SIMBA project update

I was recently asked to do a small newsletter for the SIMBA project shortly describing the intervention and where we were in the process of getting it started. I thought it would be a good idea to update you as well on the project process.

We have been working hard on getting the ethical approval and on the 16th of September we got the go-ahead. We have just hired Simon, a Ph.D. student, to help out with the practical work on the project. There will be a lot to do with recruitment, running examinations and other practical parts of running a human trial.

The newsletter also contains a short description of the major hypothesis and a bit about the design of the study. Hope you enjoy the news! (continues after the picture)

SIMBA project

SIMBA newsletter

Globally, the incidence of obesity and related metabolic diseases are steeply increasing, and this has major consequences both for individuals as well as the health care system worldwide. This urgently calls for early preventive strategies, but also for treatments targeting the early developing stages of diseases such as metabolic syndrome. The gastrointestinal system and the gut microbiome, in particular, have been proposed as a key target for such interventions. A dysbiotic, or altered, gut microbiome has been associated with increased metabolic and immune disorders in humans, affecting insulin secretion, fat accumulation, energy homeostasis and plasma cholesterol levels and initially manifests as metabolic syndrome, a health condition that places people at a higher risk of cardiovascular diseases, type 2 diabetes and some cancers. Therefore, the gut microbiome may serve as a potential therapeutic target for metabolic syndrome. However, only a few potential candidates for alleviating metabolic syndrome via gut microbiome manipulation have been tested in humans.

This is about to change with the SIMBA project. As part of Work Package 5, a novel, sustainable, fermented plant-based dietary supplement will be tested on humans. The product, developed by our partner FermBiotics, is a fermented canola-seaweed product that is produced via a lactic acid bacteria driven fermentation of canola (rapeseed) and seaweed. The product is rich in glycosinolates and putatively prebiotic oligosaccharides, and it’s projected to have a huge impact on the human gut microbiota, and thereby human health.

The intervention study will be carried out as a double-blinded, placebo-controlled randomized controlled trial using a parallel design, with 100 obese participants consuming 5 grams/day of fermented seaweed and canola, or a rye cereal placebo. The participants will be instructed to maintain their daily routines throughout the six-week study, and thus potential changes would be mediated only by the supplement.

We will study the effects of the fermented canola-seaweed product on glucose handling and related cardiometabolic traits such as dyslipidemia and low-grade systemic inflammation. At each visit, an oral glucose tolerance test will be conducted to investigate insulin sensitivity by measuring 30- and 120-min blood glucose. Moreover, a small number of participants will also be included in a sub-study where they will have blood glucose levels monitored with a 24-hour continuous glucose monitoring for 14 days. We will also measure anthropometry and blood pressure. Finally, we will examine the gut microbiota and the metabolic phenotype of the subjects to explore molecular mechanisms related to the potential improvements.

Recruitment of participants has started in October 2019 and the final participants are expected to finish the trial in March 2020. The study will provide a better understanding of how a sustainable, fermented plant-based dietary supplement could be used as a potential supplement to alleviate obesity-related metabolic disorders in a population at high risk of developing type 2 diabetes and cardiovascular disease. Furthermore, the study will examine whether the product can affect obesity-related metabolic disorders through modulation of the gut microbiota and host metabolome. We expect this study to enhance our insight into useful and valuable interventions for future development of microbiota-based interventions for patients with obesity and related metabolic disorders.

New Project – Sustainable European food systems using microorganisms – the SIMBA Project

SIMBA project

I’m happy to present another new project, SIMBA, not too long after introducing the Greenland Inuit dietary intervention study.

In a recent press release, the overall aim of the project was nicely presented. “SIMBA is a project funded by the European Union that will explore the potential of using microorganisms in plants and animals to improve food security and promote sustainable food production. This is to tackle the growing challenge of supplying food to a growing global population amidst the climate change crisis, through innovative activities around food systems using microorganisms.”

The research in this project is structured around studying microbiome applications in food systems to achieve sustainable innovative solutions for the growing demand for food and for agricultural production around the world. What I’m involved in is a minor part of the larger project. Here we are to test a product that lives up to the above description. Since this involves a company, I cannot reveal too much about the product yet, but this will involve conducting a human intervention study, which I look forward to beginning in Autumn 2019.

