The bacteriome and virome in social and stress-related disorders

Simple item page
dc.check.date2025-09-30
dc.contributor.advisorCryan, John
dc.contributor.advisorDinan, Timothy G.
dc.contributor.authorRitz, Nathaniel L.en
dc.contributor.funderScience Foundation Irelanden
dc.date.accessioned2024-06-04T11:52:36Z
dc.date.available2024-06-04T11:52:36Z
dc.date.issued2023
dc.date.submitted2023
dc.description.abstractThe gastrointestinal microbiota has been shown to influence mammalian health and well-being in many conditions but has also been implicated in a variety of diseases and disorders. The multi-faceted interaction of the microbiota with the host that affects the brain and behaviour is termed the microbiota-gut-brain axis. While this axis plays an important role in stress and social behaviour, research has largely focused on associations with the bacterial fraction of the community. The gut also harbours viruses, fungi, archaea, and other microbial forms of life that can affect the health of the mammalian host. Gut viruses, which are dominated by bacteriophages, are also ubiquitous in the gut and have the ability to infect bacteria and alter their structure and activity. Moreover, these populations of viruses are intimately associated with the bacterial community, but little is known about their involvement within the microbiota-gut-brain axis. Whether bacteriophages are capable of exerting effects on the brain and behaviour is largely unknown. To this end, we tested whether the virome was affected by stress followed by the capability of the virome to prevent stress-related sequelae. We found that the virome is stress sensitive and that restoring the virome to mice undergoing stress reduced anxiety-like behaviour, immune activation, inflammation, and gene expression in the brain. These data provide evidence that the gut virome can be harnessed to improve stress-coping outcomes. Social diseases and disorders have been implicated in the microbiota-gut-brain axis. Social anxiety disorder is a common but understudied psychiatric condition. Whether specific microbiota communities play a role in social fear responsivity or are capable of driving social fear behaviour is also unknown. Preclinical animal models of social fear allow for testing translational hypotheses that can then be returned to the clinic. We sought to characterize associations of the microbiota with social fear resiliency and susceptibility. Then, we transferred microbiota from individuals with social anxiety disorder to mice to test whether the microbiota played a causative role in the disorder. We found a strong correlation between microbiota and social fear variability along with differential expression of amygdalar genes involved in social behaviour, immunity, and host-microbe interaction. We also found that microbiota from individuals with social anxiety disorder could drive social fear sensitivity in mice. Mice that received microbiota from social anxiety disorder donors also had impaired cytokine release in the gut, reduced immune cell populations in the mesenteric lymph nodes and circulation, altered basal HPA axis, and diminished oxytocin and oxytocin-related expression of genes in the brain. These data indicate that social fear and anxiety are linked with the microbiota and that the gut-brain axis is a target for future research for social anxiety disorder therapeutics. Herein we tested whether gut viruses could alter stress response, whether social fear behaviour is associated with differential microbial communities, and whether human microbiota from individuals with social anxiety disorder can drive social fear behaviour in the mouse. Collectively we have shown that stress-related sequelae can be restored by virome transfer and that the microbiota can play a causal role in social anxiety disorder.en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationRitz, N. L. 2023. The bacteriome and virome in social and stress-related disorders. PhD Thesis, University College Cork.
dc.identifier.endpage265
dc.identifier.urihttps://hdl.handle.net/10468/15971
dc.language.isoenen
dc.publisherUniversity College Corken
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/
dc.rights© 2023, Nathaniel Lloyd Ritz.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectMicrobiome
dc.subjectMicrobiota-gut-brain axis
dc.subjectFaecal virome transplant
dc.subjectSocial anxiety disorder
dc.subjectSocial fear conditioning
dc.subjectBacteriophage
dc.subjectFaecal microbiota transplant
dc.titleThe bacteriome and virome in social and stress-related disorders
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD - Doctor of Philosophyen
Files
Original bundle
Now showing 1 - 3 of 3
Thumbnail Image
Name:
RitzNL_PhD2023.docx
Size:
12.79 MB
Format:
Microsoft Word XML
Description:
Full Text E-thesis (Word)
Thumbnail Image
Name:
RitzNL_PhD2023.pdf
Size:
12.33 MB
Format:
Adobe Portable Document Format
Description:
Full Text E-thesis
Thumbnail Image
Name:
RitzNL_Submission for Examination Form.pdf
Size:
2.06 MB
Format:
Adobe Portable Document Format
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
5.2 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Research Theses
Anatomy and Neuroscience - Doctoral Theses
APC Microbiome Ireland - Doctoral Theses
College of Medicine and Health - Doctoral Theses
College of Science, Engineering and Food Science - Doctoral Theses