Antibiotics are commonly given to horses to treat known bacterial infections or as prophylaxis against the development of infection. Diarrhea is a recognized adverse effect of antimicrobial administration in horses (antimicrobial associated diarrhea, AAD). In veterinary referral centers, AAD has a reported incidence of 22 to 94% (McGorum, 2010), while horses with AAD are 4.5 times more likely to die compared with horses with other types of colitis (Woods and Cohen, 1999). Although all antibiotics have potential to induce diarrhea, some have increased risk due to low oral absorption, biliary excretion, or enterohepatic recycling. The role of dysbiosis in the gut microbiota is a key feature in the pathogenesis of AAD. Disruption of commensal bacteria of the hindgut allows for pathogen overgrowth and alteration in microbial metabolic function. To date, 16S rRNA sequencing has been used to characterize the effects of penicillin, trimethoprim sulfa, doxycycline, erythromycin, ceftiofur, enrofloxacin, oxytetracycline and metronidazole on the fecal microbiome in healthy horses (Costa et al., 2015; Arnold et al., 2020; Liepman, 2022). Regardless of mechanism of action, antibiotics typically reduce diversity (species richness and evenness) and alter the bacterial community structure of the fecal microbiome, even when animals maintain normal health status and fecal character (Arnold et al., 2021). These effects typically require at least 30 days before the microbiome returns to baseline (Gomez et al, 2023). In horses with colitis, changes in the microbiome are often significant. Horses with AAD demonstrate the most severe disruption of the fecal microbiome compared with horses with Salmonella or undifferentiated colitis. These changes are evident from the phylum to species level, and include important phyla such as Bacteroidetes, Firmicutes, Fibrobacter and Verrucomicrobia (Arnold et al., 2020; Liepman, 2022; Costa et al., 2015). Alterations in the microbiota result in functional metabolic changes that are clinically manifested by diarrhea. Potential changes include alterations in the metabolism of bile acids, carbohydrates including short chain fatty acids, amino acids, lipids and proteins. There is also evidence that antimicrobials increase intestinal permeability via effects on tight junction proteins and by compromising the barrier function provided by the mucus layer between the enterocytes and gut lumen. Recent work comparing horses on antimicrobials that did and did not develop diarrhea confirm that horses with diarrhea have depletion of Verrocomicrobia and metabolites related to gastrointestinal barrier function (Arnold et al., 2021).

中文翻译：

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146 抗菌剂和抗菌剂相关腹泻对马粪便微生物组的影响


抗生素通常用于马匹治疗已知的细菌感染或预防感染的发展。腹泻是公认的马匹抗菌药物给药的不良反应（抗菌相关腹泻，AAD）。在兽医转诊中心，据报道 AAD 的发病率为 22% 至 94%（McGorum，2010 年），而患有 AAD 的马死亡的可能性是患有其他类型结肠炎的马的 4.5 倍（Woods 和 Cohen，1999 年）。尽管所有抗生素都有可能诱发腹泻，但有些抗生素由于口服吸收率低、胆汁排泄或肠肝循环作用低而风险增加。菌群失调在肠道菌群中的作用是 AAD 发病机制的一个关键特征。后肠共生细菌的破坏导致病原体过度生长和微生物代谢功能的改变。迄今为止，16S rRNA 测序已被用于表征青霉素、甲氧苄啶磺胺、多西环素、红霉素、头孢噻呋、恩诺沙星、土霉素和甲硝唑对健康马粪便微生物组的影响（Costa等人，2015 年;Arnold等人，2020 年;Liepman，2022 年）。无论作用机制如何，即使动物保持正常的健康状况和粪便特性，抗生素通常会降低多样性（物种丰富度和均匀度）并改变粪便微生物组的细菌群落结构（Arnold等人，2021 年）。这些影响通常需要至少 30 天才能使微生物组恢复到基线（Gomez等人，2023 年）。在患有结肠炎的马中，微生物组的变化通常很大。与患有沙门氏菌或未分化结肠炎的马相比，患有 AAD 的马表现出最严重的粪便微生物组破坏。 这些变化从门到物种水平都很明显，包括重要的门，如拟杆菌门、厚壁菌门、纤维杆菌门和疣微菌门（Arnold等人，2020 年;利普曼，2022 年;Costa等人，2015 年）。微生物群的改变导致功能性代谢变化，临床表现为腹泻。潜在的变化包括胆汁酸、碳水化合物（包括短链脂肪酸）、氨基酸、脂质和蛋白质代谢的改变。还有证据表明，抗菌剂通过影响紧密连接蛋白和破坏肠上皮细胞和肠腔之间的粘液层提供的屏障功能来提高肠道通透性。最近的工作比较了服用和未发生腹泻的马服用抗菌剂，证实腹泻的马消耗了与胃肠道屏障功能相关的 Verrocomicrobia 和代谢物（Arnold 等人，2021 年）。