Metabolic and Neural Mechanisms Underlying the Associations Between Gut Bacteroides and Cognition: A Large-Scale Functional Network Connectivity Study

Abstract

There is a proof-of-concept that microbial metabolites provide a molecular connection between the gut and the brain. Extensive research has established a link between gut Bacteroides and human cognition, yet the metabolic and neural mechanisms underlying this association remain largely unknown. Here, we collected fecal samples, resting-state functional MRI, and cognitive data from a large and homogeneous sample of 157 healthy young adults. 16S rRNA gene sequencing was conducted with abundances of Bacteroides and metabolic pathways quantified by species annotation and functional prediction analyses, respectively. Large-scale intra- and internetwork functional connectivity was measured using independent component analysis. Results showed that gut Bacteroides were related to multiple metabolic pathways, which in turn were associated with widespread functional network connectivity. Furthermore, functional network connectivity mediated the associations between some Bacteroides-related metabolic pathways and cognition. Remarkably, arginine and proline metabolism, phenylalanine metabolism, and biosynthesis of unsaturated fatty acids act as the key metabolic pathways that are most contributive, and the executive control and sensorimotor systems contribute most strongly at the neural level. Our findings suggest complex poly-pathway and poly-network processes linking Bacteroides to cognition, more generally yielding a novel conceptualization of targeting gut Bacteroides as an intervention strategy for individuals with cognitive impairment.

Association of food insecurity on gut microbiome and metabolome profiles in a diverse college-based sample

“…However, FI status displayed distinction by having a greater probability of co-occurrence of the select amino acids, including phenylalanine, with Clostridium , Oscillospiraceae , and Ruminococcaceae . Phenylalanine has been identified as a fecal metabolite with a connection to the brain 58 and associated with GM disturbance in major depressive disorder 59 . In contrast, FS individuals had unique co-occurrences with creatine and carnosine, and the glutamic acid derivative, pyroglutamic acid.…”

A mediation analysis of the role of total free fatty acids on pertinence of gut microbiota composition and cognitive function in late life depression

“…In this study, the abundance of 183 bacteria species was detected at the genus level. After reviewing the previous literature, 8 species of bacteria most likely related to cognition and emotion, Bacteroides [ 27 – 29 ] , Prevotella [ 30 – 32 ] , Megamonas [ 33 – 35 ] , Parabacteroides [ 29 , 36 , 37 ] , Ruminococcus [ 37 – 39 ], Faecalibacterium [ 33 , 40 , 41 ] , Bifidobacterium [ 36 , 42 , 43 ], and Akkermansia [ 40 , 44 , 45 ], were included for further analysis.…”

Impact of sex and serum lipids interaction on working memory: A large‐scale brain networks study

“…Spatial ICA separates the participant data into linear mixtures of spatially independent components that exhibit a unique time course profile. Detailed quality control and preprocessing procedures are described in our previous study (Zhang et al., 2021 ). Finally, 14 functional networks out of 26 independent components were obtained (Figure S1 ): anterior and posterior default mode networks (aDMN and pDMN); executive control network (ECN); left and right frontoparietal networks (lFPN and rFPN); salience network (SN); dorsal and ventral attention networks (DAN and VAN); dorsal and ventral sensorimotor networks (dSMN and vSMN); auditory network (AN); and medial, lateral, and posterior visual networks (mVN, lVN, and pVN).…”

“…These functional networks can be automatically identified by independent component analysis (ICA) of rs‐fMRI data, a useful method enabling data‐driven, exploratory investigation of temporal correlations among brain regions at rest (Calhoun et al., 2001 ; van de Ven et al., 2004 ). This approach has been broadly applied to explore the underlying relationships between cognition and large‐scale functional organization (inter‐ and intra‐network FCs) in normal and abnormal brains (Wang et al., 2020 ; Zhang et al., 2021 ). Inter‐network FC reflects the information exchange capability between different regions, whereas intra‐network FC reflects information specialization within specific functional networks (Liao et al., 2017 ).…”