南昌大学熊涛教授团队：鼠李糖乳杆菌NCUH061012通过调节肠道微生物和代谢物来缓解高尿酸血症

近日，南昌大学食品科学与资源挖掘全国重点实验室Xueting Zhao(第一作者)、熊涛教授(通讯作者)等在国际食品期刊《Food Bioscience》发表了题为“Lacticaseibacillus rhamnosus NCUH061012 alleviates hyperuricemia via modulating gut microbiota and intestinal metabolites in mice”的研究论文。

高尿酸血症 (HUA)作为一种严重的代谢疾病，药物治疗常常具有副作用，迫切需要安全且有效策略来预防和治疗HUA。最近研究发现乳酸菌(LAB)可能具有缓解HUA的潜力，但是具有抗HUA作用的LAB仍然稀少。而且，缓解HUA机制复杂且不清楚，因此，值得寻找各种抗HUA的LAB并探究其缓解机制。

在该研究中，研究人员通过从婴儿粪便中分离、体外筛选和在小鼠中评估来获得具有抗HUA潜力的鼠李糖乳杆菌NCUH061012(LR012)，并首次整合粪便微生物组和代谢物组来揭示LAB减轻HUA潜在机制。研究发现，LR012补充能够有效降低尿酸(UA)水平，相比HUA模型组，LR012补充能够降低血清尿酸(SUA)37.20%。LR012促进Lactobacillus和Candidatus_Saccharimonas的生长，降低Bacteroides丰度，增加短链脂肪酸水平和降低脂多糖水平。粪便代谢组学分析显示LR012调节更多的肠道代谢物包括腺苷、次黄嘌呤、黄嘌呤、琥珀酸和色氨酸。而且，肠道微生物和代谢物的这些变化与改善的系统炎症和肾损伤、调节UA生成和排泄以及降低的SUA水平正相关。研究人员推断LR012在缓解HUA的潜在机制是调节肠道微生物和代谢物。

Fig. 1. Evaluation and identification of isolates with anti-HUA potential. (A) inhibition rate of XO, (B) survival rate in different conditions, (C) adhesion rate to Caco-2 cell, (D) phylogenetic tree of S7 and related bacteria. Data were expressed as mean ± SD (n = 3). Different letters on the graph indicated a significant difference (p < 0.05) between groups.

Fig. 2. Effects of LR in HUA mice. (A) SUA, (B) TNF-α, (C) IL-1β, (D) BUN, (E) CRE levels in serum, (F) XO activity in the liver and (G) Histological assessment of kidney tissue. Data were expressed as mean ± SD (n = 6). Different letters on the graph indicated a significant difference (p < 0.05) between groups.Fig. 3. Modulation of LR on the protein expression levels of UA transporters in HUA mice. (A) Images and expression of (B) URAT1, (C) GLUT9, (D) OAT1 and (E) ABCG2. Data were expressed as mean ± SD (n = 4). Different letters on the graph indicated a significant difference (p < 0.05) between groups.Fig. 4. Regulation of LR on gut microbiota diversity of HUA mice. (A) Chao1 index, (B) Shannon index, the weighted unifrac distance (C) PCoA and (D) NMDS and (E) Venn diagram. Data were expressed as mean ± SD (n = 6). Different letters on the graph indicated a significant difference (p < 0.05) between groups.Fig. 5. Effects of LR on the gut microbiota composition in HUA mice. The relative abundance of (A) gut microbiota at the phylum level, (B) gut microbiota at the genus level, (C) Bacteroidetes, (D) Firmicutes, (E) Bacteroides, (F) Lactobacillus and (G) Candidatus_Saccharimonas, (H) the histogram of LDA score from LEfSe analysis, and (I)The taxonomic cladogram from LEfSe analysis. Data were expressed as mean ± SD (n = 6). Different letters on the graph indicated a significant difference (p < 0.05) between groups. LDA score >2 was used as a threshold value of characteristic taxon.Fig. 6. The levels of SFCAs in the feces and LPS in serum of HUA mice. The levels of (A) acetate, (B) propanoate, (C)butyrate (D) total SCFAs and (E) LPS. Data were expressed as mean ± SD (n = 6). Different letters on the graph indicated a significant difference (p < 0.05) between groups.Fig. 7. Effect of LR on fecal metabolomics in HUA mice. (A) PCA score plots among QC, NC, HM and LR groups in positive ion mode, (B) PCA score plots among QC, NC, HM, and LR groups in negative ion mode, (C) OPLS-DA score plots between NC and HM groups in positive ion mode, (D) OPLS-DA score plots between NC and HM groups in negative ion mode, (E) OPLS-DA score plots between HM and LR groups in positive ion mode, (F) OPLS-DA score plots between HM and LR groups in negative ion mode, (G) Heatmap of important significant metabolites among NC, HM and LR groups. (H) Summary plot for pathway analysis of NC/HM (1–12 metabolic pathway satisfies the conditions of p < 0.05 or impact value > 0.1), (I) Summary plot for pathway analysis of HM/LR (1–5 metabolic pathway satisfies the conditions of p < 0.05 or impact value > 0.1).Fig. 8. Superman's correlation heatmap between the top 50 genera in relative abundance and HUA-related biochemical indexes. The positive and negative correlations between the bacteria and indexes are represented by the red and blue circles, respectively, and significant correlations are denoted by *p < 0.05 and **p < 0.01. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)Fig. 9. The underlying mechanisms of LR012 alleviating HUA. The solid red line represents an up-regulation, while the solid blue line indicates a down-regulation. The red dashed line represents promotion or positive correlation, while the blue dashed line represents inhibition or negative correlation. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

https://doi.org/10.1016/j.fbio.2024.103699

通讯作者

通讯作者简介同

通讯作者简介 

熊涛，博士，二级教授，博士生导师。主要从事益生菌及大宗果蔬高值化利用研究。1992年9月在南昌大学参加工作；2006年12月任南昌大学食品学院教授，2015年9月任南昌大学食品学院副院长。现任南昌大学食品科学与资源挖掘全国重点实验室常务副主任。

在国内外核心期刊上发表学术论文160余篇，其中SCI收录68篇，高被引论文1篇。授权发明专利24项，其中国际发明专利2项。主持完成国家863计划等科研课题50多项。获国家科技进步二等奖、江西省技术发明一等奖、中国侨界贡献奖（创新成果）、中国产学研创新合作成果一等奖、江西省科学技术进步一等奖、中国食品科学技术学会科技创新奖一等奖、国家级教学成果奖二等奖、江西省教学成果一等奖、宝钢优秀教师奖等荣誉。

来源：食品放大镜