P071 Studying the effects of the probiotic bifidobacteria on gut health and intestinal epithelial cells function

M. Poletti1, I. Hautefort1, A. Treveil1,2, A. Demeter1, E. Rodriguez1, A. Brion2, A. Goldson2, D. Divekar3, Z. Schofield2, I. O’Neill2, A. Lister1, J. Lipscombe1, A. Watson3,4, I. Macaulay1, L. Hall2, T. Korcsmaros1,2

1Earlham Institute, Organisms and Ecosystems, Norwich, UK, 2Quadram Institute Biosciences, Gut microbes and Health, Norwich, UK, 3University of East Anglia, Norwich Medical School, Norwich, UK, 4University of East Anglia, School of Biological Sciences, Norwich, UK


Intestinal homeostasis depends on complex interactions between the microbiota, the intestinal epithelium and the host immune system. Paneth cells play an important role thanks to their release of antimicrobial peptides and their dysfunction has been shown to contribute to Crohn’s disease. The human gut commensal Bifidobacteria has been highlighted as a protective agent in IBD. Whilst the specific modulating factors are largely unidentified, evidence suggests that Bifidobacteria can interact with host intestinal cells. Such interactions can alter host molecular pathways, resulting in a modified intestinal cell function. Understanding these effects is crucial to unravel the potential benefits of bifidobacteria for IBD. In this study, we developed a workflow to investigate the beneficial effects of the probiotic bifidobacteria in modulating gene regulation and function of different intestinal epithelial cells in the gut.


We gavaged either conventionally raised (SPF) or germ-free mice (n = 5) with Bifidobacterium breve UCC2003 (1–5 × 108 CFU), and sorted intestinal epithelial cell types (Lgr5+ stem cells, Paneth cells and transit-amplifying cells) from the mouse intestinal tissue by flow cytometry using a panel of known antibodies. Each isolated cell population (n = 200) was subsequently profiled by low input RNA sequencing and DNA methylation.


Intracellular lysozyme staining for Paneth cells and initial gene expression data exploration suggests successful separation of the different populations from the mouse intestinal tissue using flow cytometry. Gene expression data were further analysed using network biology approaches to generate cell-type-specific molecular regulatory networks indicating genes regulation by bifidobacteria in each cell types. Overlaying the methylation data will elucidate the role of epigenetics played during this regulation. Together, these networks will improve our understanding of how Bifidobacteria affects these different cells types through communication with precursor stem cells and/or with direct effects on the fully differentiated cells, ultimately impacting their function.


In the future, we aim to use a similar workflow using two-dimensional human-derived organoids monolayers co-cultured with bifidobacteria to investigate the effects on host intestinal epithelial cell function in a high-throughput and patient-specific manner. This will increase our understanding of the complex role played by host genetics and microbial factors in the pathogenesis of gastrointestinal diseases such as IBD, and hopefully pave the way for translational developments in the prevention these pathologies.