Investigating the effect of Bifidobacterium on the host intestinal epithelium in health and disease

Harnisch, Lukas C. (2017) Investigating the effect of Bifidobacterium on the host intestinal epithelium in health and disease. Doctoral thesis, University of East Anglia.

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Abstract

Bifidobacteria are prominent members of the human gastrointestinal tract, particularly in early life. Their presence is generally linked to health, as reduced abundance of bifidobacteria is linked to a range of diseases including, Inflammatory Bowel Disease (IBD). However, how these beneficial microbes modulate host health is currently unclear. The intestinal epithelium barrier is essential for gut health, and previous studies have suggested that Bifidobacterium breve UCC2003 protects intestinal epithelial cells (IECs) from experimental pathological epithelial cell shedding. Thus, I hypothesised that B. breve directly modulates IECs, which is essential for maintaining homeostasis.
Initial studies, probing the role of the mechanosensitive ion channel Piezo1, indicated that this protein may not play a central role within the intestine (utilising zebrafish, and mouse models, and IBD patient biopsies), as had previously been described for the dermis. Furthermore, B. breve did not appear to modulate transcription or translation of Piezo1, suggesting other mechanisms may be involved in IEC regulation. Therefore, I next assessed the global IEC transcriptome (via RNA-seq), and determined that UCC2003 induced distinct responses in neonatal IECs including, TLR2, TLR9, IL-17C, and integrin signalling upregulation, which correlates with this microbe’s ability to protect the epithelial barrier. Furthermore, analysis of the B. breve transcriptome in vivo (both in germ-free, and wild-type mice) highlighted host, and microbial community adaption responses including, bile acid resistance, iron scavenging, and differential nutrient metabolism.
In summary, B. breve UCC2003 induces specific modulation of the IEC transcriptome during homeostatic conditions, which reveals targets for potential disease intervention. Furthermore, distinct B. breve transcription profiles in vivo, also indicate promising microbial factors that may have host/microbiota modulatory effects, that could be targeted for development of new ‘probiotics’. This work contributes novel insight into how bifidobacteria modulate intestinal responses, and supports their use for improving host health and preventing disease.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Stacey Armes
Date Deposited: 24 Aug 2018 11:05
Last Modified: 24 Aug 2018 11:05
URI: https://ueaeprints.uea.ac.uk/id/eprint/68127
DOI:

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