Our Interview With Dr Marie Lewis
Dr Marie Lewis is a Lecturer in Gut Immunology and Microbiology at the University of Reading. We caught up with her to find out more about her career and research…
1. Can you tell us about your career path, and how you got to your current position as Lecturer in Gut Immunology and Microbiology?
I went the classic route from BSc (University of Bath) to postdoc (University of Bristol) via a PhD University of Exeter) and was appointed as a lecturer at the University of Reading in 2013. However, the focus has shifted from industrial microbial biofilms to mucosal immunology and gut bacteria (the gut microbiota).
2. What led to your interest in the gut microbiota and immunity?
I have always been interested in cell biology and bacteriology. It still amazes me that so much is going on in one minute cell. However, what’s more interesting is how communities of bacteria interact with each other. My PhD was funded by Kodak because all large industrial water tanks and pipelines have microbial communities on their inner surfaces and this leads to all sorts of problems. The bacteria can slough off and be carried further down the processing line, for example, but also microbes in a biofilm behave very differently to bacteria floating around in solution. A biocide might swiftly kill these planktonic bacteria but once they are stuck to a surface and living as part of a community they can become very resistant to the same biocide. It’s not too much of a leap to apply knowledge from biofilms to the gut microbiota which is also a microbial community living on a surface. However, it becomes even more interesting since these gut microbes are not only interacting with each other, but also with their host. It appears that all creatures with a gut host microbial communities inside it which have evolved alongside them. These gut microbes are absolutely necessary for normal growth and development, and can play a key role in health and disease. Gut microbes interact with their host on many levels and have a very important role in developing and maintaining their host’s immune system. I just find the whole thing really interesting and we still have so much to learn about how the microbiota behaves and influences host development, health and disease. We’re certainly not going to run out of things to do before I retire.
3. Can you tell us about the role of the gut bacteria in the development of the immune system, and how important a part it has to play?
Evidence for the importance of the gut microbiota in the development of the immune system primarily comes from germ-free animals. Such animals are born into a sterile environment and remain unexposed to live microbes. These animals are smaller than their ‘normal’ equivalents which are colonised with microbes and have all sorts of strange physiologies, including an under-developed and poorly functioning immune system. We are all born with only a rudimentary immune system and rely on antibodies from our mothers to get through the first few weeks as our own immune systems grow. However, in germ-free animals, immune development doesn’t occur and they remain incredibly susceptible to fatal infections. If these germ-free animals are then exposed to non-pathogenic bacteria, the immune system starts to develop and there is very strong evidence that exposure to microbes is the primary driving force for immune development.
4. You have been involved in lots of research projects, but could you share with us some of the key projects you have been involved in recently and what were the findings?
It was known for some time that growing up on a farm was linked with a reduced likelihood of developing allergies in later life, but cause and effect was unclear.
Was it something on the farm providing protection, or are families with a propensity for allergy development unlikely to live on farms?
We answered this question by rearing piglets on a farm and their siblings in a high-hygiene, but not germ-free, facility. We demonstrated that something on the farm was directly generating gut environments with increased potential for tolerance. Piglets removed from the farm at one-day old lost this potential for immune regulation. We showed that something within a farm environment is directly affecting immune development, although we suspect it is a combination of several factors and not just down to one. We use piglets quite a lot for early-life studies because in addition to their physiological similarities to humans (compared to rodent models), they are born running around and self-sufficient which means the maternal influence can be removed. Using piglets, we demonstrated that the first day of life is a very important time for influencing the gut microbiota and subsequent immune development. We have also shown that factors such as the type of protein received during weaning can affect how probiotics behave, even if that protein hasn’t been in the diet for the past month. Our findings have important implications when it comes to designing trials since early-life events, which occurred before the trial started, are often ignored.
We are currently interested in how dietary iron changes the development of the microbiota and immunity which is important in terms of iron-fortified formula milk given to both infants and piglets. We are also exploring how the development of the immune system and gut microbiota can differ between the sexes. This has important implications when it comes to developing early-life treatments which can modulate the gut microbiota of infant girls and boys in different ways.
5. What does a typical working day look like for you?
I have a very diverse job and there’s no such thing as a typical day. Although I have a rough plan, it soon goes out the window once I’ve opened my emails and had several knocks at the door. I teach undergraduates and master students, and as the department director of PhD student studies, I have an active role in postgraduate training and professional development. Like all academic staff I also have administrative duties and one of mine is running our departmental flow cytometry service. This runs as a business which is accessed by researchers across the university and beyond, and by industrial collaborators.
However, my primary focus is research and I lead several projects. I very much enjoy the initial discussion stages of a project with potential collaborators where we identify ‘the problem’ and design projects to generate evidence to help solve these problems. It’s then a case of managing these projects to ensure we deliver and publish our results. It’s essential to disseminate our findings to other academics and industry with the aim of ensuring the projects lead to real impact. This process often takes several years and projects are often at different stages of the process so multitasking and being able to switch rapidly from one subject to another is essential. But this keeps me on my toes and I prefer to have a lot going on. As a result, my typical day flies past.
