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低剂量小檗碱在断奶仔猪体内代谢,对肠道形态或肠道微生物群无重大影响。

A Low Dose of Berberine Is Metabolized in Weaned Piglets Without Major Changes to Gut Morphology or Gut Microbiota.

作者信息

Mouchtoglou Christina, Cherlet Marc, Dehau Tessa, Aluwe Marijke, Ducatelle Richard, Goossens Evy, Croubels Siska, Van Immerseel Filip

机构信息

Livestock Gut Health Team (LiGHT) Ghent, Department of Pathobiology, Pharmacology and Zoological Medicine, Faculty of Veterinary Medicine, Ghent University, 9820 Merelbeke, Belgium.

Laboratory of Pharmacology and Toxicology, Department of Pathobiology, Pharmacology and Zoological Medicine, Faculty of Veterinary Medicine, Ghent University, 9820 Merelbeke, Belgium.

出版信息

Animals (Basel). 2025 Aug 21;15(16):2450. doi: 10.3390/ani15162450.

DOI:10.3390/ani15162450
PMID:40867778
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12383199/
Abstract

Weaning is one of the most challenging stages in a piglet's life, with multiple stressors contributing to poor gut health. For several years, zinc oxide (ZnO) was the preferred means of promoting a healthy gut and preventing post-weaning diarrhea (PWD). However, with the banning of its use at medicinal levels in the EU since 2022, alternatives are needed. Berberine (BBR), an isoquinoline alkaloid, has been used for centuries in Chinese medicine to treat diarrhea and has pharmacological properties that could make this molecule an attractive alternative to ZnO. The aim of this study was to investigate how berberine is metabolized in the intestinal tract and liver of weaned piglets; determine which metabolites are detected in intestinal contents and plasma; and whether a low dose can alter histomorphological parameters, short-chain fatty acid (SCFA) production, and gut microbiota composition. A total of 60 piglets weaned at 4 weeks were divided into two groups (Control and BBR), each consisting of six pens of five animals. After two weeks of feeding with a normal diet or a berberine-supplemented diet (30 mg berberine/kg feed), berberine and its metabolites were quantified in intestinal contents and plasma by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) on 12 animals per group (2 male piglets per pen). Moreover, villus length and crypt depth were measured in small-intestinal tissue, and 16S rRNA gene sequencing was performed to examine jejunal, cecal, and colonic gut microbiota composition. Our findings show that piglets metabolize berberine into phase I and II metabolites; however, a low dose does not affect their histomorphology, microbiota composition, or SCFA production.

摘要

断奶是仔猪生命中最具挑战性的阶段之一,多种应激源会导致肠道健康不佳。多年来,氧化锌(ZnO)一直是促进肠道健康和预防断奶后腹泻(PWD)的首选方法。然而,自2022年起欧盟禁止在药用水平使用氧化锌,因此需要替代品。黄连素(BBR)是一种异喹啉生物碱,在中药中用于治疗腹泻已有数百年历史,其药理特性可能使该分子成为氧化锌的有吸引力的替代品。本研究的目的是调查黄连素在断奶仔猪的肠道和肝脏中如何代谢;确定在肠道内容物和血浆中检测到哪些代谢物;以及低剂量是否会改变组织形态学参数、短链脂肪酸(SCFA)的产生和肠道微生物群组成。总共60头4周龄断奶的仔猪被分为两组(对照组和黄连素组),每组由六个围栏组成,每个围栏有五只动物。在以正常饮食或添加黄连素的饮食(30毫克黄连素/千克饲料)喂养两周后,通过超高效液相色谱-串联质谱法(UPLC-MS/MS)对每组12只动物(每围栏2只雄性仔猪)的肠道内容物和血浆中的黄连素及其代谢物进行定量。此外,测量小肠组织中的绒毛长度和隐窝深度,并进行16S rRNA基因测序以检查空肠、盲肠和结肠的肠道微生物群组成。我们的研究结果表明,仔猪将黄连素代谢为I期和II期代谢物;然而,低剂量不会影响它们的组织形态、微生物群组成或SCFA的产生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ccb/12383199/ba202d49c981/animals-15-02450-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ccb/12383199/0d23d80802ef/animals-15-02450-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ccb/12383199/ba202d49c981/animals-15-02450-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ccb/12383199/0d23d80802ef/animals-15-02450-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ccb/12383199/ba202d49c981/animals-15-02450-g002.jpg

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本文引用的文献

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From mother to piglet: the lasting influence of the maternal microbiome.从母亲到仔猪:母体微生物群的持久影响。
Anim Microbiome. 2025 May 26;7(1):52. doi: 10.1186/s42523-025-00420-0.
2
Berberine alleviates enterotoxigenic -induced intestinal mucosal barrier function damage in a piglet model by modulation of the intestinal microbiome.黄连素通过调节肠道微生物群减轻仔猪模型中肠毒素诱导的肠黏膜屏障功能损伤。
Front Nutr. 2025 Jan 14;11:1494348. doi: 10.3389/fnut.2024.1494348. eCollection 2024.
3
Berberine alleviates ETEC-induced intestinal inflammation and oxidative stress damage by optimizing intestinal microbial composition in a weaned piglet model.
小檗碱通过优化断奶仔猪模型中的肠道微生物组成来缓解 ETEC 引起的肠道炎症和氧化应激损伤。
Front Immunol. 2024 Sep 16;15:1460127. doi: 10.3389/fimmu.2024.1460127. eCollection 2024.
4
Microbiome and metabolome analyses reveal significant alterations of gut microbiota and bile acid metabolism in ETEC-challenged weaned piglets by dietary berberine supplementation.微生物组和代谢组分析揭示了通过日粮添加小檗碱,受产肠毒素大肠杆菌攻击的断奶仔猪肠道微生物群和胆汁酸代谢发生了显著变化。
Front Microbiol. 2024 Jun 25;15:1428287. doi: 10.3389/fmicb.2024.1428287. eCollection 2024.
5
Berberine-microbiota interplay: orchestrating gut health through modulation of the gut microbiota and metabolic transformation into bioactive metabolites.黄连素与微生物群的相互作用:通过调节肠道微生物群和代谢转化为生物活性代谢物来协调肠道健康。
Front Pharmacol. 2023 Dec 7;14:1281090. doi: 10.3389/fphar.2023.1281090. eCollection 2023.
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Interrelation between gut microbiota, SCFA, and fatty acid composition in pigs.猪肠道微生物群、短链脂肪酸和脂肪酸组成的相互关系。
mSystems. 2024 Jan 23;9(1):e0104923. doi: 10.1128/msystems.01049-23. Epub 2023 Dec 14.
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