The construct that chronic stress causes illness, and that reducing stress improves health, is widely accepted and heavily researched. Zhao et al. demonstrate an association between an allostatic load biomarker panel (ALBP; blood pressure, heart rate, HbA1c, cholesterol, waist-to-hip ratio [WHR], CRP, IGF-1, creatinine) and the incidence and severity of inflammatory bowel disease (IBD), in a cohort from the UK Biobank [1].

Allostasis refers to one's ability to maintain physiological stability in response to environmental stress through the neuroendocrine system. Allostatic load (AL) refers to the cumulative physiological burden placed on the body due to chronic stress and dysregulation of stress-response systems. The widely accepted measurable primary mediators of AL are cortisol, serum dehydroepiandrosterone sulfate (DHEAS), adrenaline and noradrenaline. The original secondary outcome measures of AL (physiological parameters that may be altered by chronic stress) are systolic blood pressure, diastolic blood pressure, high-density lipoproteins, total cholesterol, glycosylated haemoglobin and abdominal obesity (measured by waist-to-hip ratio) [2]. Many studies have endeavoured to link AL with cardiovascular disease, general functional decline, cognitive decline and development of metabolic syndrome. Two major issues commonly occur: firstly, a difficulty in demonstrating a causal relationship between AL and measured biomarkers and secondly, a difficulty in quantifying longitudinal AL. Both of these issues are present in this study.

Zhao et al. utilised the UK Biobank, which has recorded environmental, lifestyle and genetic data on 500,000 participants collected since 2006. Participants have more than thirty key biochemistry markers recorded at baseline. An ALBP was defined for this study using this data from a single point in time. Participants with high ALBP scores were shown to have a greater risk of developing IBD.

The correlation between the ALBP and outcomes in this study is robust. However, the correlation between AL and the ALBP is assumed. Primary mediators of AL are not included in the ALBP. There is no convincing data in the literature demonstrating a causal relationship between exposure to chronic stress (AL) and secondary outcome measures [3]. Notably, there is a significant overlap between secondary mediators of AL and the criteria for metabolic syndrome. Out of context, this study could be interpreted as demonstrating an association between metabolic syndrome and the incidence of IBD. Additionally, it is difficult to capture true AL, which is an accumulation of stress, from baseline data.

This study provides clear evidence that this specific ALBP is associated with development of IBD. However, as in other studies, the relationship between AL and the ALBP is unclear. This line of research ultimately asks whether a reduction in AL through lifestyle and environmental change may lower IBD incidence. In order to answer this question, a standardised and validated research definition of longitudinal AL is required, which then needs to be correlated to a standardised and validated ALBP. Given the temporal variability of AL, the timeframe required to make observations of outcome, and the inherent observational nature of study design in human AL research, this is challenging to achieve. A causal relationship between AL and IBD incidence is yet to be determined.

慢性压力会导致疾病，而减轻压力可以改善健康，这一结构被广泛接受并进行了大量研究。Zhao 等人在英国生物样本库的一个队列中证明了异体负荷生物标志物组（ALBP;血压、心率、HbA1c、胆固醇、腰臀比 [WHR]、CRP、IGF-1、肌酐）与炎症性肠病 （IBD） 的发病率和严重程度之间存在关联 [1]。

失变是指一个人通过神经内分泌系统对环境压力做出反应而保持生理稳定性的能力。异体负荷 （AL） 是指由于慢性压力和压力反应系统失调而施加在身体上的累积生理负担。广泛接受的 AL 可测量的主要介质是皮质醇、血清硫酸脱氢表雄酮 （DHEAS）、肾上腺素和去甲肾上腺素。AL 的原始次要结局指标（可能因慢性应激而改变的生理参数）是收缩压、舒张压、高密度脂蛋白、总胆固醇、糖化血红蛋白和腹部肥胖（通过腰臀比测量）[2]。许多研究试图将 AL 与心血管疾病、一般功能下降、认知能力下降和代谢综合征的发展联系起来。通常会出现两个主要问题：首先，难以证明 AL 与测量的生物标志物之间的因果关系，其次，难以量化纵向 AL。本研究中存在这两个问题。

Zhao 等人利用了英国生物样本库，该样本库记录了自 2006 年以来收集的 500,000 名参与者的环境、生活方式和遗传数据。参与者在基线时记录了 30 多个关键生化标志物。本研究使用来自单个时间点的这些数据定义了 ALBP。ALBP 评分高的参与者患 IBD 的风险更大。

ALBP 与本研究结果之间的相关性很强。然而，假设 AL 和 ALBP 之间存在相关性。ALP 中不包括 AL 的主要介质。文献中没有令人信服的数据证明暴露于慢性应激 （AL） 与次要结果测量之间存在因果关系 [3]。值得注意的是，AL 的次级介质与代谢综合征的标准之间存在显著重叠。在上下文之外，这项研究可以解释为证明了代谢综合征与 IBD 发病率之间的关联。此外，很难从基线数据中捕获真正的 AL，即应力的积累。

这项研究提供了明确的证据，证明这种特异性 ALBP 与 IBD 的发展有关。然而，与其他研究一样，AL 和 ALBP 之间的关系尚不清楚。这一系列研究最终询问了通过生活方式和环境改变减少 AL 是否可以降低 IBD 的发病率。为了回答这个问题，需要一个标准化和经过验证的纵向 AL 研究定义，然后需要将其与标准化和经过验证的 ALBP 相关联。鉴于 AL 的时间可变性、观察结果所需的时间框架以及人类 AL 研究中研究设计的固有观察性质，这很难实现。AL 和 IBD 发病率之间的因果关系尚未确定。