6. There are many early life events, such as being born pre-term, delivered via caesarean section, or being formula-fed, which can result in changes to the infant gut microbiota. These are associated with an increased risk of certain conditions, such as obesity and allergic disease. Is there any research to show how we could overcome these microbial differences in infancy, to potentially reduce the risk of associated conditions?
How the immune system develops is crucial to how it functions in later life and this development is triggered by the first wave of microbes which enter and colonise the gut soon after birth. These early colonisers come from the mother and from the immediate environment and change the intestinal microenvironment making it more hospitable or hostile to the bacteria which enter a bit later on. Under normal circumstances these microbes drive the development of an immune system which responds appropriately to challenge. This means responding effectively to clear potentially harmful pathogens and altered ‘self’ cells (pre-cancerous perhaps), whilst ignoring normal ‘self’, harmless antigens and microorganisms and thus preventing autoimmune disease and allergy.
There is evidence starting to emerge that specific probiotics and prebiotics could have beneficial effects for such infants, but it is a complex field and we don’t yet fully understand the links between the early microbiota and the development of an appropriately functioning immune system in later life. Although an intervention might be of benefit to one aspect of immunity, it could also promote immune behaviour which is less desirable. For example, an intervention could supress inflammation and result in a reduction in allergy, but a dampened down immune system may be less able to fight infection. Pre-term infants are at particularly high risk of developing fatal necrotising enterocolitis and the incidence rate can be reduced considerably following specific probiotic administration. However, the mechanism may well be competitive exclusion and improved intestinal barrier function, rather than a direct effect of immune modulation. For these reasons, we are not yet in a position to promote interventions to rescue ‘at-risk’ infants who might be more susceptible to immunological-based diseases such as allergy and autoimmunity.
Avoiding antibiotics in early-life, caesarean births and formula feeding where possible is, in my opinion, the best option. Although clearly there are circumstances where these interventions are absolutely necessary. There is evidence that we are raising our children in very clean environments which is linked to increased immunological complications in later life. It is very important that we don’t expose children, especially young infants, to harmful microbes and should take all the necessary precautions when preparing and storing food and interacting with animals. However, we are perhaps a little over-cautious when it comes to getting them outside and a bit grubby.
7. What happens to our gut microbial composition as we age, and are there associations between these changes and our immune system?
The gut microbiota takes about 2-3 years to develop and then remains largely stable until old ages. I lecture on this subject and ask my student when they think old age starts. I usually get a rather depressing response of ‘at about 40‘. In reality, it’s probably much later than this. Although we are influenced by our microbiota, we also influence which types of bacteria are present and what they are doing, metabolically speaking. It’s a two-way interaction. Our immune systems deteriorate with age and therefore impact on our gut microbiota in different ways. There is evidence that the elderly often have reduced populations of a group of beneficial bacteria called Bifidobacteria. Enhancing the Bifidobacteria population can have beneficial effects on the immune system and help it to respond more appropriately when challenged. This could be by increasing the antibody response to vaccination, or by suppressing low-grade inflammation which often accompanies old age and can be detrimental to health. Although the results are promising at this stage, there is still a lot of work to be done in this area.
8. What do you like to do in your spare time?
I have two high energy dogs and two small, high energy children all of whom require a great deal of attention and have insatiable exercise requirements, which takes up most of my spare time. However, this year we have been rearing caterpillars which has been fascinating and the children have thoroughly engaged and taken their caterpillar responsibilities seriously. We have released Painted Ladies, Peacock and Tortoiseshell butterflies into the wild which has, albeit in a small way, boosted the local populations which are currently declining. We have witnessed these tiny, tiny creatures grow into huge caterpillars with voracious appetites. These appetites have resulted in me being out in our lane in my pyjamas collecting willow when they’ve caught me out and I’ve realised their current supply won’t last the night. Our favourite has been Stripy the colossal, bright yellow and blue death’s head hawk moth caterpillar who is currently dug down in a flowerpot of soil in our bathroom, slowly turning into a moth.
9. If you could give one tip to aspiring students, what would it be?
In terms of advice to students, mine would be to pursue a career in a subject which interests you and the financial reward shouldn’t be the primary reason for your choice. You’ll be working until you’re about a hundred the way things are going and it’s important for your life-long wellbeing that your work doesn’t become an unpleasant chore. We all have aspects of our jobs which we have to do whether we like it or not. But if the subject interests you, that’s half the battle won. Also, academic achievement is clearly important for many careers, but don’t underestimate the importance of transferable skills. Very few people are lucky enough to be born with the communication, organisational and group-working skills, for example, which are essential in most jobs. Instead, these can all be learnt and developed through practice. In my opinion, the best way to develop such skills is to make good use of the opportunities which come your way outside your academic studies. Join a committee, organise an event, take on a bit of additional responsibility. This will give you a head-start when it comes to your career.