As the world population increases and the global climate is changing, we need to find suitable solutions for the supply of food so that it will not become a problem in the future. Worldwide, the demand for food and for agricultural produce is predicted to increase by up to 70% by 2050. Thus, there is an urgent need to improve and be innovative in our food production systems, which needs to meet this increasing demand for food. Here we hope that the SIMBA project will show the potential of microorganisms in this process.

You can follow the project on twitter @SIMBAproject_EU or follow my blog for specific updates on my little part of this huge project.

Gluten – The root of all evil?

So, you’ve probably heard about gluten – it has been linked to all kinds of diseases including autism, type 1 & 2 diabetes, and cancer. So what is gluten exactly and is it really the cause of so many diseases?

Wheat gluten gluten-free

Gluten is a much-discussed entity, which has been hyped for quite a while now. As mentioned above, it has been linked to of all sorts of diseases including autism, type 1 & 2 diabetes, various cancer types, osteoporosis, dementia & Alzheimer’s. Well, these postulations have been largely based on anything else than science – but there has been quite considerably advances in the research within this area in the past years which I will try to shed some light on taking my own research as an example.

But first, what is gluten? And celiac disease? These are important things to clear up since there seem to be some major misconceptions. Gluten is found in grains such as wheat, barley, and rye. Gluten is a mixture of proteins but the two major ones are gliadin and glutenin and these are responsible for some of the nice baking properties of bread made from these grains. Celiac disease is a condition in which gluten triggers immune system activity that damages the lining of the small intestine, which, over time, damages the intestine so much it prevents the absorption of nutrients from food.

No one seems to disagree upon the fact that people with celiac disease need to be following a gluten-free diet to avoid damages to the intestine and gastrointestinal symptoms. Not following a gluten-free diet for people with celiac disease has been linked to increased risk of cardiovascular diseases [1]. However, a more widespread belief is that everyone should be following a gluten-free diet despite not having celiac disease as this could have wide health benefits and thus following diets limiting gluten although being non-celiac gluten sensitive have gained huge popularity.

We recently published the results of a dietary study where we examined a low-gluten diet (2 grams/day) compared to a high-gluten diet (18 grams/day) in 60 overweight or obese adults without celiac disease over 8 weeks in a cross-over design (meaning they tried both diets in a random order)[2]. The hypothesis was that following a low-gluten diet compared to a high-gluten diet would change the gut microbiota/bacteria composition (which bacteria are present) and functional potential (how the bacteria work). We hypothesized that this would cause less subjective gastrointestinal discomfort, such as feeling bloated and would positively affect host metabolic and inflammatory markers[3]. In short, we tested the assumption that you would have a better gut feeling and become healthier by following a low-gluten diet and that this is caused by beneficial changes to your intestinal microbiota. We provided the participants with matched grain products, which were either gluten-free or containing gluten. For example, in one period, they got ciabatta wheat bread (high in gluten) and in the other period, they got a gluten-free bread (buckwheat, sunflower seeds etc.). We did thorough examinations of the participants in the beginning and end of each period. This sounds relatively simple when I write it, but in total, these examinations took over 1.5 years to complete and involved multiple people (including the 52 authors on the paper), so a substantial amount of time and effort went into this.

What did the dietary change do then? We found that people actually felt less bloated on a low-gluten diet compared to a high-gluten diet. This change was probably related to changes in the fermentation and gas production of the intestinal microbiota, which we found was lowered after being on the low-gluten diet. The participants also reported a higher well-being after a standard breakfast meal. We did find a minor weight loss of about 800 grams when following a low-gluten diet (Hardly anything you could sell in a magazine stating “Loose 800 grams in 8 weeks”) and some selective changes in the inflammatory markers, which were quite hard to interpret.

