30 Mar Immune System Uses Mucous To Anchor Desired Bacteria to Intestine

MedicalResearch.com Interview with:

Dr. Jonas Schluter

Jonas Schluter, DPhil
Memorial Sloan Kettering Cancer Center
New York City

Dr. Kirstie McLoughlin

Kirstie McLoughlin
Department of Zoology
Oxford University 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Microbes in our guts perform many important functions for our health. Healthy individuals are inhabited by a complex microbial community. A less diverse community is often a sign of ill health, and can be accompanied by loss of beneficial functions that a normal microbial community provides for the host.

We try to understand how such complex communities can persist – after all, competition between microbes could lead to the eradication of slow-growing, but helpful microbes. We built a computer model of the gut that allows us to simulate how the host can actively help such slow microbes, and thereby maintain a healthily diverse microbial community. We show that a mechanism by which the host can achieve such selection is via secretions that help slow growing microbes persist by sticking in place.

We propose that the host can change microbiota composition by conveying increased adhesion to disadvantages microbes, for example using mucus molecules and the attached sugars such as fucose. We hypothesise that this might also help explain the secretion of vast amounts of immune system molecules such as immunoglobulin A – perhaps they are not only a way to harm, but also to help certain microbes by anchoring them to the mucus. Indeed, we demonstrate that the host can change the selective effect of increased adhesion by tuning the mucus secretion rate: from beneficial for the adhered microbes at low mucus flow to detrimental at high mucus secretion rates.

MedicalResearch.com: What should clinicians and patients take away from your report?

Response:  Microbes in our gut form a complicated ecosystem where competition between microbial species is fierce. We know that hosts actively influence this competition, both by helping and by harming microbial species selectively. We built a computational model that is both complex enough to predict new biological insight, and tractable enough so that we can really understand everything that is going on. This allows us to rapidly test hypotheses – though it is also only a first step and in vivo studies need to follow in order to test our model’s predictions.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: As we discuss in the paper, there is already some evidence for that host secretions to increase microbial adhesion, and that this can provide an advantage for the microbes in question. Specific experiments designed to test the hypothesis (that host provided adhesion can provide a selective benefit to disadvantaged microbes) proposed by our paper in vivo or in vitro would be the next step. Further, a corollary of our model is that decreasing adhesiveness of microbes could be used as a selective mechanism working in the opposite direction. It would, therefore, be interesting to identify the effect of host secreted molecules on adhesion, and to systematically categorise them by their effect on the affected microbes. 

MedicalResearch.com: Is there anything else you would like to add?

Response: We hope to showcase the value of systems biology approaches to the field of immunology and gut microbiota research. Rigorous modelling allows us to combine a range of immunological and biological findings, which taken together can yield mechanistic insights to spark ideas for future empirical studies.  

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Kirstie McLoughlin, Jonas Schluter, Seth Rakoff-Nahoum, Adrian L. Smith, Kevin R. Foster. Host Selection of Microbiota via Differential Adhesion. Cell Host & Microbe, 2016; DOI: 10.1016/j.chom.2016.02.021

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More Medical Research Interviews on MedicalResearch.com

Dr. Jonas Schluter and Kirstie McLoughlin (2016). Immune System Uses Mucous To Anchor Desired Bacteria to Intestine MedicalResearch.com

Last Updated on March 30, 2016 by Marie Benz MD FAAD