Editorial: Allostatic Load and Inflammatory Bowel Disease

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. Jeli Mendoza: writing – review and editing. James Irwin: writing – review and editing. This article is linked to Zhao et al papers. To view these articles, visit https://doi.org/10.1111/apt.18217 and https://doi.org/10.1111/apt.18414. Data sharing is not applicable to this article as no new data were created or analyzed in this study.