Background Inhibitory control (IC) is critical to keep long-term goals in everyday life. Bidirectional relationships between IC deficits and obesity are behind unhealthy eating and physical exercise habits. Methods We studied gut microbiome composition and functionality, and plasma and faecal metabolomics in association with cognitive tests evaluating inhibitory control (Stroop test) and brain structure in a discovery (n=156), both cross-sectionally and longitudinally, and in an independent replication cohort (n=970). Faecal microbiota transplantation (FMT) in mice evaluated the impact on reversal learning and medial prefrontal cortex (mPFC) transcriptomics. Results An interplay among IC, brain structure (in humans) and mPFC transcriptomics (in mice), plasma/faecal metabolomics and the gut metagenome was found. Obesity-dependent alterations in one-carbon metabolism, tryptophan and histidine pathways were associated with IC in the two independent cohorts. Bacterial functions linked to one-carbon metabolism ( thyX,dut, exodeoxyribonuclease V), and the anterior cingulate cortex volume were associated with IC, cross-sectionally and longitudinally. FMT from individuals with obesity led to alterations in mice reversal learning. In an independent FMT experiment, human donor’s bacterial functions related to IC deficits were associated with mPFC expression of one-carbon metabolism-related genes of recipient’s mice. Conclusion These results highlight the importance of targeting obesity-related impulsive behaviour through the induction of gut microbiota shifts. All data relevant to the study are included in the article or uploaded as supplementary information.

中文翻译：

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肥胖相关的抑制性控制缺陷通过单碳和芳香族氨基酸代谢途径的肠道微生物群变化被表型复制到小鼠身上

背景抑制控制 (IC) 对于在日常生活中保持长期目标至关重要。IC 缺陷和肥胖之间的双向关系是不健康饮食和体育锻炼习惯的背后原因。方法 我们研究了肠道微生物组的组成和功能，以及血浆和粪便代谢组学与评估抑制控制（Stroop 测试）和大脑结构的认知测试（n=156），包括横断面和纵向以及独立复制队列（n = 970）。小鼠粪便微生物群移植 (FMT) 评估了对逆转学习和内侧前额叶皮层 (mPFC) 转录组学的影响。结果发现 IC、大脑结构（人类）和 mPFC 转录组学（小鼠）、血浆/粪便代谢组学和肠道宏基因组之间存在相互作用。在两个独立队列中，单碳代谢、色氨酸和组氨酸途径的肥胖依赖性改变与 IC 相关。与单碳代谢相关的细菌功能（thyX,dut, exodeoxyribonuclease V）和前扣带回皮层体积与横断面和纵向的 IC 相关。来自肥胖个体的 FMT 导致小鼠逆转学习的改变。在一项独立的 FMT 实验中，人类供体与 IC 缺陷相关的细菌功能与受体小鼠的单碳代谢相关基因的 mPFC 表达有关。结论这些结果强调了通过诱导肠道微生物群变化来针对肥胖相关的冲动行为的重要性。所有与研究相关的数据都包含在文章中或作为补充信息上传。