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Dissecting the contribution of host genetics and the microbiome in complex behaviors.
- Source :
-
Cell [Cell] 2021 Apr 01; Vol. 184 (7), pp. 1740-1756.e16. Date of Electronic Publication: 2021 Mar 10. - Publication Year :
- 2021
-
Abstract
- The core symptoms of many neurological disorders have traditionally been thought to be caused by genetic variants affecting brain development and function. However, the gut microbiome, another important source of variation, can also influence specific behaviors. Thus, it is critical to unravel the contributions of host genetic variation, the microbiome, and their interactions to complex behaviors. Unexpectedly, we discovered that different maladaptive behaviors are interdependently regulated by the microbiome and host genes in the Cntnap2 <superscript>-/-</superscript> model for neurodevelopmental disorders. The hyperactivity phenotype of Cntnap2 <superscript>-/-</superscript> mice is caused by host genetics, whereas the social-behavior phenotype is mediated by the gut microbiome. Interestingly, specific microbial intervention selectively rescued the social deficits in Cntnap2 <superscript>-/-</superscript> mice through upregulation of metabolites in the tetrahydrobiopterin synthesis pathway. Our findings that behavioral abnormalities could have distinct origins (host genetic versus microbial) may change the way we think about neurological disorders and how to treat them.<br />Competing Interests: Declaration of interests A patent application related to the role of L. reuteri on social behavior has been filed by BCM. Findings regarding the manipulation of endogenous biotperin levels by the microbiome are the subject of a provisional patent application owned by BCM. M.C.-M. is a scientific co-founder of Mirkrovia. The authors declare no other competing interests.<br /> (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Bacteria classification
Bacteria genetics
Bacteria isolation & purification
Biopterins analogs & derivatives
Biopterins metabolism
Disease Models, Animal
Excitatory Postsynaptic Potentials
Fecal Microbiota Transplantation
Feces microbiology
Limosilactobacillus reuteri metabolism
Limosilactobacillus reuteri physiology
Membrane Proteins deficiency
Membrane Proteins genetics
Mice
Mice, Inbred C57BL
Mice, Knockout
Nerve Tissue Proteins deficiency
Nerve Tissue Proteins genetics
Neurodevelopmental Disorders genetics
Neurodevelopmental Disorders microbiology
Neurodevelopmental Disorders pathology
Neurodevelopmental Disorders therapy
Principal Component Analysis
Psychomotor Agitation pathology
Synaptic Transmission
Gastrointestinal Microbiome
Locomotion
Social Behavior
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4172
- Volume :
- 184
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Cell
- Publication Type :
- Academic Journal
- Accession number :
- 33705688
- Full Text :
- https://doi.org/10.1016/j.cell.2021.02.009