As the global prevalence of inflammatory bowel disease (IBD) is increasing, emphasis has been placed on identifying modifiable risk factors that can aid in prevention [1]. Early-life factors, including antibiotic use and the occurrence of infections, increase the risk of developing IBD [2, 3]. This has been demonstrated in several studies, including a large-scale population-based study in Denmark, which found that antibiotic use was associated with an 84% increase in the risk of developing IBD in childhood [4]. However, most of these studies were unable to disentangle whether this increased risk was attributable to underlying infection, the use of antibiotics or, potentially, both.

Marild et al. capitalised on using parent questionnaire data from two Scandinavian birth cohorts, assessing whether antibiotic exposure and/or infections in the first 3 years of life increased the risk of IBD [5]. They concluded that early-life antibiotic use, independent of infection frequency, was associated with an increased risk of developing IBD. Furthermore, there was no clear association between the number of childhood infections and the later development of IBD, although up to 20% of data were missing. This was similar to the findings by Oh et al., in which a dose-dependent association was seen between childhood antibiotic use and the development of IBD, independent of type of underlying infection [6].

Interestingly, however, Marild et al. noted differential findings when stratifying by antibiotic subtype. Penicillins (narrow and broad-spectrum) increased the risk of IBD when utilised within the first year of life; non-penicillin antibiotics increased the risk of IBD when used during the first 1–3 years of life. Although the significance of this remains uncertain, it does imply that antibiotic use may contribute to the development of IBD differently through the ages. We see evidence of this in prior studies, as individual classes of antibiotics posed differential risks for the development of IBD based on both an individual's chronological age as well as the antibiotic's potential impact on the intestinal microbiome [7, 8].

Additionally, although the link between antibiotic use and incident IBD has been uniformly demonstrated, the link between an underlying infection and the later development of IBD has not. This study, in contrast to prior data by Axelrad et al., demonstrated that frequency of infections in childhood may not be a significant risk factor for childhood IBD [9]. This may be due to the inclusion of milder infections, as these survey-based data do not rely on clinical codes which inherently exclude mild infections managed at home. To this end, when stratifying by severity of infection, Marild et al. did find that infections requiring hospitalisation were associated with a 35% increase in risk of IBD [5].

While this study centres on the first 3 years of life—a critical period for immune and microbiome development—future work must also account for exposures that continue to occur throughout life. This will deepen our understanding of long-term risk factors for developing IBD and pave the way for future preventive strategies.

随着炎症性肠病 （IBD） 的全球患病率不断增加，人们将重点放在识别有助于预防的可改变危险因素上 [1]。早期生活因素，包括抗生素的使用和感染的发生，会增加患 IBD 的风险 [2， 3]。多项研究证实了这一点，包括丹麦的一项大规模人群研究，该研究发现抗生素使用与儿童期 IBD 风险增加 84% 相关 [4]。然而，这些研究中的大多数无法理清这种风险增加是否归因于潜在的感染、抗生素的使用，或者可能两者兼而有之。

Marild 等人利用来自两个斯堪的纳维亚出生队列的父母问卷数据，评估了出生后前 3 年的抗生素暴露和/或感染是否会增加 IBD 的风险 [5]。他们得出结论，与感染频率无关的早期抗生素使用与患 IBD 的风险增加有关。此外，儿童感染的数量与 IBD 的后期发展之间没有明确的关联，尽管高达 20% 的数据缺失。这与 Oh 等人的发现相似，其中儿童抗生素使用与 IBD 的发展之间存在剂量依赖性关联，与潜在感染的类型无关 [6]。

然而，有趣的是，Marild 等人在按抗生素亚型分层时注意到了不同的发现。青霉素类（窄谱和广谱）在出生后第一年内使用会增加患 IBD 的风险;在出生后的前 1-3 年使用非青霉素抗生素会增加患 IBD 的风险。尽管其意义仍不确定，但它确实意味着抗生素的使用可能会随着时间的推移而以不同的方式导致 IBD 的发展。我们在以前的研究中看到了这一点的证据，因为根据个体的实际年龄以及抗生素对肠道微生物组的潜在影响，个别类别的抗生素对 IBD 的发展构成不同的风险 [7， 8]。

此外，尽管抗生素使用与新发 IBD 之间的联系已得到一致证明，但潜在感染与 IBD 后期发展之间的联系尚未得到证实。与 Axelrad 等人之前的数据相比，这项研究表明，儿童期感染频率可能不是儿童 IBD 的重要危险因素 [9]。这可能是由于纳入了较轻的感染，因为这些基于调查的数据不依赖于临床代码，而临床代码本身就排除了在家管理的轻度感染。为此，在按感染严重程度进行分层时，Marild 等人确实发现，需要住院治疗的感染与 IBD 风险增加 35% 相关 [5]。

虽然这项研究侧重于生命的前 3 年——免疫和微生物组发育的关键时期——但未来的工作还必须考虑一生中持续发生的暴露。这将加深我们对患 IBD 的长期风险因素的理解，并为未来的预防策略铺平道路。