Vatche and Tamar Manoukian Division of Digestive Diseases, Los Angeles, USA.
UCLA Microbiome Center, Los Angeles, USA.
Sci Rep. 2023 Apr 4;13(1):5488. doi: 10.1038/s41598-023-32713-2.
A growing body of preclinical and clinical literature suggests that brain-gut-microbiota interactions may contribute to obesity pathogenesis. In this study, we use a machine learning approach to leverage the enormous amount of microstructural neuroimaging and fecal metabolomic data to better understand key drivers of the obese compared to overweight phenotype. Our findings reveal that although gut-derived factors play a role in this distinction, it is primarily brain-directed changes that differentiate obese from overweight individuals. Of the key gut metabolites that emerged from our model, many are likely at least in part derived or influenced by the gut-microbiota, including some amino-acid derivatives. Remarkably, key regions outside of the central nervous system extended reward network emerged as important differentiators, suggesting a role for previously unexplored neural pathways in the pathogenesis of obesity.
越来越多的临床前和临床文献表明，脑-肠-微生物群相互作用可能有助于肥胖的发病机制。在这项研究中，我们使用机器学习方法利用大量的微观结构神经影像学和粪便代谢组学数据，更好地了解肥胖与超重表型的关键驱动因素。我们的研究结果表明，尽管肠道来源的因素在这一区别中起作用，但区分肥胖和超重个体的主要是大脑导向的变化。在我们的模型中出现的关键肠道代谢物中，许多可能至少部分来源于或受肠道微生物群的影响，包括一些氨基酸衍生物。值得注意的是，中枢神经系统外的关键奖励网络区域作为重要的区分因素出现，这表明以前未被探索的神经通路在肥胖的发病机制中可能起作用。
