氟苯尼考诱导的肠道微生物群失调损害蛋鸡的肠道稳态和宿主免疫系统。

Florfenicol-induced dysbiosis impairs intestinal homeostasis and host immune system in laying hens.

作者信息

Yu Keesun, Choi Inhwan, Kim Minseong, Pyung Young Jin, Lee Jin-Sun, Choi Youbin, Won Sohyoung, Kim Younghoon, Park Byung-Chul, Han Seung Hyun, Park Tae Sub, Dalgaard Tina Sørensen, Yun Cheol-Heui

机构信息

Department of Agricultural Biotechnology, and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, 08826, Republic of Korea.

Department of Oral Microbiology and Immunology, and Dental Research Institute, School of Dentistry, Seoul National University, Seoul, 08826, Republic of Korea.

出版信息

J Anim Sci Biotechnol. 2025 Apr 14;16(1):56. doi: 10.1186/s40104-025-01186-w.

Abstract

BACKGROUND

Despite growing concerns about the adverse effects of antibiotics in farm animals, there has been little investigation of the effects of florfenicol in laying hens. This study examined the effect of florfenicol on the intestinal homeostasis, immune system, and pathogen susceptibility of laying hens.

RESULTS

The oral administration of florfenicol at field-relevant levels for 5 d resulted in a decrease in the gut microbiota genera Lactobacillus, Bacillus, and Bacteroides, indicating the development of intestinal dysbiosis. The dysbiosis led to decreased mRNA levels of key regulators peroxisome proliferator-activated receptor gamma (PPAR-γ) and hypoxia-inducible factor-1α (HIF-1α), compromising intestinal hypoxia. Intestinal homeostasis was also disrupted, with decreased expression of Occludin and Mucin 2 (Muc2) genes combined with increased gut epithelial permeability. The breakdown in intestinal homeostasis and immune function provided a favorable environment for opportunistic bacteria like avian pathogenic Escherichia coli (APEC), culminating in systemic infection. Immunologically, florfenicol treatment resulted in increased proportion and absolute number of MRC1L-B monocytes/macrophages in the spleen, indicating an exacerbated infection. Furthermore, both the proportion and absolute number of γδ T cells in the lamina propria of the cecum decreased. Treatment with florfenicol reduced butyrate levels in the cecum. However, the administration of butyrate before and during florfenicol treatment restored factors associated with intestinal homeostasis, including PPAR-γ, Occludin, and Muc2, while partially restoring HIF-1α, normalized intestinal hypoxia and gut permeability, and reversed immune cell changes, suppressing APEC systemic infection.

CONCLUSION

The uncontrolled and widespread use of florfenicol can negatively affect intestinal health in chickens. Specifically, florfenicol was found to impair intestinal homeostasis and immune function in laying hens, including by reducing butyrate levels, thereby increasing their susceptibility to systemic APEC infection. The development of strategies for mitigating the adverse effects of florfenicol on gut health and pathogen susceptibility in laying hens is therefore essential.

摘要

背景

尽管人们越来越关注抗生素对农场动物的不良影响,但关于氟苯尼考对蛋鸡影响的研究却很少。本研究考察了氟苯尼考对蛋鸡肠道稳态、免疫系统和病原体易感性的影响。

结果

以与实际生产相关的剂量口服氟苯尼考5天,导致肠道微生物群中乳酸杆菌属、芽孢杆菌属和拟杆菌属减少,表明肠道出现了生态失调。这种失调导致关键调节因子过氧化物酶体增殖物激活受体γ(PPAR-γ)和缺氧诱导因子-1α(HIF-1α)的mRNA水平降低,损害了肠道缺氧状态。肠道稳态也受到破坏,紧密连接蛋白和黏蛋白2(Muc2)基因的表达降低,同时肠道上皮通透性增加。肠道稳态和免疫功能的破坏为禽致病性大肠杆菌(APEC)等机会性细菌提供了有利环境,最终导致全身感染。在免疫方面,氟苯尼考处理导致脾脏中MRC1L-B单核细胞/巨噬细胞的比例和绝对数量增加,表明感染加剧。此外,盲肠固有层中γδT细胞的比例和绝对数量均下降。氟苯尼考处理降低了盲肠中的丁酸盐水平。然而,在氟苯尼考处理之前和期间给予丁酸盐可恢复与肠道稳态相关的因子,包括PPAR-γ、紧密连接蛋白和Muc2,同时部分恢复HIF-1α,使肠道缺氧和肠道通透性正常化,并逆转免疫细胞变化,抑制APEC全身感染。

结论

氟苯尼考的无节制广泛使用会对鸡的肠道健康产生负面影响。具体而言,发现氟苯尼考会损害蛋鸡的肠道稳态和免疫功能,包括通过降低丁酸盐水平,从而增加它们对APEC全身感染的易感性。因此,制定减轻氟苯尼考对蛋鸡肠道健康和病原体易感性不良影响的策略至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a40/11995664/8aff549bdb71/40104_2025_1186_Fig1_HTML.jpg

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