Early gut health and lifelong impact: Inside the CALINA-IBD study

Canada has one of the highest rates of inflammatory bowel disease (IBD) in the world, with approximately one in 140 Canadians currently diagnosed — a number expected to climb to one in 100 by 2030. 

In this episode, registered dietitian and PhD student Mathilde Wilhelmy joins us to discuss CALINA-IBD, a new study from Dr. Genelle Lunken's Lab at BC Children's Hospital Research Institute and UBC. The study is exploring how the maternal gut microbiome and diet during pregnancy, along with breastmilk composition, may shape infant gut inflammation and long-term health.

The conversation unpacks what fecal calprotectin (FCP) is, why infants naturally have higher levels than adults, and how elevated infant FCP has been linked to later risks of asthma, eczema, and atopic dermatitis. Mathilde also discusses why the team is paying attention to certain anti-inflammatory bacteria, well-established benefits of a Mediterranean-style diet for gut microbiome diversity, and what human milk oligosaccharides (HMOs) — the special sugars found almost exclusively in breastmilk — might reveal about how to better support at-risk infants. She walks through the four-timepoint study design, the at-home participant experience, and a machine learning collaboration with Dr. Amy Lee at SFU that aims to one day help clinicians identify higher-risk infants earlier and guide more personalized care.

Learn more about the topics discussed in this episode:

CALINA-IBD study, Lunken Lab, BC Children's Hospital Research Institute

Exploring the gut microbiota and dietary contributors to elevated infant fecal calprotectin in patients with inflammatory bowel disease: A pilot study (CALINA-IBD), ClinicalTrials.gov

Interested in participating? Click here to take the screening questionnaire.

Please note: The CALINA-IBD study also collects breast milk samples and breast skin swabs at two postpartum timepoints (two weeks and three months). This portion of the study is optional.

Participants who choose to take part will be provided with all necessary collection materials. A breast pump can also be provided if they do not already have one at home.

For more information, please contact the study team at calina.ibd@ubc.ca.

All episodes written and produced by the Research Communications team at BC Children's Hospital Research Institute.

Theme music: "Life Is Beautiful" by Anastasia Kir

Transcript

Kristen Hovet 0:00

Canada has one of the highest rates of inflammatory bowel disease in the world, and many people are diagnosed during their reproductive years. I'm Kristen Hovet, and I'm the Interim Research Communications Manager for BC Children's Hospital Research Institute. Joining me today is Mathilde Wilhelmy, a registered dietitian and PhD student in the Women's and Children's Health Program at UBC and a member of Dr. Genelle Lunken's lab at BCCHR. We'll be talking about the CALINA IBD study, exploring how the gut, microbiome, and diet during pregnancy, along with breast milk composition, may shape infant gut inflammation and why the earliest months of life could be such a critical window for supporting lifelong health.

Mathilde Wilhelmy 0:44

My name is Mathilde. I'm a registered dietitian in the province of Quebec. I completed my undergraduate studies in dietetics at McGill University. And then after graduating, I worked as a dietitian in Montreal for almost a year. And then that's when I realized how prevalent gut-related issues were in our population. And I got really more into gut health and the gut microbiome, which is the community of microorganisms like bacteria, viruses, fungi, and archaea that live in our gut. And I wanted to study this more. And so I reached out to Dr. Genelle Lunken at UBC to see if she had any opportunities for me to do a master's. And so I started my master in 2024, so two years ago, in the Women's and Children's Health program at UBC. I got really into the project that we'll talk about today. And now I'm currently transitioning to a PhD with the same project. And my research focuses broadly on maternal health, the gut microbiome, and how maternal factors during pregnancy may influence both maternal outcomes and early infant health, which is what we're discussing today.

Kristen Hovet 1:54

Awesome. Thank you. For listeners who may be hearing about inflammatory bowel disease or IBD for the first time, could you walk us through what IBD is and why pregnancy is such an important window to study in this population?

