabolite. The results were expressed as mean ± SD (n = 6). #P < 0.001; **P < 0.01; *P < 0.05 vs the DSS group.

Figure 4. HBG improved ISC proliferation through PPARα in DSS-induced colitis mice. (A) Representative images of the IF staining of PPARα with the scale bar of 20 μm. (B) Quantitation of the positive aera of PPARα. (C) Representative images of the IHC staining of Lgr5 with the scale bar of 20 μm. (D) Quantitation of the number of Lgr5+ ISCs per crypt. (E) Representative images of the IHC staining of Ki67 with the scale bar of 100 μm. (F) Quantitation of the number of Ki67+ cells per crypt. The results were expressed as mean ± SD (n = 6). #P < 0.001; **P < 0.01; *P < 0.05 vs the DSS group.

Figure 5. DHA activated the PPARα signaling to promote ISC proliferation in mice intestinal organoids. (A) Representative images of the IF staining of PPARα with the scale bar of 50 μm. (B) Quantitation of the positive aera of PPARα. (C) Representative images of the IF staining of Lgr5 with the scale bar of 50 μm. (D) Quantitation of the positive aera of Lgr5. (E) Representative images of the IF staining of EDU with the scale bar of 100 μm. (F) Quantitation of the positive aera of EDU. (G) Representative images of the IF staining of Ki67 with the scale bar of 100 μm. (H) Quantitation of the number of Ki67+ cells per crypt. The results were expressed as mean ± SD (n = 3–6). #P < 0.001; **P < 0.01; *P < 0.05 vs the TNFα group.

Figure 6. PPARα directly promoted the expression of Lgr5+ ISCs in intestinal organoids. (A) Representative images of the IF staining of the colocalization of PPARα (red), Lgr5 (green), and DAPI (blue) in organoids. (B) Quantitation of the positive aera of Lgr5. (C) Quantitation of the positive aera of PPARα. The results were expressed as mean ± SD (n = 6). #P < 0.001; **P < 0.01; *P < 0.05 vs the TNFα group.

Figure 7. PPARα antagonism reversed the ability of DHA to promote ISC proliferation in mice intestinal organoids. (A) Representative images of the IF staining of PPARα with the scale bar of 50 μm. (B) Quantitation of the positive aera of PPARα. (C) Representative images of the IF staining of Lgr5 with the scale bar of 50 μm. (D) Quantitation of the positive aera of Lgr5. (E) Representative images of the IF staining of EDU with the scale bar of 50 μm. (F) Quantitation of the positive aera of EDU. (G) Representative images of the IF staining of Ki67 with the scale bar of 50 μm. (H) Quantitation of the number of Ki67+ cells per crypt. The results were expressed as mean ± SD (n = 6). #P < 0.001; **P < 0.01; *P < 0.05 vs the NC group.

Figure 8. HBG activated the Wnt/β-catenin pathway in DSS-induced colitis mice. (A) Representative images of the IF staining of β-catenin with the scale bar of 20 μm. (B) Ratio of nuclear translocation of β-catenin. (C) Representative images of the IF staining of TCF7 with the scale bar of 20 μm. (D) Quantitation of the positive aera of TCF7. The results were expressed as mean ± SD (n = 6). #P < 0.001; **P < 0.01; *P < 0.05 vs the DSS group.

Figure 9. DHA stimulated the Wnt/β-catenin pathway under inflammatory conditions in mice intestinal organoids. (A) Representative images of the IF staining of β-catenin with the scale bar of 100 μm. (B) Ratio of nuclear translocation of β-catenin. (C) Representative images of the IF staining of TCF7 with the scale bar of 50 μm. (D) Quantitation of the positive aera of TCF7. The results were expressed as mean ± SD (n = 6). #P < 0.001; **P < 0.01; *P < 0.05 vs the TNFα group.

Figure 10. Schematic of the promotion of ISC proliferation by HBG via PPARα.

原文链接

https://pubs.acs.org/doi/10.1021/acs.jafc.3c09535

通讯作者简介

谢明勇，南昌大学教授，党的二十大代表，中国工程院院士，国际食品科学院院士。德国波恩大学营养学博士，全国优秀博士学位论文指导教师，食品科学国家重点学科带头人；国务院学位委员会第六届、第七届学科评议组成员，第六届、第七届教育部科学技术委员会农林学部委员，中国食品科学技术学会副理事长。现任南昌大学食品科学与资源挖掘全国重点实验室主任。主要研究领域为食品营养科学与技术。

立足国际研究前沿和国家重大需求，长期从事食源性多糖与果蔬发酵研究，破解了食源性多糖结构解析与功能评价技术难题；突破果蔬发酵菌种筛选与菌剂制备关键技术瓶颈，建成国内首个果蔬发酵专用菌库；创制多糖和益生菌发酵果蔬系列营养健康产品，催生出全新的养胃食疗和果蔬发酵绿色制造产业。近年主持国家自然科学基金重点项目、国家重点研发计划课题等国家级课题10余项。以通讯作者发表SCI收录论文200余篇，出版著作3部；获国家发明专利授权50余件；获国家科技进步奖二等奖、国际食品亲水胶体基金会大奖、国家级教学成果奖二等奖、江西省科学技术特别贡献奖等10余项奖励。2012年获“全国优秀科技工作者”荣誉称号。2018–2023连续6年入选科睿唯安全球“高被引科学家”榜单。领衔的食品科学与工程教师团队入选第二批“全国高校黄大年式教师团队”，培养的学生入选多项国家级人才项目等。

周兴涛，南昌大学食品学院副教授，博导。主要从事药食同源功能分子的提取、生物合成、功效与机制研究，及其开发利用。主持国家自然科学基金2项、国家重点研发子课题1项，江西省自然基金重点项目等省部级项目4项；以骨干（前三）参与国家重点、重大项目3项。近3年以第1作者或通讯作者在中国科学院1区Top期刊《Journal of agricultural and food chemistry》、《Food Hydrocolloids》、《Carbohydrate Polymers》等杂志上发表SCI论文20余篇，其中ESI高被引文章2篇、封面文章6篇、影响因子大于10的6篇。

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来源：学习强国

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来源 | 食品学院

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