摘要
出身背景
婴儿感染致命疾病的风险很高，他们的治疗依赖于有效的抗生素。抗生素耐药性基因（ARGs）在未使用抗生素的婴儿肠道微生物群中大量存在，耐药性感染导致的婴儿死亡率很高。抗生素在形成婴儿耐药性中的作用已经被研究过，但对影响婴儿肠道抗生素耐药性负担的其他因素的了解有限。
目标
我们的目的是确定早期接触配方奶粉对早产或足月新生儿和婴儿ARG负荷的影响。我们的假设是，饮食会导致选择性压力，从而影响婴儿肠道的微生物群落，而配方奶粉暴露会增加携带ARGs的类群的丰度。
方法
对46名新生儿的肠道宏基因组进行横断面取样，建立一个广义线性模型，以确定饮食对新生儿ARG负荷的影响。该模型使用从公共数据库收集的新生儿宏基因组进行交叉验证，使用我们的自定义统计管道进行交叉验证。
后果
配方奶粉喂养的新生儿机会性病原体的相对丰度较高，如金黄色葡萄球菌、表皮葡萄球菌、肺炎克雷伯菌、氧化克雷伯杆菌和艰难梭菌。与纯母乳喂养的婴儿相比，配方奶粉喂养组肠道细菌携带的ARGs的相对丰度高69%（倍数变化，1.69；95%置信区间：1.12–2.55；P=0.013；n=180）。配方奶粉喂养的婴儿也有明显较少的典型婴儿细菌，如双歧杆菌，这些细菌对健康有潜在益处。
结论
这一新发现表明，配方奶粉暴露与新生儿ARG负担较高有关，这为临床医生除了在生命的最初几个月使用抗生素外，还应考虑喂养模式，以最大限度地减少婴儿体内抗生素耐药性肠道细菌的增殖奠定了基础。
ABSTRACT
Background
Infants are at a high risk of acquiring fatal infections, and their treatment relies on functioning antibiotics. Antibiotic resistance genes (ARGs) are present in high numbers in antibiotic-naive infants’ gut microbiomes, and infant mortality caused by resistant infections is high. The role of antibiotics in shaping the infant resistome has been studied, but there is limited knowledge on other factors that affect the antibiotic resistance burden of the infant gut.

Objectives
Our objectives were to determine the impact of early exposure to formula on the ARG load in neonates and infants born either preterm or full term. Our hypotheses were that diet causes a selective pressure that influences the microbial community of the infant gut, and formula exposure would increase the abundance of taxa that carry ARGs.

Methods
Cross-sectionally sampled gut metagenomes of 46 neonates were used to build a generalized linear model to determine the impact of diet on ARG loads in neonates. The model was cross-validated using neonate metagenomes gathered from public databases using our custom statistical pipeline for cross-validation.

Results
Formula-fed neonates had higher relative abundances of opportunistic pathogens such as Staphylococcus aureus, Staphylococcus epidermidis, Klebsiella pneumoniae, Klebsiella oxytoca, and Clostridioides difficile. The relative abundance of ARGs carried by gut bacteria was 69% higher in the formula-receiving group (fold change, 1.69; 95% CI: 1.12–2.55; P = 0.013; n = 180) compared to exclusively human milk–fed infants. The formula-fed infants also had significantly less typical infant bacteria, such as Bifidobacteria, that have potential health benefits.

Conclusions
The novel finding that formula exposure is correlated with a higher neonatal ARG burden lays the foundation that clinicians should consider feeding mode in addition to antibiotic use during the first months of life to minimize the proliferation of antibiotic-resistant gut bacteria in infants.

https://academic.oup.com/ajcn/article/115/2/407/6408461?login=false