How Lactobacillus reuteri protects against enteropathogenic E. coli infection in the human gut

Dr Stephanie Schuller

Dr Stephanie Schuller

Research on improving food safety is an integral part of the GHFS Programme, which focusses on some of the major foodborne bacterial pathogens including E. coli. Dr Stephanie Schüller is a Lecturer in Infection & Immunity at the University of East Anglia (UEA) and a GHFS Research Leader.  Below, Stephanie blogs about a newly published study in the journal Frontiers in Microbiology.

“Enteropathogenic E. coli (EPEC) is a major foodborne bacterium in developing countries and the second most common cause (after rotavirus) of diarrheal infant death in the world. One of the major virulence traits of EPEC is its ability to tightly adhere to the epithelium of the small intestine by forming characteristic attaching/effacing lesions.

Clinical studies have shown that probiotic bacteria such as lactobacilli can protect against intestinal infection. In particular, Lactobacillus reuteri, a natural inhabitant of the gastrointestinal tract of many mammals and birds, has recently been shown to protect against EPEC infection in infants. Several mechanisms of how probiotic bacteria protect against pathogens have been suggested, and competition for binding sites, also referred to as competitive exclusion, has been the focus of many in vitro studies. However, most of these studies have been performed on human colon cancer-derived cell lines which do not produce a secreted mucus layer. While this approach might be suitable to study the effects of probiotics on inflammatory bowel disease or other conditions with a compromised mucus layer, it remains unknown whether findings on non-mucus producing cell lines can be translated to a normal intestinal mucosa where the epithelium is protected by a thick mucus layer.

False-coloured SEM image showing L. reuteri bacteria (blue) bound to the mucus layer (green) of a human duodenal biopsy. Image taken by lead author Alistair Walsham and coloured by Stephanie Schuller.

False-coloured SEM image showing L. reuteri bacteria (blue) bound to the mucus layer (green) of a human duodenal biopsy. Image taken by lead author Alistair Walsham and coloured by Stephanie Schüller.

In this study, which has been conducted in collaboration with Dr Nathalie Juge’s group at IFR and the Gastroenterology Department at NNUH, we have investigated the effect of L. reuteri on EPEC adherence to mucus- and non-mucus-secreting human intestinal epithelial cell lines and human small intestinal biopsies. We found that adherence of L. reuteri to human intestinal epithelium was strain-specific, and the mucus-binding proteins CmbA and MUB (characterised previously by Dr Juge’s group) increased binding to both mucus-producing and mucus-deficient cell lines. Further studies with two selected isolates demonstrated that L. reuteri can reduce EPEC infection by several mechanisms which include competitive exclusion at the mucus or epithelial level or via potential inhibition of EPEC microcolony dispersal and cell-to-cell spread. These effects were strain-specific and dependent on the intestinal model system used, highlighting the need for a careful choice of experimental models when selecting potential probiotic strains. Alterations in the mucus layer have been reported in a number of infectious and inflammatory diseases, often facilitating bacterial access to the epithelial surface. Whether individuals present with a healthy or compromised mucus layer may therefore influence the rationale for selecting specific probiotic strains.”

Written by Dr Stephanie Schuller, March 2016

Reference: Walsham A, MacKenzie D, Cook V, Wemyss-Holden S, Hews C, Juge N and Schüller S (2016). Lactobacillus reuteri Inhibition of Enteropathogenic Escherichia coli Adherence to Human Intestinal EpitheliumFront. Microbiol. 7:244. doi:10.3389/fmicb.2016.00244

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The programme receives funding from the BBSRC - Biotechnology and Biological Sciences Research Council and involves leading researchers from the Quadram Institute Bioscience, Imperial College, University of East Anglia and St. Mark's Hospital and Academic Institute

Quadram InstituteImperial College LondonUniversity of East AngliaSt. Mark's Hospital and Academic InstituteBBSRC - Biotechnology and Biological Sciences Research Council