Department of Nutrition, Rouen University Hospital, CHU Rouen, France; Université de Rouen Normandie, Inserm UMR1073 « Nutrition, Inflammation and Microbiota-gut-brain Axis », Institute for Research and Innovation in Biomedicine, Rouen, France; Clinical Investigation Center CIC 1404 - Biological Resources Centre, Inserm, Rouen University Hospital, CHU Rouen, France.
PISSARO Proteomics Platform, HeRacLeS High-tech Research Infrastructures for Life, UMS 51 - UAR 2026, Inserm, CNRS, Université de Rouen Normandie, Rouen, France.
Clin Nutr. 2022 Aug;41(8):1752-1758. doi: 10.1016/j.clnu.2022.06.036. Epub 2022 Jun 30.
BACKGROUND & AIMS: In the last decades, the role of microbiota-gut-brain axis has emerged in the regulation of eating behavior and in the pathophysiology of anorexia nervosa (AN) that remains poorly understood. Particularly, a gut-derived dysregulation of immune response has been proposed leading to immunoglobulins directed against appetite-regulating peptides. However, intestinal permeability in patients with anorexia nervosa has been poorly documented.
In the present prospective case-control study, we thus compared intestinal permeability, appetite-regulating peptides and their reactive immunoglobulins measured in severely malnourished women with AN (n = 17; 28 [21-35] y; 14.9 [14.1-15.2] kg/m) to healthy volunteers (HV, n = 34; 26 [23-35] y; 22.3 [20.6-23.6] kg/m).
Patients with AN exhibited an increased urinary lactulose/mannitol ratio, both in 0-5 h (0.033 [0.013-0.116]) and 5-24 h samples (0.115 [0.029-0.582]), when compared to HV (0.02 [0.008-0.045], p = 0.0074 and 0.083 [0.019-0.290], p = 0.0174, respectively), suggesting an increased intestinal permeability. Urinary excretion of sucralose and plasma zonulin were not different. The levels of plasma total ghrelin and desacyl-ghrelin were increased in patients with AN compared to HV, whereas plasma leptin concentration was decreased. In addition, αMSH remained unchanged compared to HV. Finally, we did not observe any modification of the levels of total or free αMSH, leptin or ghrelin-reactive immunoglobulin G and M, as well as for their affinity properties. Only, a weak decrease of the dissociation constant (kd) for acyl-ghrelin-reactive IgG was observed in patients with AN (p = 0.0411).
In conclusion, severely malnourished patients with AN show a higher intestinal permeability than HV without evidence of an effect on appetite regulating peptides-reactive immunoglobulins.
在过去的几十年中，肠道微生物群-肠道-大脑轴在调节进食行为和厌食症（AN）的病理生理学中的作用已经显现出来，但仍知之甚少。特别是，有人提出肠道来源的免疫反应失调会导致针对调节食欲的肽的免疫球蛋白。然而，厌食症患者的肠道通透性尚未得到充分记录。
在本前瞻性病例对照研究中，我们比较了严重营养不良的 AN 患者（n=17；28[21-35]岁；14.9[14.1-15.2]kg/m2）与健康志愿者（HV，n=34；26[23-35]岁；22.3[20.6-23.6]kg/m2）的肠道通透性、食欲调节肽及其反应性免疫球蛋白。
与 HV 相比，AN 患者在 0-5 h（0.033[0.013-0.116]）和 5-24 h 样本中（0.115[0.029-0.582]）的尿乳果糖/甘露醇比值均升高，这表明肠道通透性增加。尿蔗糖和血浆肠通透素的排泄量无差异。与 HV 相比，AN 患者的血浆总胃饥饿素和去酰化胃饥饿素水平升高，而血浆瘦素浓度降低。此外，αMSH 与 HV 相比保持不变。最后，我们没有观察到总或游离αMSH、瘦素或胃饥饿素反应性 IgG 和 IgM 水平的任何变化，以及它们的亲和力特性。仅观察到酰化胃饥饿素反应性 IgG 的解离常数（kd）略有降低（p=0.0411）。
总之，与 HV 相比，严重营养不良的 AN 患者的肠道通透性更高，但没有证据表明其对调节食欲的肽反应性免疫球蛋白有影响。
