College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, P. R. China.
Jilin Provincial Key Laboratory of Grassland Farming, Key Laboratory of Mollisols Agroecology, Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Changchun 130102, P. R. China.
J Agric Food Chem. 2023 May 31;71(21):8164-8181. doi: 10.1021/acs.jafc.2c08076. Epub 2023 May 18.
Deoxynivalenol (DON) is a widespread mycotoxin and causes anorexia and emesis in humans and animals; GG (LGG), a well-characterized probiotic, can improve intestinal barrier function and modulate immune response. Currently, it is unclear whether LGG has a beneficial effect on DON-induced anorexia. In the present study, mice were treated with DON, LGG, or both by gavage for 28 days to evaluate the effects of LGG on DON-induced anorexia. Antibiotic treatment and fecal microbiota transplant (FMT) experiment were also conducted to investigate the link between DON, LGG, and gut microbiota. LGG significantly increased the villus height and reduced the crypt depth in jejunum and ileum, enhanced the tight junction proteins expression in the intestine, and regulated the TLR4/NF-κB signaling pathway, consequently attenuating the intestinal inflammation caused by DON. In addition, LGG increased the relative abundance of and butyric acid production of cecal contents; remodeled phenylalanine metabolism and tryptophan metabolism; reduced plasma peptide tyrosine tyrosine (PYY), 5-hydroxytryptamine (5-HT), and glucagon-like peptide-1 (GLP-1) concentrations; and promoted hypothalamic NPY and AgPR gene expression, which will further promote food intake and reduce weight loss, ultimately alleviating DON-induced anorexia in mice. Interestingly, antibiotic treatment diminished the intestinal toxicity of DON. The FMT experiment showed that DON-originated microbiota promotes intestinal inflammation and anorexia, while LGG + DON-originated microbiota has no adverse effects on mice. Both antibiotic treatment and FMT experiment have proved that gut microbiota was the primary vector for DON to exert its toxic effects and an essential mediator of LGG protection. In summary, our findings demonstrate that gut microbiota plays essential roles in DON-induced anorexia, and LGG can reduce the adverse effects caused by DON through its structure and regulate the gut microbiota, which may lay the important scientific foundation for future applications of LGG in food and feed products.
脱氧雪腐镰刀菌烯醇（DON）是一种广泛存在的真菌毒素，会引起人和动物的厌食和呕吐；长双歧杆菌（LGG）是一种经过充分研究的益生菌，可改善肠道屏障功能并调节免疫反应。目前，尚不清楚 LGG 是否对 DON 引起的厌食有有益作用。在本研究中，通过灌胃用 DON、LGG 或两者处理小鼠 28 天，以评估 LGG 对 DON 引起的厌食的影响。还进行了抗生素治疗和粪便微生物移植（FMT）实验，以研究 DON、LGG 和肠道微生物群之间的联系。LGG 显著增加了空肠和回肠的绒毛高度并降低了隐窝深度，增强了肠道中的紧密连接蛋白表达，并调节了 TLR4/NF-κB 信号通路，从而减轻了 DON 引起的肠道炎症。此外，LGG 增加了盲肠内容物中 和丁酸的相对丰度；重塑了苯丙氨酸代谢和色氨酸代谢；降低了血浆肽酪氨酸酪氨酸（PYY）、5-羟色胺（5-HT）和胰高血糖素样肽-1（GLP-1）的浓度；并促进了下丘脑 NPY 和 AgPR 基因的表达，这将进一步促进食物摄入并减少体重减轻，最终缓解了 DON 诱导的小鼠厌食。有趣的是，抗生素治疗减轻了 DON 的肠道毒性。FMT 实验表明，DON 起源的微生物群会促进肠道炎症和厌食，而 LGG+DON 起源的微生物群对小鼠没有不良影响。抗生素治疗和 FMT 实验均证明了肠道微生物群是 DON 发挥其毒性作用的主要载体，也是 LGG 保护的重要介质。总之，我们的研究结果表明，肠道微生物群在 DON 诱导的厌食中起着重要作用，LGG 可以通过其结构减少 DON 引起的不良反应并调节肠道微生物群，这可能为未来 LGG 在食品和饲料产品中的应用奠定重要的科学基础。