Mathilde Wilhelmy 2:08

Yeah, so inflammatory bowel disease, or in short, IBD, is a chronic condition involving ongoing inflammation of the gastrointestinal tract caused by an inappropriate immune response to gut microbes and genetic predisposition. So there are two main types of IBD. So there's Crohn's disease and ulcerative colitis. And the symptoms of this disease include abdominal pain, diarrhea, fatigue, rectal bleeding, and sometimes even weight loss, although symptoms and severity can vary greatly from person to person. But for many individuals, IBD requires lifelong management with medications and sometimes even requires surgery. And the exact causes of IBD are not fully understood, but researchers believe that disease develops through a combination of genetic predisposition and environmental factors, and potential triggers could include smoking, a Western dietary pattern, which is a diet that is more rich in fat and sugar, as well as stress, certain medications, could also be pollution, and other lifestyle-related factors. And increasing evidence also suggests that the gut microbiome, which is what I talked a little earlier, which is a complex ecosystem of trillions of microorganisms that live in our gut, may also have an important role to play in IBD. However, it's still unclear whether changes in the microbiome contributes to the development of inflammation or whether inflammation itself alters the gut microbiome. And then in terms of prevalence, Canada has one of the highest rates of IBD in the world. And currently there's about one in 140 Canadians that are diagnosed with IBD. And this number is expected to continue increasing, unfortunately, with about one in 100 Canadians by 2030. So IBD represents a very growing public health concern in Canada, with healthcare costs exceeding around $5 billion annually. Why is it important to study it for pregnancy? So IBD can develop at any age, but it is most diagnosed during adolescence and early adulthood, often during peak reproductive years, so between the ages of 15 to 30. And this makes pregnancy and reproductive health very important for research for this population. But pregnancy is also a unique period involving major changes such as hormonal, immune, metabolic, and microbial changes. And then what studies have found is that individuals with IBD, these changes may influence the disease activity. And while active inflammation, so when the disease is active during pregnancy, it may be associated with increased risk of complications for pregnancies, such as preterm birth, low birth weight, and small for gestational age. And so research has shown that maintaining a disease in what we call remission, so as low inflammation as possible before and during pregnancy, is one of the most important predictors of healthy pregnancy outcomes in this population. And so what we want to do is to understand a little bit more of the gap in this field. So historically, pregnant individuals have often been underrepresented in clinical research. And when we add on IBD research, there's very limited research on this topic. And so what we want to do is to fill in some of the gaps in the literature. I think it's very important to study pregnancy in the context of IBD.

Kristen Hovet 5:30

So you already kind of answered this, but what specifically led to the CALINA IBD study taking shape?

Mathilde Wilhelmy 5:37

Yes. So one of our collaborators for the study is the IBD Centre of BC. And we are collaborating with different gastroenterologists that work with this population specifically. And they have a pregnancy clinic, and so they see lots of pregnant women. And they did a study, which is Dr. Yvette Leung, who was leading the study, and they looked at pregnancy outcomes for this population. And if there's an increased risk of certain complications during pregnancy when someone has IBD, and what they observe is what I mentioned earlier, when the disease is in remission, so when there's very limited inflammation, then the pregnancy outcomes are very similar to those of the general population. However, when the disease is active, so before conception, so before getting pregnant or during pregnancy, that might increase the risk of pregnancy complications. And they observed that for certain people, they would get an increased disease activity during pregnancy, especially in the second trimester, and that causes some complications. So we want to make sure that the disease stays as low inflammation as possible. But then how do we do that? So this is why we decided to do this study, and we wanted to look at specifically some modifiable factors, such as diet and the gut microbiome, and seeing if we can modify those things and then optimize the disease, having lower disease activity during pregnancy and then having lower inflammation and then potentially having better pregnancy outcomes and infant outcomes as well.

Kristen Hovet 7:08

Thank you. One of the key markers your study will look at is something called fecal calprotectin. I hope I'm saying that right, or FCP. Can you explain what FCP is, what it tells us about an infant's gut, and why elevated levels in babies born to parents with IBD are something researchers want to better understand?

Mathilde Wilhelmy 7:30

Yeah. So fecal cal protectin or FCP is a protein released by certain immune cells called neutrophils during pregnancy, produced in the gut, and we can measure them in stool samples. And it is already widely used in clinical care as a marker of intestinal inflammation, particularly in conditions such as IBD. So in adults with IBD, elevated fecal calprotectin levels are often used to help determine whether there's an active inflammation occurring in the intestine, and it can help clinician monitor disease activity, assess response to treatment, and sometimes even predict disease flares without needing to do some invasive procedures like colonoscopies. So this is great. But then when it comes to infant, so in infants, it's a little bit more hard to interpret because it's more complex. So unlike adults, infants naturally have higher fecal calprotectin levels because their immune system, intestinal barrier, and gut microbiome are all still developing. So during infancy, the gut is essentially learning how to distinguish between harmless microbes, food particles, and what can be potential threats. So because of this rapid immune and microbial development inflammation marker that would be considered abnormal in adults may be normal in infants. The challenge is that we still do not fully understand what constitutes a normal versus potentially concerning fecal calprotectin levels during infancy across different populations and health conditions. So this is one of the main reasons why we wanted to study this in our study. And there's one study that got published in 2021 that was very interesting that looked at fecal calprotectin levels in infants born from IBD mothers, and they observed that those babies had higher fecal calprotectin levels compared to the babies born from parents that did not have the disease. And so that just got us very interested in this. And so this is why we want to look at it. But it's not necessarily because your infant has a high fecal calprotectin levels that it means that the baby will have the disease necessarily.

