Intestinal permeability and appetite regulating peptides-reactive immunoglobulins in severely malnourished women with anorexia nervosa

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. Methods: 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(2)) to healthy volunteers (HV, n = 34; 26 [23 -35] y; 22.3 [20.6-23.6] kg/m(2)). Results: 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, alpha MSH remained unchanged compared to HV. Finally, we did not observe any modification of the levels of total or free alpha MSH, 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). Conclusions: 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. (C) 2022 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.