Centre for Research in Epidemiology and Population Health (CESP), INSERM U1018, Université Paris-Saclay, Université Paris-Sud, VillejuifFrance.
Internal Medicine Department, AP-HP, Nord, Université de Paris, Hôpital Beaujon, ClichyFrance.
Rheumatology (Oxford). 2020 Dec 1;59(12):3767-3775. doi: 10.1093/rheumatology/keaa133.
To assess the relationship between gastrointestinal disorders and the risk of further development of RA.
The Etude Epidémiologique auprès des femmes de la Mutuelle générale de l'Education Nationale-European Prospective Investigation into Cancer and Nutrition Study is a French prospective cohort including 98 995 healthy women since 1990. Participants completed mailed questionnaires on their lifestyles and health-related information. Gastrointestinal disorders were assessed in the third questionnaire (sent in 1993). Hazard ratios and 95% CIs for incident RA were estimated using Cox proportional hazards regression models with age as the time scale. Models were age adjusted, and then additionally adjusted for known risk factors of RA such as smoking, and for potential cofounders.
Among 65 424 women, 530 validated incident RA cases were diagnosed after a mean (s.d.) of 11.7 (5.9) years after study baseline. In comparison with no gastrointestinal disorder, chronic diarrhoea was associated with an increased risk of developing RA during follow-up (hazard ratio = 1.70, 95% CI 1.13, 2.58), independently of dysthyroidism or dietary habits. The association was stronger among ever-smokers (hazard ratio = 2.21, 95% CI 1.32, 3.70). There was no association between RA risk and constipation or alternating diarrhoea/constipation.
Chronic diarrhoea was associated with an increased risk of subsequent RA development, particularly among ever-smokers. These data fit with the mucosal origin hypothesis of RA, where interaction between intestinal dysbiosis and smoking could occur at an early stage to promote emergence of autoimmunity, followed years later by clinical disease.
评估胃肠道疾病与类风湿关节炎（RA）进一步发展风险之间的关系。
女性教育互助会（Mutuelle générale de l'Education Nationale）欧洲前瞻性癌症与营养研究（Etude Epidémiologique auprès des femmes de la Mutuelle générale de l'Education Nationale-European Prospective Investigation into Cancer and Nutrition Study）是一项法国前瞻性队列研究，自 1990 年起纳入 98995 名健康女性。参与者通过邮寄问卷完成了关于生活方式和健康相关信息的调查。胃肠道疾病在第三次问卷（1993 年寄出）中进行评估。使用 Cox 比例风险回归模型，以年龄作为时间尺度，估计新发 RA 的风险比（HR）和 95%置信区间（CI）。模型在年龄调整的基础上，进一步调整了 RA 的已知危险因素（如吸烟）和潜在混杂因素。
在 65424 名女性中，在研究基线后平均（标准差）11.7（5.9）年诊断出 530 例确诊的新发 RA 病例。与无胃肠道疾病相比，慢性腹泻与随访期间发生 RA 的风险增加相关（HR=1.70，95%CI 1.13，2.58），与甲状腺功能异常或饮食习惯无关。在曾经吸烟者中，这种关联更强（HR=2.21，95%CI 1.32，3.70）。便秘或腹泻与便秘交替与 RA 风险之间无关联。
慢性腹泻与随后 RA 发展的风险增加相关，尤其是在曾经吸烟者中。这些数据符合 RA 的黏膜起源假说，即肠道菌群失调与吸烟之间的相互作用可能在早期发生，从而促进自身免疫的出现，数年后出现临床疾病。