Kristen Hovet 9:36

Interesting. And I know existing research has linked higher infant FCP levels to later risk of asthma, eczema, and IBD itself. How do you and your team think about that early life window, pregnancy through the first year, as an opportunity for prevention?

Mathilde Wilhelmy 9:53

There's an increasing thinking about pregnancy in the first year of life, very important as like the window of opportunity for long-term health and prevention. So during this period, the infant immune system, gut microbiome, and intestinal barriers are all rapidly developing and learning how to interact with the environment. Research is showing that early life gut inflammation influences the risk of immune-mediated conditions later in childhood, including asthma, eczema, could also be allergies, even potentially IBD later in life. And there's one study that found that infants with very high fecal calprotectin levels at two months of age had higher risk of developing atopic dermatitis and asthma at age six. So the study suggested that early microbial exposure may train the immune system. So certain bacteria appear to stimulate anti-inflammatory immune pathways. And so certain bacteria might help the microbiome and then regulate inflammation. But then in this early immune education, when this is altered by some more pro-inflammatory bacteria, it may contribute to more inflammatory immune profile later in life. And this is why maybe sometimes the infants will have higher fecal calprotectin levels and then potentially having more allergies or more eczema or atopic dermatitis. However, I just wanted to note that our team sees this research as an opportunity to move towards early prevention rather than waiting until disease develops later in life. But we are still far from saying that fecal calprotectin levels directly cause these conditions or can predict disease on its own. But it may be helpful for us to better understand which early life patterns are associated with healthier or less healthy immune development.

Kristen Hovet 11:42

I know your study will pay particular attention to a couple of specific bacteria and to whether the birthing parent is following a Mediterranean-style diet. Why are those bacteria and that dietary pattern key aspects of the study?

Mathilde Wilhelmy 11:58

Yeah, so those are key aspects of the study because both the Mediterranean style diet and certain gut bacteria, particularly faecali bacterium and bifidobacterium, have been consistently associated with gut immune health. So when we start with fecal bacterium, this group of bacteria is often considered one of the beneficial anti-inflammatory bacteria in the gut, and it produces compounds that we call short-chain fatty acids that produce butyrate, which helps nourish the cell lining and the intestine and strengthen the intestinal barrier and regulate inflammation. So lower levels of these bacteria have frequently been observed in individuals with IBD and in other inflammatory conditions. So we want to have these bacteria as much as possible. Same thing with bifidobacterium. So this is another important group of bacteria that is strongly associated with gut health and immune regulation. So these bacteria are involved in maintaining gut barrier integrity, supporting immune balance, and helping metabolize certain dietary fibres and compounds. And so again, having higher levels of these bacteria are generally associated with a healthier and more diverse gut microbiome, while reduced levels of these bacteria are linked to inflammation and a more disruption or imbalanced gut microbiome, especially in people living with IBD. So when we talk about the Mediterranean diet, so this is very relevant because it's one of the only dietary patterns that is consistently associated with lower inflammation and greater gut microbiome diversity. So it typically emphasizes foods like fruits, vegetables, legumes, whole grains, nuts, olive oil, fish, and some healthy fats, as well as higher fibre foods. So this interest in diet and IBD has been supported by larger studies such as the GEM project, which has followed healthy first-degree relatives of individuals with Crohn's disease to better understand environment and microbial factors involved in disease development. And what they found in the study is that people that were, had a lower adherence to this Mediterranean diet were associated with a microbiome pattern that was linked more to increased risk of Crohn's disease and more imbalanced microbiome. Whereas people that were following this diet or had a higher Mediterranean diet style of eating, they had a more diverse microbiome and a little less inflammation markers. So these foods help beneficial gut bacteria and promote the production of anti-inflammatory compounds such as short chain fatty acids that I mentioned before. But in contrast, foods that are more ultra-processed foods, such as saturated fats or added sugars, are often referred as what we call the Western diet, which is a diet more rich in fats and sugars and have been associated with a more reduced microbial diversity and more pro-inflammatory microbial profiles. So in our study, we really want to look at if the Mediterranean diet has an impact on the microbiome and especially on the microbiome of people living with IBD.

Kristen Hovet 15:04

Your team will also be looking at the sugars in human breast milk and how they may differ between birthing parents with and without IBD. What's already known about how these sugars shape an infant's gut bacteria? And what are you hoping CALINA IBD will add to that picture?

