The effect of antibiotics on the gut microbiome: a metagenomics analysis of microbial shift and gut antibiotic resistance in antibiotic treated mice
- 作者列表："Lei Xu","Anil Surathu","Isaac Raplee","Ashok Chockalingam","Sharron Stewart","Lacey Walker","Leonard Sacks","Vikram Patel","Zhihua Li","Rodney Rouse
Abstract Background Emergence of antibiotic resistance is a global public health concern. The relationships between antibiotic use, the gut community composition, normal physiology and metabolism, and individual and public health are still being defined. Shifts in composition of bacteria, antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) after antibiotic treatment are not well-understood. Methods This project used next-generation sequencing, custom-built metagenomics pipeline and differential abundance analysis to study the effect of antibiotic monotherapy on resistome and taxonomic composition in the gut of Balb/c mice infected with E. coli via transurethral catheterization to investigate the evolution and emergence of antibiotic resistance. Results There is a longitudinal decrease of gut microbiota diversity after antibiotic treatment. Various ARGs are enriched within the gut microbiota despite an overall reduction of the diversity and total amount of bacteria after antibiotic treatment. Sometimes treatment with a specific class of antibiotics selected for ARGs that resist antibiotics of a completely different class (e.g. treatment of ciprofloxacin or fosfomycin selected for cepA that resists ampicillin). Relative abundance of some MGEs increased substantially after antibiotic treatment (e.g. transposases in the ciprofloxacin group). Conclusions Antibiotic treatment caused a remarkable reduction in diversity of gut bacterial microbiota but enrichment of certain types of ARGs and MGEs. These results demonstrate an emergence of cross-resistance as well as a profound change in the gut resistome following oral treatment of antibiotics.
文摘背景抗生素耐药性的出现是全球公共卫生关注的问题。抗生素使用、肠道群落组成、正常生理和代谢以及个人和公共卫生之间的关系仍在定义中。抗生素治疗后细菌、抗生素抗性基因 (ARGs) 和移动遗传元件 (MGEs) 组成的变化尚不清楚。方法本项目采用新一代测序,定制的宏基因组学管道和差异丰度分析，研究抗生素单药治疗对感染 E 的 Balb/c 小鼠肠道耐药组和分类组成的影响。大肠杆菌经尿道插管调查抗生素耐药性的演变和出现。结果抗生素治疗后肠道菌群多样性出现纵向下降。尽管抗生素治疗后细菌的多样性和总量总体减少，但各种 ARGs 在肠道菌群内富集。有时用特定类别的抗生素治疗，这些抗生素选择用于对完全不同类别的抗生素有抵抗力的 ARGs (例如，治疗抗氨苄西林的 cepA 选择的环丙沙星或磷霉素)。抗生素治疗后一些 MGEs 的相对丰度大幅增加 (如环丙沙星组的转座酶)。结论抗生素治疗导致肠道细菌菌群多样性显著降低，但某些类型的 ARGs 和 MGEs 富集。这些结果证明了交叉耐药的出现以及口服抗生素治疗后肠道耐药组的深刻变化。
METHODS:OBJECTIVES:To evaluate the effect of esophageal stimulation on nutritional adequacy in critically ill patients at risk for enteral feeding intolerance. DESIGN:A multicenter randomized sham-controlled clinical trial. SETTING:Twelve ICUs in Canada. PATIENTS:We included mechanically ventilated ICU patients who were given moderate-to-high doses of opioids and expected to remain alive and ventilated for an additional 48 hours and who were receiving enteral nutrition or expected to start imminently. INTERVENTIONS:Patients were randomly assigned 1:1 to esophageal stimulation via an esophageal stimulating catheter (E-Motion Tube; E-Motion Medical, Tel Aviv, Israel) or sham treatment. All patients were fed via these catheters using a standardized feeding protocol. MEASUREMENTS AND MAIN RESULTS:The co-primary outcomes were proportion of caloric and protein prescription received enterally over the initial 7 days following randomization. Among 159 patients randomized, the modified intention-to-treat analysis included 155 patients: 73 patients in the active treatment group and 82 in the sham treatment group. Over the 7-day study period, the percent of prescribed caloric intake (± SE) received by the enteral route was 64% ± 2 in the active group and 65% ± 2 in sham patients for calories (difference, -1; 95% CI, -8 to 6; p = 0.74). For protein, it was 57% ± 3 in the active group and 60% ± 3 in the sham group (difference, -3; 95% CI, -10 to 3; p = 0.30). Compared to the sham group, there were more serious adverse events reported in the active treatment group (13 vs 6; p = 0.053). Clinically important arrhythmias were detected by Holter monitoring in 36 out of 70 (51%) in the active group versus 22 out of 76 (29%) in the sham group (p = 0.006). CONCLUSIONS:Esophageal stimulation via a special feeding catheter did not improve nutritional adequacy and was associated with increase risk of harm in critically ill patients.