So was this caused by gluten? Well, changing the grain types to gluten-free also changed major parts of the dietary fiber types. The difference in fiber types, as well as the absence of gluten itself, might explain the changes in subjective gastrointestinal feeling. One of the reasons we think that the dietary fiber change is the cause of the changes in gastrointestinal feeling was that we found changes in the gut microbiome composition and functionality which seems to be related to the carbohydrate/fiber metabolism of the gut bacteria. Another reason is that an earlier study has shown that when giving gluten to people with self-reported non-celiac gluten sensitivity on top of a low FODMAP diet (a diet low in fermentable carbohydrates) no gastrointestinal effects were shown[4]. They showed that it was when changing to a low FODMAP diet that their gastrointestinal symptoms were lowered. So, my interpretation is that some people are sensitive to certain fiber/fermentable carbohydrates causing gastrointestinal discomfort and that this is not related to gluten. But who these people are and why they are sensitive to fiber/fermentable carbohydrates is less clear – at least to me.

Should you begin following a gluten-free diet, if you don’t have celiac disease? More and more research seems to be showing that there might be some downsides to choosing a gluten-free diet. One example of this is that higher gluten intake has been associated with lower risk of type 2 diabetes[5]. Others have shown that Americans reporting that they follow a gluten-free diet were exposed to higher levels of arsenic and mercury[6]. Some have shown that gluten intake is not associated with risk of coronary heart disease, but following a gluten-free diet may result in avoidance of whole grain, which lowers the risk of coronary heart disease[7].

Therefore, in my opinion, gluten is not your enemy or the root of all evil. It might just have been mixed in with fiber/fermentable carbohydrates that cause gastrointestinal discomfort in some people. And this should not keep you from getting some very valuable whole grains.

But this blog post is probably not going to end the discussion on gluten and nor should it. As always, more research is probably needed as some people might actually benefit and improve their quality of life substantially by altering their diet. Also special diets, following principles like FODMAPs, is an important research area as it might be useful for patients with chronic gastrointestinal disorders such as ulcerative colitis and Crohn’s Disease (Link). Furthermore, gluten-free diets are important for people with celiac disease, and having products with high nutritional value for this group of people is important.

Disclosure
As I have already written in my about page I have a possible conflict of interest as I was partly supported by an unrestricted grant from Cereal Partners Worldwide; a joint venture between Nestlé SA and General Mills Ltd which manufactures and sells grain products. They covered the last 1/3 of my PhD funding which was actually the reason for me being able to do a PhD. They played no role in the design, methods, data management, and analysis nor in the decision to publish in any of the studies.

References

[1] Ludvigsson JF, James S, Askling J, et al. Nationwide Cohort Study of Risk of Ischemic Heart Disease in Patients With Celiac Disease. Circulation 2011;123:483–90. doi:10.1161/CIRCULATIONAHA.110.965624.

[2] Hansen LBS, Roager HM, Søndertoft NB, et al. A low-gluten diet induces changes in the intestinal microbiome of healthy Danish adults. Nat Commun 2018;9:4630. doi:10.1038/s41467-018-07019-x.

[3] Ibrügger S, Gøbel RJ, Vestergaard H, et al. Two Randomized Cross-Over Trials Assessing the Impact of Dietary Gluten or Wholegrain on the Gut Microbiome and Host Metabolic Health. J Clin Trials 2014;4. doi:10.4172/2167-0870.1000178.

[4] Biesiekierski JR, Peters SL, Newnham ED, et al. No Effects of Gluten in Patients With Self-Reported Non-Celiac Gluten Sensitivity After Dietary Reduction of Fermentable, Poorly Absorbed, Short-Chain Carbohydrates. Gastroenterology 2013;145:320–328.e3. doi:10.1053/j.gastro.2013.04.051.

[5] Zong G, Lebwohl B, Hu FB, et al. Gluten intake and risk of type 2 diabetes in three large prospective cohort studies of US men and women. Diabetologia 2018;61:2164–73. doi:10.1007/s00125-018-4697-9.

[6] Bulka CM, Davis MA, Karagas MR, et al. The Unintended Consequences of a Gluten-free Diet. Epidemiology 2017;28:e24–5. doi:10.1097/EDE.0000000000000640.

[7] Lebwohl B, Cao Y, Zong G, et al. Long term gluten consumption in adults without celiac disease and risk of coronary heart disease: prospective cohort study. BMJ 2017;357:j1892. doi:10.1136/bmj.j1892.