Kooij Karlijn L, Andreani Nadia Andrea, Keller Lara, Trinh Stefanie, van der Gun Luna, Hak Jamie, Garner Keith, Luijendijk Mieneke, Drost Lisa, Danner Unna, van Elburg Annemarie, Dempfle Astrid, Seitz Jochen, Herpertz-Dahlmann Beate, Baines John F, Adan Roger A H
UMC Brain Center, Department of Translational Neuroscience, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Altrecht Eating Disorders Rintveld, Zeist, the Netherlands.
Int J Eat Disord. 2025 Aug;58(8):1487-1498. doi: 10.1002/eat.24452. Epub 2025 May 2.
Anorexia nervosa (AN) is a complex psychiatric disorder characterized by persistent dieting and reduced food intake, leading to significantly low body weight. Dysbiosis in the gut microbiome of patients with AN has been suggested to contribute to the pathogenesis. Here, we used fecal microbiota transplantation (FMT) in the activity-based anorexia (ABA) rat model to investigate the impact of AN-associated gut microbiota on disease-related outcomes.
We validated the FMT in 12 Wistar rats by depleting the gut microbiome with antibiotics and transplanting two donors' fecal samples. We then transplanted fecal samples from four patients with AN or four healthy controls in 48 rats just before the ABA model exposure and included an antibiotic-only control group. During ABA, the rats had access to a running wheel and only 1.5 h access to chow for 7 days. We monitored body weight, body temperature, food intake, wheel revolutions, and gut microbiome biodiversity and composition.
The antibiotic treatment significantly depleted the rats' gut microbiome and subsequent transplantation made the rats' microbiome more similar to the donors' microbiome. The antibiotic-only group showed reduced survival, as well as lower body weight and temperature during ABA. Transplanted microbiota from patients with AN and healthy controls improved outcomes in the ABA model.
We do not find evidence that the microbiome of patients with AN differentially contributes to anorexia-like phenotypes based upon partial microbiome transplantation. However, the presence of a microbiome impacts the outcome of the ABA model.
神经性厌食症(AN)是一种复杂的精神疾病,其特征为持续节食和食物摄入量减少,导致体重显著降低。有研究表明,AN患者肠道微生物群失调有助于其发病机制。在此,我们在基于活动的厌食症(ABA)大鼠模型中使用粪便微生物群移植(FMT)来研究与AN相关的肠道微生物群对疾病相关结果的影响。
我们通过用抗生素清除肠道微生物群并移植两个供体的粪便样本,在12只Wistar大鼠中验证了FMT。然后,在ABA模型暴露前,我们将来自4名AN患者或4名健康对照的粪便样本移植到48只大鼠中,并设立了仅使用抗生素的对照组。在ABA期间,大鼠可以使用跑步轮,并且在7天内只有1.5小时的进食时间。我们监测了体重、体温、食物摄入量、转轮次数以及肠道微生物群的生物多样性和组成。
抗生素治疗显著耗尽了大鼠的肠道微生物群,随后的移植使大鼠的微生物群与供体的微生物群更加相似。仅使用抗生素的组在ABA期间存活率降低,体重和体温也较低。移植来自AN患者和健康对照的微生物群改善了ABA模型中的结果。
基于部分微生物群移植,我们没有发现证据表明AN患者的微生物群对厌食样表型有不同的影响。然而,微生物群的存在会影响ABA模型的结果。