How do commensal bacteria protect against gut infection? (SCHULLER_F17DTP1)

Lead Research Organisation: University of East Anglia
Department Name: Graduate Office

Abstract

The human body is populated by trillions of commensal bacteria (microbiota), the majority of which reside in the colon. Most bacteria are strictly anaerobic and do not tolerate oxygen. While the human host provides the bacteria with a nutrient-rich environment, the microbiota enhances the metabolism of polysaccharides and produces essential vitamins. In addition, the microbiota protects the host against enteric infections and has a beneficial role in tissue homeostasis and modulation of the immune system. While it is well established how foodborne pathogens interfere with intestinal function, the underlying molecular mechanisms of how the microbiota counteracts these influences remain largely unknown. This is mainly due to a lack of experimental intestinal model systems supporting the survival of anaerobic bacteria.

Here we will assess the impact of pathogen-commensal-host interactions using a Vertical Diffusion Chamber (VDC) system which we have recently developed to allow us to perform co-incubations of human intestinal epithelial cells with bacteria in an anaerobic environment. The aim of this project is to optimise the VDC culture model to support optimal growth and adhesion of gut symbionts, determine the interactions of commensals with the epithelial surface, and investigate the effect of gut commensals on enteropathogenic E. coli-induced epithelial permeability, loss of ion absorption and inflammation.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M011216/1 01/10/2015 31/03/2024
1937469 Studentship BB/M011216/1 01/10/2017 30/09/2021 Conor McGrath
 
Description Through this work a model system of the intestinal epithelium was established using human-derived cell lines. The model system developed allows culture of oxygen-sensitive bacteria alongside a mucus-secreting intestinal epithelium. The model was applied to determine the interactions between human gut pathogens (Enteropathogenic E. coli, EPEC) or commensal organisms (Limosilactobacillis reuteri & Ruminicoccus gnavus) and the host. Results showed enhanced epithelial colonisation of EPEC and R. gnavus with mucus-secreting epithelia versus a non mucus-secreting control. In addition, the immune response to EPEC was also enhanced, as seen by increased secretion of anti-inflammatory cytokine interleukin-8 by the host cells.
Further work investigating the influence of L. reuteri on EPEC growth and colonisation indicated significantly reduced pathogen numbers during co-culture with commensal organisms, which was enhanced in the presence of a mucus-producing epithelium. Co-culture with L. reuteri also reduced IL-8 secretion from EPEC infected epithelia, suggesting anti-inflammatory activity. Corresponding experiments with R. gnavus revealed antagonistic activity against EPEC growth and colonisation, but only in the presence of a mucus-producing epithelium, suggesting that R. gnavus requires interaction with mucus to elicit protective effects against EPEC.
Exploitation Route The model system could be used to study host-microbe interactions or colonisation resistance of the gut microbiota. The protocol used to study inflammatory response to EPEC was developed in-house and may be applied in future studies on immune responses to pathogens. The antagonistic activities demonstrated by the commensals could be studied in more detail, either in a different context (I.e. model system) or to understand the fundamental mechanisms driving them.
Sectors Pharmaceuticals and Medical Biotechnology

 
Description Microbiology Society: Society Conference Grant 2019
Amount £300 (GBP)
Funding ID GA001608 
Organisation Microbiology Society 
Sector Learned Society
Country United Kingdom
Start 06/2019 
End 06/2019