For International Day of Immunology, on Friday 27 April the British Society for Immunology (BSI) teamed up with Nature Research and the Francis Crick Institute to hold a panel discussion on 'How the gut responds to microbes in health and disease'. Hosted by science writer and presenter Vivienne Parry, the panel of five interdisciplinary UK-based scientists discussed how the immune system of the gut responds to its commensal bacteria, and how this can go wrong to cause disease.
The inner tube of life
Professor Fiona Powrie, Director of the Kennedy Institute of Rheumatology at the University of Oxford, opened the discussion by explaining how the human gut, or ‘the inner tube of life’, is constantly exposed to both harmless and pathogenic microbes. In fact, the human gut is home to trillions of generally harmless ‘commensal’ bacteria, which weigh a total of around 1 kilogram. As one audience member asked, “When do we get our microbiota? And where does it come from?”, the panel explained that we receive our first ‘dose’ of microbiota from our mother’s vaginal canal during birth. This, combined with bacteria from skin to skin contact and our surroundings in the first few days of life, makes up the first ‘pioneers’ of the gut microbiota.
Friend versus foe
A key job of the gut immune system is to distinguish between the harmless commensal bacteria and harmful pathogens which can make us sick, such as Salmonella. How does the gut immune system make this decision? Professor Powrie told us how regulatory T cells send out anti-inflammatory signals to stop the immune system responding against commensal bacteria, while leaving it to deal appropriately with pathogenic bacteria.
Another way the gut immune system tolerates commensal bacteria is through the maintenance of a barrier between the contents of the gut. Molecular immunologist and research group leader at the Francis Crick Institute, Professor Gitta Stockinger, described how a physical barrier comprising mucus and the gut epithelium prevents the immune system from detecting most intestinal bacteria – although certain types of immune cells, called dendritic cells, can reach in to the intestinal tract to ‘sample’ bacteria, to make sure there are no pathogens present that require an immune response. She also pointed out that if this barrier is breached, once-harmless commensal bacteria can become pathogenic once in contact with the bloodstream and immune system.
Following on from this, Professor Holm Uhlig, a clinical doctor and researcher into childhood inflammatory bowel disease (IBD) at the Nuffield Department of Medicine, University of Oxford, told us that when the immune system responds inappropriately to our commensal bacteria or food in our guts, we can develop conditions such as IBD or coeliac disease. He stated that genes play a big role in the ability of the gut immune system to tolerate commensal bacteria, and that just one defective gene can result in gut inflammation arising from a loss of tolerance. As it’s impossible to eradicate our commensal bacteria, the only current treatment options are those which suppress or modify the immune system's response to it. Answering an audience question about the collaborative role of scientific researchers and clinicians, Prof Powrie explained that, as a researcher, collaborating with clinicians such as Prof Holm enables her to prioritise research and address important unmet clinical needs. These collaborations are the basis of the development of new drugs which can change patients’ lives.
As well as needing to tolerate commensal bacteria and food, Professor Anne Cooke, Vice President and Chair of Forum at the BSI, then described how the gut immune system may also encounter microscopic intestinal parasitic worms – with a potentially anti-inflammatory effect. She explained that, following the introduction of widespread sanitation in the developed world, intestinal parasitic worms that co-evolved with humans over thousands of years have largely been eradicated from our guts. This has coincided with a rise in inflammatory diseases, such as asthma and multiple sclerosis. Coupled with the fact that the prevalence of inflammatory disease is strikingly lower in developing areas such as Africa where intestinal worms are still common, this led to the development of the hygiene hypothesis which states that a lack of exposure to infectious agents such as bacteria and parasites can lead to a range of inflammatory conditions. Professor Cooke told us that in clinical trials, multiple sclerosis patients reported a reduction in the progression of their disease following the ingestion of live parasitic worm eggs. Although the mechanisms of this are unclear, this indicates that the worm eggs, or worms themselves, may alter immune responses in areas of the body outside the gut.
A nervous disposition?
Dr Vassilis Pachnis, neurologist and research group leader at the Francis Crick Institute went on to describe how the gut immune system and the nervous system were intrinsically linked – and with that, interactions between the gut and microbiota could also affect the workings of the nervous system. He stated that neurotransmitters, as well as talking to other neurons, could also have effects on immune cells – and messages from immune cells could also transmit to neurons. Research shows that experimental animals that reared with no commensal bacteria exhibit alterations in the function of the intestinal nervous system, and that the two systems seem to rely intrinsically upon each other for their functionality.
The panel then fielded a swathe of audience questions, ranging from the benefits of faecal transplants to the potential impacts of gut inflammation on mental health, before Vivienne Parry brought proceedings to a close. Overall, the discussion was thought-provoking and varied, with equal contributions from a highly engaged audience and an accomplished and diverse panel. We would like to thank our collaborators Nature Research and the Francis Crick Institute and all the speakers for making this event possible and look forward to being a part of similar events in the future.
Policy & Public Engagement Officer, British Society for Immunology