A new project at the Institute of Food Research will look at the mechanisms our bodies use to live in harmony with the trillions of bacteria in our digestive system.

Dr Nathalie Juge

Funding of £421,000 from the Biotechnology and Biological Sciences Research Council (BBSRC) to Dr Nathalie Juge will produce new insights into how we maintain the populations of beneficial bacteria whilst keeping out harmful invaders. Living in harmony with our gut bacteria is crucial to our health and this research could also point to new intervention strategies to reinforce gut health.

The microbial community that lives in our digestive tract, known as the gut microbiota, is made up of 10s of trillions of bacteria, from hundreds of different species. These bacteria help us digest our food, provide essential nutrients, protect from harmful bacteria and have roles in our immune defences – the microbiota is crucial to our health. Changes in the balance of different bacteria in our microbiota have been linked to inflammatory bowel diseases and other conditions. How we maintain our peaceful existence with the gut microbiota, and what triggers the changes isn’t understood.

The answer to this question lies with the cells that line our digestive tract and more specifically the layer of protective mucus these cells produce that covers them, especially in the colon, which is where the bulk of the microbiota lives. This consists of a firm layer that prevents bacteria invading our bodies, and a looser layer that provides a suitable home for the gut bacteria. It is believed that bacteria have developed adhesins on their cell surface which enable them to bind to mucus (1).

mucin

Mucus is made up of large proteins called mucins, which contain a complex array of different sugars. Nathalie Juge’s group at the IFR has recently shown that gut bacteria have mucus-binding proteins (MUBs) on their surface (1, 2, 3). The new funding will allow Nathalie’s group to further investigate exactly what in the mucus the MUBs bind to, or what confers specificity into this interaction. The project will focus on Lactobacillus reuteri (4, 5), as a model organism to dissect the impact of MUB on the ability of the bacteria to bind to and influence  host responses.

New techniques developed at the IFR will help identify which mucin sugars are involved in the interaction with MUB proteins in bacteria (6, 7). A variety of molecular  and biochemical techniques will also be used to analyse the MUBs in more detail to understand what it is in their structure that is responsible for interactions with the mucus layer. Also within the mucus layer are antibodies, so the project will look at how MUBs interact with these and how this links into the immune system response of bacteria harbouring MUBs.

This study will provide the most detailed information on how our bodies maintain a beneficial relationship with gut bacteria that is so important to our health, and point to new treatments such as probiotics for when this bacterial balance goes wrong.

This new project builds on some of the research carried out by Dr Faye Jeffers as part of her PhD studentship under the supervision of Dr Nathalie Juge. As well as publishing papers, Faye presented her study at the Set for Britain Poster Competition at the House of Commons.
This article is one of a series highlighting the work of IFR’s excellent PhD students who received their Doctorates at UEA’s congregation ceremony in July 2013.

References:

1.  Juge N.  Microbial adhesins to gastrointestinal mucus. Trends Microbiol. 2012 Jan;20(1):30-9.
2.  Mackenzie DA, Jeffers F, Parker ML, Vibert-Vallet A, Bongaerts RJ, Roos S, Walter J, Juge N. Strain-specific diversity of mucus-binding proteins in the adhesion and aggregation properties of Lactobacillus reuteri. Microbiology. 2010 Nov;156(Pt 11):3368-78.
3.  MacKenzie DA, Tailford LE, Hemmings AM, Juge N. Crystal structure of a mucus-binding protein repeat reveals an unexpected functional immunoglobulin binding activity. J Biol Chem. 2009 Nov 20;284(47):32444-53.
4.  Heavens D, Tailford LE, Crossman L, Jeffers F, Mackenzie DA, Caccamo M, Juge N. Genome sequence of the vertebrate gut symbiont Lactobacillus reuteri ATCC 53608. J Bacteriol. 2011 Aug;193(15):4015-6.
5.  Frese SA, Benson AK, Tannock GW, Loach DM, Kim J, Zhang M, Oh PL, Heng NC, Patil PB, Juge N, Mackenzie DA, Pearson BM, Lapidus A, Dalin E, Tice H, Goltsman E, Land M, Hauser L, Ivanova N, Kyrpides NC, Walter J. The evolution of host specialization in the vertebrate gut symbiont Lactobacillus reuteri. PLoS Genet. 2011 Feb;7(2):e1001314.
6.  Gunning AP, Kirby AR, Fuell C, Pin C, Tailford LE, Juge N. Mining the “glycocode”–exploring the spatial distribution of glycans in gastrointestinal mucin using force spectroscopy. FASEB J. 2013 Jun;27(6):2342-54.
7.  Jeffers F, Fuell C, Tailford LE, Mackenzie DA, Bongaerts RJ, Juge N. Mucin-lectin interactions assessed by flow cytometry. Carbohydr Res. 2010 Jul 2;345(10):1486-91