Multivariate associative patterns between the gut microbiota and large-scale brain network connectivity

Gut Microbes. 2021 Jan-Dec;13(1):2006586. doi: 10.1080/19490976.2021.2006586.

Abstract

Research on the gut-brain axis has accelerated substantially over the course of the last years. Many reviews have outlined the important implications of understanding the relation of the gut microbiota with human brain function and behavior. One substantial drawback in integrating gut microbiome and brain data is the lack of integrative multivariate approaches that enable capturing variance in both modalities simultaneously. To address this issue, we applied a linked independent component analysis (LICA) to microbiota and brain connectivity data.We analyzed data from 58 healthy females (mean age = 21.5 years). Magnetic Resonance Imaging data were acquired using resting state functional imaging data. The assessment of gut microbial composition from feces was based on sequencing of the V4 16S rRNA gene region. We used the LICA model to simultaneously factorize the subjects' large-scale brain networks and microbiome relative abundance data into 10 independent components of spatial and abundance variation.LICA decomposition resulted in four components with non-marginal contribution of the microbiota data. The default mode network featured strongly in three components, whereas the two-lateralized fronto-parietal attention networks contributed to one component. The executive-control (with the default mode) network was associated to another component. We found that the abundance of Prevotella genus was associated with the strength of expression of all networks, whereas Bifidobacterium was associated with the default mode and frontoparietal-attention networks.We provide the first exploratory evidence for multivariate associative patterns between the gut microbiota and brain network connectivity in healthy humans considering the complexity of both systems.

Keywords: Bifidobacterium; Linked ICA; Prevotella; brain connectivity networks; fMRI; gut microbiota; resting state.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bifidobacterium / isolation & purification
  • Bifidobacterium / physiology
  • Brain / diagnostic imaging
  • Brain / physiology*
  • Brain-Gut Axis / physiology
  • Female
  • Gastrointestinal Microbiome / genetics
  • Gastrointestinal Microbiome / physiology*
  • Healthy Volunteers
  • Humans
  • Magnetic Resonance Imaging
  • Nerve Net / diagnostic imaging
  • Nerve Net / physiology*
  • Prevotella / isolation & purification
  • Prevotella / physiology
  • Rest / physiology
  • Young Adult

Grants and funding

The study was supported by the Dutch Ministry of Economic Affairs under the TKI Life Science and Health, project LSHM15034. CB and AL have received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777394 for the project AIMS-2-TRIALS. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation program and EFPIA and AUTISM SPEAKS, Autistica, SFARI. This work was further supported by the European Union Horizon2020 program CANDY (Grant Agreement No. 847818). EA received funding from the European Research Council (ERC_StG2019_852189). JST and AAV have received support from the European Union’s Horizon 2020 research and innovation program under Grant Agreement No. 728018 (Eat2beNICE);Autism Speaks European Federation of Pharmaceutical Industries and Associations Simons Foundation Autism Research Initiative