Abstract：
Probiotics have the potential to prevent disruptions to normal gastrointestinal function caused by oral antibiotic use. In this study, we examined the capacity of Bifidobacterium animalis subspecies lactis BB-12 (BB-12) and yogurt, separately and combined, to mitigate the effects of the antibiotic amoxicillin-clavulanate (AMC) on the gut microbiota and metabolomes of C57BL/6 J mice. Male and female mice were administered either BB-12, yogurt, BB-12 in yogurt, or saline for 10 days concurrent with the inclusion of AMC in the drinking water. Male mice exposed to AMC exhibited significant reductions (p<0.05) in body weight over the course of the study compared to sham (no AMC) controls whereas no such effects were observed for female mice. AMC administration resulted in rapid alterations to the intestinal microbiota in both sexes irrespective of BB-12 or yogurt treatment, including significant (p<0.05) losses in bacterial cell numbers and changes in microbial alpha-diversity and beta-diversity in the feces and cecal contents. The effects of AMC on the gut microbiota were observed within one day of administration and the bacterial contents continued to change over time, showing a succession marked by rapid reductions in Muribaculaceae and Lachnospiraceae and temporal increases in proportions of Acholeplasmataceae (day 1) and Streptococcaceae and Leuconostocaceae (day 5). By day 10 of AMC intake, high proportions of Gammaproteobacteria assigned as Erwiniaceae or Enterobacteriaceae (average of 63 %), were contained in the stools and were similarly enriched in the cecum. The cecal contents of mice given AMC harbored significantly reduced concentrations of (branched) short-chain fatty acids (SCFA), aspartate, and other compounds, whereas numerous metabolites, including formate, lactate, and several amino acids and amino acid derivatives were significantly enriched. Despite the extensive impact of AMC, starting at day 7 of the study, the body weights of male mice given yogurt or BB-12 (in saline) with AMC were similar to the healthy controls. BB-12 (in saline) and yogurt intake was associated with increased Streptococcaceae and both yogurt and BB-12 resulted in lower proportions of Erwiniaceae in the fecal and cecal contents. The cecal contents of mice fed BB-12 in yogurt contained levels of formate, glycine, and glutamine that were equivalent to the sham controls. These findings highlight the potential of BB-12 and yogurt to mitigate antibiotic-induced gut dysbiosis.
摘要：
益生菌有可能防止口服抗生素对正常胃肠功能的破坏。在这项研究中,我们检查了动物双歧杆菌亚种乳酸BB-12（BB-12）和酸奶的能力，分开和组合，减轻抗生素阿莫西林-克拉维酸（AMC）对C57BL/6J小鼠肠道菌群和代谢组的影响。给雄性和雌性小鼠服用BB-12，酸奶，酸奶中的BB-12,或盐水10天，同时在饮用水中包含AMC。与假(无AMC)对照相比,暴露于AMC的雄性小鼠在研究过程中表现出体重的显著降低(p<0.05),而对于雌性小鼠没有观察到这种作用。无论BB-12或酸奶治疗如何，AMC管理都会导致两性肠道微生物群的快速改变。包括细菌细胞数量的显着（p<0.05）损失以及粪便和盲肠内容物中微生物α-多样性和β-多样性的变化。在给药一天内观察到AMC对肠道微生物群的影响，并且细菌含量随时间持续变化，表现出演替，其特征是Muribaculaceae和Lachnospienceae的快速减少，而Acholeplasaceae（第1天），链球菌科和明串管科（第5天）的比例随时间增加。到AMC摄入量的第10天，高比例的γ变形杆菌被指定为Erwiniaceae或肠杆菌科（平均为63％），包含在粪便中，并在盲肠中同样富集。给予AMC的小鼠的盲肠内容物包含显着降低的（分支）短链脂肪酸（SCFA）浓度，天冬氨酸,和其他化合物，而大量的代谢物，包括甲酸盐，乳酸，并显著富集了几种氨基酸和氨基酸衍生物。尽管AMC产生了广泛的影响，从研究的第7天开始，给予AMC酸奶或BB-12（在盐水中）的雄性小鼠的体重与健康对照相似。BB-12（在盐水中）和酸奶的摄入量与链球菌科的增加有关，而酸奶和BB-12均导致粪便和盲肠内容物中的芥菜科所占比例较低。在酸奶中饲喂BB-12的小鼠的盲肠内容物含有甲酸盐水平，甘氨酸,和相当于假对照的谷氨酰胺。这些发现强调了BB-12和酸奶减轻抗生素诱导的肠道生态失调的潜力。
