Department of Large Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas, United States of America.
The Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, Texas, United States of America.
PLoS One. 2018 Aug 23;13(8):e0202527. doi: 10.1371/journal.pone.0202527. eCollection 2018.
Non-steroidal anti-inflammatory drugs (NSAIDs) are routinely used in both veterinary and human medicine. Gastrointestinal injury is a frequent adverse event associated with NSAID use and evidence suggests that NSAIDs induce gastrointestinal microbial imbalance (i.e., dysbiosis) in both animals and people. It is unknown, however, whether cyclooxygenase (COX)-2-selective NSAIDs induce dysbiosis, or if this phenomenon occurs in horses administered any class of NSAIDs. Therefore, our objectives were to determine whether the composition and diversity of the fecal microbiota of adult horses were altered by NSAID use, and whether these effects differed between non-selective and COX-2-selective NSAIDs. Twenty-five adult horses were randomly assigned to 1 of 3 groups: control (n = 5); phenylbutazone (n = 10); or, firocoxib (n = 10). Treatments were administered for 10 days. Fecal samples were collected every 5 days for 25 days. DNA was extracted from feces and the 16S rRNA gene amplified and sequenced to determine the composition of the microbiota and the inferred metagenome. While the fecal microbiota profile of the control group remained stable over time, the phenylbutazone and firocoxib groups had decreased diversity, and alteration of their microbiota profiles was most pronounced at day 10. Similarly, there were clear alterations of the inferred metagenome at day 10 compared to all other days, indicating that use of both non-selective and selective COX inhibitors resulted in temporary alterations of the fecal microbiota and inferred metagenome. Dysbiosis associated with NSAID administration is clinically relevant because dysbiosis has been associated with several important diseases of horses including abdominal pain (colic), colitis, enteric infections, and laminitis.
非甾体抗炎药（NSAIDs）在兽医和人类医学中都经常使用。胃肠道损伤是与 NSAID 使用相关的常见不良反应事件，有证据表明 NSAIDs 会导致动物和人类的胃肠道微生物失衡（即，肠道菌群失调）。然而，尚不清楚 COX-2 选择性 NSAIDs 是否会引起肠道菌群失调，或者这种现象是否会发生在给予任何 NSAIDs 类别的马中。因此，我们的目的是确定 NSAID 使用是否会改变成年马粪便微生物群的组成和多样性，以及这种影响是否在非选择性和 COX-2 选择性 NSAIDs 之间存在差异。25 匹成年马被随机分配到 3 个组中的 1 个：对照组（n = 5）；苯丁唑酮（n = 10）；或非罗考昔布（n = 10）。治疗持续 10 天。在 25 天内，每 5 天采集一次粪便样本。从粪便中提取 DNA，扩增 16S rRNA 基因并进行测序，以确定微生物群的组成和推断的宏基因组。虽然对照组的粪便微生物群谱随时间保持稳定，但苯丁唑酮和非罗考昔布组的多样性降低，其微生物群谱的改变在第 10 天最为明显。同样，与所有其他天数相比，推断的宏基因组在第 10 天也有明显的改变，这表明使用非选择性和选择性 COX 抑制剂都会导致粪便微生物群和推断的宏基因组的暂时改变。与 NSAID 给药相关的肠道菌群失调与临床相关，因为肠道菌群失调与马的几种重要疾病有关，包括腹痛（绞痛）、结肠炎、肠道感染和蹄叶炎。