Mathilde Wilhelmy 15:22

Breastfeeding is considered the ideal source of nutrition for newborns, as recommended by the World Health Organization. So we've known for a long time that early feeding plays a key role in shaping the infant gut microbiome. In fact, breast milk in infants tend to have a microbiome enriched in beneficial bacteria, such as bifidobacterium and lactobicillus, compared to formula fit infants. And so breast milk itself is incredibly complex and dynamic. It contains antibodies, proteins, fats, carbohydrates, and even some micronutrients that are all important for the infant development. So one of the most interesting components for our study precisely is human milk oligosaccharides, or in short, HMOs. These are special sugars found almost exclusively in breast milk, and babies can't digest them directly, but they act as a powerful prebiotics, meaning that they selectively feed the beneficial gut bacteria in the gut, and then they help the bacteria to grow in many different ways, and it produces what we call short chain fatty acids that help strengthen the gut lining, reduce inflammation, and support immune system development for the babies. When it comes to IBD, we know that breast milk composition can differ. So earlier studies showed differences mainly in immune-related components like antibodies and inflammation marker. More recently, a study called the MECONIUM Study found differences in breast milk protein composition, but they didn't really look at HMO directly. So this is why in our study, as we're looking at the gut microbiome of the baby, we really want to look at HMO profiles as they can feed the good bacterias and see if breast milk that is higher in HMOs can potentially have a beneficial impact on the gut microbiome of the infant, as well as to compare IBD mothers versus non-IBD mothers and if they have differences in HMO profiles in their breast milk.

Kristen Hovet 17:25

That's so cool, and the study is designed to be completed 100% from home. Can you walk us through what's involved for participants?

Mathilde Wilhelmy 19:56

Yes, participation in CALINA IBD is designed to be as low burden as possible and entirely at home, as you mentioned. And it's especially important, I think, when we talk about pregnancy and also we are looking at afterbirth. So when the parent has a newborn. Once someone's enrolled in the study, all participation happens remotely. And this includes completing online surveys. These questionnaires cover topics such as diets, symptoms, medication, lifestyle factors, and infant feeding and development after birth. And there's four main time points in our study. So there's one the third trimester, so around week 35 of gestation, one two weeks postpartum, one three months postpartum, and one one year postpartum. So what we're asking participants to do, the first time point, we're asking them to collect diet information. And so we're using an app called RX Food. So participant will receive how to access the app. And then the app is really great because they only have to take photos of their meals and snacks. So they don't have to write down all of the quantities of what they're eating and exactly what they're eating. So the app is an AI, a recognition app that can recognize how much and what is on your plate, which is great, especially when you're on the way to have a baby and then after birth as well. So then we're asking them to take photos of their meals and snack for three days. And then after those three days, we're collecting stool samples from the mother as well as a vaginal swab to look at the vaginal microbiome as well. So that's for the third trimester. And then we have time points after birth. So two weeks, three months, and one year, and we're asking the same thing at those three time points. So what we're asking them is to again collect three days of food diary. So taking photos of their meals using the same app for three days, and then after that to collect their own stool sample and their baby's stool sample. So now we're looking at their own microbiome, but also the baby's microbiome. So that's for two weeks, three months, and one year postpartum. Yeah, and I think the study is great because what you get after this study is you get your microbiome results. You also get your fecal calprotectin levels of yourself and your baby. We are also giving out the reports from the diet app. So you get all the macro and micronutrients, and then you can see if maybe you're eating a little less of some of the essential micro or macronutrients.

Kristen Hovet 22:19

Very cool. And those samples, you said the stool samples, that's all remote as well? They're sending those in?

Mathilde Wilhelmy 22:26

Yeah, exactly. It's all collected at home, and then you post them after. Yeah.

Kristen Hovet 22:30

What can listeners do if they'd like to get involved?

Mathilde Wilhelmy 22:33

Yeah, so they can look at our website. And on our website, we have a screening questionnaire. So they can answer that. It's four questions, I think, very quick, and then we will contact them directly after.

Kristen Hovet 22:45

A question we ask all podcast guests: how does your research help children live their best lives?

Mathilde Wilhelmy 22:52

Yeah, so the idea behind our study is that the earliest stages of life, starting in pregnancy and continuing throughout infancy, represents a critical window for shaping both the immune system and also the gut microbiome. So these early exposures can have lasting effects on the child's growth, digestion, immune function, and potentially even long-term health or long-term risk of disease. So what we're trying to do is to better understand modifiable factors during this period, such as diet. And then by identifying those factors that interact, we can hope to understand how to support healthier pregnancy and infants environment and ultimately healthier beginnings for infants. So in the long term, this kind of research can help move us towards more personalized guidance, such as nutrition recommendations that directly target the gut microbiome and earlier intervention to support both maternal health and give children the best possible start in life.