Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; Research Center of Clinical Medical Imaging, Anhui Province, Hefei 230032, China; Anhui Provincial Institute of Translational Medicine, Hefei 230032, China.
Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
Prog Neuropsychopharmacol Biol Psychiatry. 2022 Mar 8;113:110468. doi: 10.1016/j.pnpbp.2021.110468. Epub 2021 Nov 2.
Background The field of microbiota-gut-brain research in animals has progressed, while the exact nature of gut microbiota-brain-cognition relationship in humans is not completely elucidated, likely due to small sample sizes and single neuroimaging modality utilized to delineate limited aspects of the brain. We aimed to comprehensively investigate such association in a large sample using multimodal MRI. Methods Fecal samples were collected from 157 healthy young adults and 16S sequencing was used to assess gut microbial diversity and enterotypes. Five brain imaging measures, including regional homogeneity (ReHo) and functional connectivity density (FCD) from resting-state functional MRI, cerebral blood flow (CBF) from arterial spin labeling, gray matter volume (GMV) from structural MRI, and fractional anisotropy (FA) from diffusion tensor imaging, were jointly analyzed with a data-driven multivariate fusion method. Cognition was evaluated by 3-back and digit span tasks. Results We found significant associations of gut microbial diversity with ReHo, FCD, CBF, and GMV within the frontoparietal, default mode and visual networks, as well as with FA in a distributed set of juxtacortical white matter regions. In addition, there were FCD, CBF, GMV, and FA differences between Prevotella- versus Bacteroides-enterotypes in females and between Prevotella- versus Ruminococcaceae-enterotypes in males. Moreover, the identified neuroimaging fusion biomarkers could mediate the associations between microbial diversity and cognition. Conclusions Our findings not only expand existing knowledge of the microbiota-gut-brain axis, but also have potential clinical and translational implications by exposing the gut microbiota as a promising treatment and prevention target for cognitive impairment and related brain disorders.
动物的微生物群-肠道-大脑研究领域已经取得了进展，而人类肠道微生物群-大脑-认知关系的确切性质尚未完全阐明，这可能是由于样本量小和用于描绘大脑有限方面的单一神经影像学模式所致。我们旨在使用多模态 MRI 全面研究大样本中的这种关联。
从 157 名健康年轻成年人中收集粪便样本，并使用 16S 测序评估肠道微生物多样性和肠型。联合使用静息态功能磁共振成像的局部一致性（ReHo）和功能连接密度（FCD）、动脉自旋标记的脑血流（CBF）、结构磁共振的灰质体积（GMV）和扩散张量成像的各向异性分数（FA）等 5 种脑影像学指标，采用数据驱动的多元融合方法进行分析。采用 3 -back 和数字跨度任务评估认知。
我们发现肠道微生物多样性与额顶叶、默认模式和视觉网络内的 ReHo、FCD、CBF 和 GMV 以及皮质下白质区域的 FA 呈显著相关。此外，在女性中，普雷沃氏菌-肠型与拟杆菌-肠型之间存在 FCD、CBF、GMV 和 FA 差异，在男性中，普雷沃氏菌-肠型与瘤胃球菌科-肠型之间存在 FCD、CBF、GMV 和 FA 差异。此外，鉴定出的神经影像学融合生物标志物可以介导微生物多样性与认知之间的关联。
我们的研究结果不仅扩展了微生物群-肠道-大脑轴的现有知识，而且通过暴露微生物群作为认知障碍和相关大脑疾病的有前途的治疗和预防靶点，具有潜在的临床和转化意义。