METHODS:RATIONALE:The long-term effects of delivering approximately 100% of recommended calorie intake via the enteral route during critical illness compared to a lesser amount of calories are unknown. OBJECTIVES:Our hypotheses were that achieving approximately 100% of recommended calorie intake during critical illness would increase quality of life scores, return to work and key life activities and reduce death and disability six months later. METHODS:We conducted a multicenter, blinded, parallel group, randomized clinical trial, with 3957 mechanically ventilated critically ill adults allocated to energy-dense (1.5 kcal/ml) or routine (1.0 kcal/ml) enteral nutrition. MEASUREMENTS AND MAIN RESULTS:Participants assigned energy-dense nutrition received more calories (% recommended energy intake, mean (SD) (energy-dense: 103% (28) vs. usual: 69% (18)). Mortality at day-180 was similar (560/1895 (29.6%) vs. 539/1920 (28.1%); relative risk 1.05 (95%CI, 0.95 to 1.16)). At a median [IQR] of 185 [182, 193] days after randomization, 2492 survivors were surveyed and reported similar quality of life (EuroQol five dimensions five-level quality of life questionnaire visual analogue scale, median [IQR]: 75 [60-85]; group difference: 0 (95%CI, 0 to 0)). Similar numbers of participants returned to work with no difference in hours worked or effectiveness at work (n=818). There was no observed difference in disability (n=1208) or participation in key life activities (n=705). CONCLUSIONS:The delivery of approximately 100% compared to 70% of recommended calorie intake during critical illness does not improve quality of life, or functional outcomes, or increase the number of survivors six months later. Clinical trial registration available at www.clinicaltrials.gov, ID: NCT02306746.
METHODS:BACKGROUND:Provision of enteral nutrition with jejunal feeding in upper gastrointestinal obstruction is highly recommended. Access to jejunum can be obtained surgically, percutaneously, or endoscopically. Our institution routinely and preferentially utilizes a silicone nasojejunal tube that is inserted past the obstruction endoscopically. We use a custom dual channel tube that allows feeding at the distal tip and another channel 40 cm from the tip that enables decompression proximally. This is a report of our experience with this custom nasojejunal tube. METHODS:This is a prospective observational study of 201 patients who underwent endoscopic nasojejunal wire-guided feeding tube insertions for obstruction of either the esophagus or the stomach including both benign and malignant pathologies between January 2015 to June 2018 in Hospital Sungai Buloh and Hospital Sultanah Aminah, Malaysia. The indications for tube insertion, insertion technique, and tube-related problems were described. RESULTS:The nasojejunal tube was used to establish enteral feeding in patients with obstructing tumors of the distal esophagus in 65 patients (32.3%) and gastric outlet obstruction in 72 patients (35.8%). There were 54 patients (26.9%) who required reinsertion. The most common reason for reinsertion was unintentional dislodgement, where 32 patients (15.9%) followed by tube blockage 20 patients (10.0%). Using our method of advancement under direct vision, we had only 2 cases of malposition due to severely deformed anatomy. We had no incidence of aspiration in this group of patients and overall, the patients tolerated the tube well. CONCLUSIONS:The novel nasojejunal feeding tube with gastric decompression function is a safe and effective method of delivery of enteral nutrition in patients with upper gastrointestinal obstruction. These tubes if inserted properly are well tolerated with almost no risk of malposition and are tolerated well even for prolonged periods of time until definitive surgery could be performed.