Supplementary Material for: Long-term dynamics of serum α-MSH and α-MSH-binding immunoglobulins with a link to gut microbiota composition in patients with anorexia nervosa

Introduction. Immunoglobulins (Ig) reactive with α-melanocyte-stimulating hormone (α-MSH), an anorexigenic neuropeptide, are present in humans and were previously associated with eating disorders. In this longitudinal study involving patients with anorexia nervosa (AN), we determined whether α-MSH in serum is bound to IgG and analyzed long-term dynamics of both α-MSH peptide and α-MSH-reactive Ig in relation to changes in BMI and gut microbiota composition. Methods. The study included 64 adolescents with a restrictive form of AN, whose serum samples were collected at hospital admission, discharge, and during a 1-year follow-up visit, and 41 healthy controls, all females. Results. We found that in both study groups, approximately 40% of serum α-MSH was reversibly bound to IgG and that levels of α-MSH-reactive IgG, but not of α-MSH peptide in patients with AN were low at hospital admission, but recovered 1-year later. Total IgG levels were also low at admission. Moreover, BMI-standard deviation score (SDS) correlated positively with α-MSH IgG in both groups studied, but negatively with α-MSH peptide only in controls. Significant correlations between the abundance of specific bacterial taxa in the gut microbiota and α-MSH peptide and IgG levels were found in both study groups, but they were more frequent in controls. Conclusion/Discussion. We conclude that IgG in the blood plays a role as an α-MSH binding protein, whose characteristics are associated with BMI in both patients with AN and controls. Furthermore, the study suggests that low production of α-MSH-reactive IgG during the starvation phase in patients with AN may be related to altered gut microbiota composition.

引言。与α-促黑素细胞激素（α-melanocyte-stimulating hormone, α-MSH）——一种厌食性神经肽——结合的免疫球蛋白（Immunoglobulins, Ig）在人体中存在，且既往研究显示其与进食障碍相关。本项针对神经性厌食症（Anorexia Nervosa, AN）患者的纵向研究，旨在明确血清中α-MSH是否与免疫球蛋白G（Immunoglobulin G, IgG）结合，并分析α-MSH肽段及抗α-MSH反应性IgG的长期动态变化，及其与体质量指数（Body Mass Index, BMI）和肠道菌群组成的关联。
方法。本研究纳入64例女性限制性神经性厌食症青少年患者，分别于入院时、出院时及1年随访访视时采集血清样本；同时纳入41例女性健康对照。
结果。本研究发现，在两个研究队列中，约40%的血清α-MSH可与IgG发生可逆性结合；神经性厌食症患者入院时的抗α-MSH反应性IgG水平较低，但在1年随访时恢复至正常水平，而其血清α-MSH肽段水平无此变化。患者入院时的总IgG水平同样偏低。此外，在两个研究队列中，体质量指数标准差评分（BMI-standard deviation score, SDS）均与抗α-MSH反应性IgG水平呈正相关，但仅在健康对照队列中，α-MSH肽段水平与SDS呈负相关。两个队列均观察到肠道菌群中特定细菌类群的丰度与α-MSH肽段及IgG水平存在显著相关性，但该类相关性在健康对照队列中更为多见。
结论与讨论。本研究证实，血液中的IgG可作为α-MSH的结合蛋白，其相关特征在神经性厌食症患者及健康对照中均与BMI相关。此外，本研究提示，神经性厌食症患者在饥饿阶段抗α-MSH反应性IgG生成不足，可能与肠道菌群组成改变有关。