Cleveland Clinic, Cleveland, Ohio.
JPEN J Parenter Enteral Nutr. 2013 Nov;37(6):763-74. doi: 10.1177/0148607113486809. Epub 2013 Apr 29.
Antibiotic therapy negatively alters the gut microbiota. Lactobacillus GG (LGG) decreases antibiotic-associated diarrhea (AAD) symptoms, but the mechanisms are unknown. Butyrate has beneficial effects on gut health. Altered intestinal gene expression occurs in the absence of gut microbiota. We hypothesized that antibiotic-induced changes in gut microbiota reduce butyrate production, varying genes involved with gut barrier integrity and water and electrolyte absorption, lending to AAD, and that simultaneous supplementation with LGG and/or tributyrin would prevent these changes.
C57BL/6 mice aged 6-8 weeks received a chow diet while divided into 8 treatment groups (± saline, ± LGG, ± tributyrin, or both). Mice received treatments orally for 7 days with ± broad-spectrum antibiotics. Water intake was recorded daily and body weight was measured. Intestine tissue samples were obtained and analyzed for expression of genes and proteins involved with water and electrolyte absorption, butyrate transport, and gut integrity via polymerase chain reaction and immunohistochemistry.
Antibiotics decreased messenger RNA (mRNA) expression (butyrate transporter and receptor, Na(+)/H(+) exchanger, Cl(-)/HCO3 (-), and a water channel) and protein expression (butyrate transporter, Na(+)/H(+) exchanger, and tight junction proteins) in the intestinal tract. LGG and/or tributyrin supplementation maintained intestinal mRNA expression to that of the control animals, and tributyrin maintained intestinal protein intensity expression to that of control animals.
Broad-spectrum antibiotics decrease expression of anion exchangers, butyrate transporter and receptor, and tight junction proteins in mouse intestine. Simultaneous oral supplementation with LGG and/or tributyrin minimizes these losses. Optimizing intestinal health with LGG and/or tributyrin may offer a preventative therapy for AAD.
抗生素治疗会对肠道微生物群产生负面影响。嗜酸乳杆菌 GG(LGG)可减少抗生素相关性腹泻(AAD)的症状,但具体机制尚不清楚。丁酸盐对肠道健康有益。肠道微生物群缺失时会改变肠道基因表达。我们假设,抗生素引起的肠道微生物群变化会减少丁酸盐的产生,从而改变与肠道屏障完整性以及水和电解质吸收相关的基因,导致 AAD,同时补充 LGG 和/或三丁酸甘油酯可预防这些变化。
6-8 周龄 C57BL/6 小鼠接受标准饮食,同时分为 8 个治疗组(±生理盐水、±LGG、±三丁酸甘油酯、或两者皆有)。小鼠经口接受治疗 7 天,同时接受广谱抗生素治疗。每天记录饮水量,每周测量体重。获取肠道组织样本,通过聚合酶链反应和免疫组织化学分析,研究与水和电解质吸收、丁酸盐转运以及肠道完整性相关的基因和蛋白的表达。
抗生素降低了肠道中信使 RNA(mRNA)的表达(丁酸盐转运体和受体、Na(+)/H(+)交换体、Cl(-)/HCO3 (-)和水通道)和蛋白表达(丁酸盐转运体、Na(+)/H(+)交换体和紧密连接蛋白)。LGG 和/或三丁酸甘油酯补充剂维持了肠道 mRNA 表达,使其与对照动物相似,三丁酸甘油酯还维持了肠道蛋白强度表达,使其与对照动物相似。
广谱抗生素降低了小鼠肠道中阴离子交换体、丁酸盐转运体和受体以及紧密连接蛋白的表达。同时口服补充 LGG 和/或三丁酸甘油酯可最大限度减少这些损失。通过 LGG 和/或三丁酸甘油酯优化肠道健康可能为 AAD 提供预防治疗。