Infusion of donor feces affects the gut-brain axis in humans with metabolic syndrome.,Molecular Metabolism

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Infusion of donor feces affects the gut-brain axis in humans with metabolic syndrome.
Molecular Metabolism ( IF 7.0 ) Pub Date : 2020-09-08 , DOI: 10.1016/j.molmet.2020.101076
Annick V Hartstra ₁ , Valentina Schüppel ₂ , Sultan Imangaliyev ₁ , Anouk Schrantee ₃ , Andrei Prodan ₁ , Didier Collard ₁ , Evgeni Levin ₁ , Geesje Dallinga-Thie ₁ , Mariette T Ackermans ₄ , Maaike Winkelmeijer ₁ , Stefan R Havik ₁ , Amira Metwaly ₂ , Ilias Lagkouvardos ₅ , Anika Nier ₆ , Ina Bergheim ₆ , Mathias Heikenwalder ₇ , Andreas Dunkel ₈ , Aart J Nederveen ₃ , Gerhard Liebisch ₉ , Giulia Mancano ₁₀ , Sandrine P Claus ₁₀ , Alfonso Benítez-Páez ₁₁ , Susanne E la Fleur ₄ , Jacques J Bergman ₁₂ , Victor Gerdes ₁ , Yolanda Sanz ₁₁ , Jan Booij ₃ , Elles Kemper ₁₃ , Albert K Groen ₁ , Mireille J Serlie ₁₄ , Dirk Haller ₁₅ , Max Nieuwdorp ₁

Affiliation

Department of Internal and Vascular Medicine, Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands.
Chair of Nutrition and Immunology, Technical University of Munich, Freising, Germany.
Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands.
Laboratory of Endocrinology, Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands.
ZIEL-Institute for Food and Health, Technical University of Munich, Freising, Germany.
Department of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, Austria.
German Cancer Research Center (DKFZ), Division of Chronic Inflammation and Cancer, Heidelberg, Germany.
Leibniz-Institute for Food Systems Biology, Technical University of Munich, Freising, Germany.
Department of Laboratory Medicine, University of Regensburg, Regensburg, Germany.
Department of Food and Nutritional Sciences, University of Reading, Reading, United Kingdom.
Institute of Agrochemistry and Food Technology, Spanish National Research Council (IATA-CSIC), Valencia, Spain.
Department of Gastroenterology, Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands.
Department of Clinical Pharmacy, Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands.
Department of Endocrinology and Metabolism, Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands.
Chair of Nutrition and Immunology, Technical University of Munich, Freising, Germany; ZIEL-Institute for Food and Health, Technical University of Munich, Freising, Germany.

Objective

Increasing evidence indicates that intestinal microbiota play a role in diverse metabolic processes via intestinal butyrate production. Human bariatric surgery data suggest that the gut-brain axis is also involved in this process, but the underlying mechanisms remain unknown.

Methods

We compared the effect of fecal microbiota transfer (FMT) from post-Roux-en-Y gastric bypass (RYGB) donors vs oral butyrate supplementation on (¹²³I-FP-CIT-determined) brain dopamine transporter (DAT) and serotonin transporter (SERT) binding as well as stable isotope-determined insulin sensitivity at baseline and after 4 weeks in 24 male and female treatment-naïve metabolic syndrome subjects. Plasma metabolites and fecal microbiota were also determined at these time points.

Results

We observed an increase in brain DAT after donor FMT compared to oral butyrate that reduced this binding. However, no effect on body weight and insulin sensitivity was demonstrated after post-RYGB donor feces transfer in humans with metabolic syndrome. Increases in fecal levels of Bacteroides uniformis were significantly associated with an increase in DAT, whereas increases in Prevotella spp. showed an inverse association. Changes in the plasma metabolites glycine, betaine, methionine, and lysine (associated with the S-adenosylmethionine cycle) were also associated with altered striatal DAT expression.

Conclusions

Although more and larger studies are needed, our data suggest a potential gut microbiota-driven modulation of brain dopamine and serotonin transporters in human subjects with obese metabolic syndrome. These data also suggest the presence of a gut-brain axis in humans that can be modulated.

NTR registration

4488.

中文翻译：

捐赠者粪便的输注会影响患有代谢综合征的人的肠脑轴。

客观的

越来越多的证据表明肠道微生物群通过肠道丁酸盐的产生在多种代谢过程中发挥作用。人类减肥手术数据表明，肠-脑轴也参与了这一过程，但其潜在机制仍不清楚。

方法

我们比较了来自 Roux-en-Y 胃绕道手术 (RYGB) 供体后的粪便微生物群转移 (FMT) 与口服丁酸盐补充剂对 ( ¹²³ I-FP-CIT 确定的) 脑多巴胺转运蛋白 (DAT) 和血清素转运蛋白 (DAT) 的影响。 SERT）结合以及稳定同位素确定的基线和 4 周后 24 名未接受治疗的男性和女性代谢综合征受试者的胰岛素敏感性。在这些时间点还测定了血浆代谢物和粪便微生物群。

结果

我们观察到，与口服丁酸盐相比，供体 FMT 后大脑 DAT 有所增加，从而减少了这种结合。然而，在代谢综合征患者中进行 RYGB 供体粪便移植后，对体重和胰岛素敏感性没有影响。粪便中统一拟杆菌水平的增加与 DAT 的增加显着相关，而普雷沃菌属的增加则与 DAT 的增加显着相关。表现出逆相关关系。血浆代谢物甘氨酸、甜菜碱、蛋氨酸和赖氨酸（与S-腺苷甲硫氨酸循环相关）的变化也与纹状体 DAT 表达的改变有关。