藻寡糖增强肠道微生物群和肠道屏障功能，缓解脱氧雪腐镰刀菌烯醇诱导的宿主损伤。

Alginate Oligosaccharides Enhance Gut Microbiota and Intestinal Barrier Function, Alleviating Host Damage Induced by Deoxynivalenol in Mice.

机构信息

State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China; Feed Safety and Healthy Livestock, Beijing Jingwa Agricultural Innovation Center, Beijing, China; College of Animal Science and Veterinary Medicine, Jinzhou Medical University, Jinzhou, Liaoning, China.

出版信息

J Nutr. 2024 Nov;154(11):3190-3202. doi: 10.1016/j.tjnut.2024.09.031. Epub 2024 Sep 30.

DOI:10.1016/j.tjnut.2024.09.031

PMID:39357672

Abstract

BACKGROUND

Alginate oligosaccharides (AOS) exhibits notable effects in terms of anti-inflammatory, antibacterial, and antioxidant properties. Deoxynivalenol (DON) has the potential to trigger intestinal inflammation by upregulating pro-inflammatory cytokines and apoptosis, thereby compromising the integrity of the intestinal barrier function and perturbing the balance of the gut microbiota.

OBJECTIVES

We assessed the impact of AOS on mitigating DON-induced intestinal damage and systemic inflammation in mice.

METHODS

After a 1-wk acclimatization period, the mice were divided into 4 groups. For 3 wk, the AOS and AOS + DON groups were gavaged daily with 200 μL of AOS [200 mg/kg body weight (BW)], whereas the CON and DON groups received an equivalent volume of sterile Phosphate-Buffered Saline (PBS). Subsequently, for 1 wk, the DON and AOS + DON groups received 100 μL of DON (4.8 mg/kg BW) daily, whereas the control (CON) and AOS groups continued receiving PBS.

RESULTS

After administering DON via gavage to mice, there was a significant decrease (P < 0.05) in body weights compared with the CON group. Interestingly, AOS exhibited a tendency to mitigate this weight loss in the AOS + DON group. In the feces of mice treated with both AOS and DON, the concentration of DON significantly increased (P < 0.05) compared with the DON group alone. Histological analysis revealed that DON exposure caused increased intestinal damage, including shortened villi and eroded epithelial cells, which was ameliorated by presupplementation with AOS, alleviating harm to the intestinal barrier function. In both jejunum and colon tissues, DON exposure significantly reduced (P < 0.05) the expression of tight junction proteins (claudin and occludin in the colon) and the mucin protein mucin 2, compared with the CON group. Prophylactic administration of AOS alleviated these reductions, thereby improving the expression levels of these key proteins. Additionally, AOS supplementation protected DON-exposed mice by increasing the abundance of probiotics such as Bifidobacterium, Faecalibaculum, and Romboutsia. These gut microbes are known to enhance (P < 0.05) anti-inflammatory responses and the production of short-chain fatty acids (SCFAs), including total SCFAs, acetate, and valerate, compared with the DON group.

CONCLUSIONS

This study unveils that AOS not only enhances gut microbiota and intestinal barrier function but also significantly mitigates DON-induced intestinal damage.

摘要

背景

藻酸盐寡糖（AOS）具有显著的抗炎、抗菌和抗氧化特性。脱氧雪腐镰刀菌烯醇（DON）通过上调促炎细胞因子和细胞凋亡，引发肠道炎症，从而损害肠道屏障功能的完整性并扰乱肠道微生物群落的平衡。

目的

评估 AOS 对减轻 DON 诱导的小鼠肠道损伤和全身炎症的影响。

方法

经过 1 周的适应期后，将小鼠分为 4 组。在 3 周的时间里，AOS 和 AOS+DON 组每天通过灌胃给予 200 μL AOS（200 mg/kg 体重），而 CON 和 DON 组给予等量的无菌磷酸盐缓冲液（PBS）。随后，在 1 周的时间里，DON 和 AOS+DON 组每天接受 100 μL DON（4.8 mg/kg BW），而对照（CON）和 AOS 组继续接受 PBS。

结果

给予 DON 后，与 CON 组相比，小鼠体重明显下降（P<0.05）。有趣的是，AOS 表现出减轻 AOS+DON 组体重减轻的趋势。在同时给予 AOS 和 DON 的小鼠粪便中，DON 的浓度与单独给予 DON 的组相比显著增加（P<0.05）。组织学分析表明，DON 暴露导致肠道损伤增加，包括绒毛缩短和上皮细胞侵蚀，这一损伤通过预先给予 AOS 得到改善，减轻了对肠道屏障功能的损害。在空肠和结肠组织中，与 CON 组相比，DON 暴露显著降低了（P<0.05）紧密连接蛋白（结肠中的 Claudin 和 Occludin）和粘蛋白蛋白 2 的表达。预防性给予 AOS 缓解了这些降低，从而提高了这些关键蛋白的表达水平。此外，AOS 补充通过增加双歧杆菌、粪杆菌和罗姆斯氏菌等益生菌的丰度来保护 DON 暴露的小鼠。与 DON 组相比，这些肠道微生物可增强（P<0.05）抗炎反应和短链脂肪酸（SCFAs）的产生，包括总 SCFAs、乙酸盐和缬酸盐。