Science for Society

What should we know about celiac disease?

International Celiac Disease Day is celebrated on May 16 in all countries belonging to the AOECS. Established in 2006, it draws attention to gluten-dependent diseases and the challenges faced by consumers following a gluten-free diet, but also by food producers, for whom the market has growing expectations. Dr. Urszula Krupa-Kozak from the Department of Chemistry and Biodynamics of Food, talks about celiac disease and the relevant research being conducted at our Institute.

Many people who consume grain products report distressing symptoms, worsening health and reduced quality of life. Gluten, which is a complex of wheat reserve proteins (gliadin and glutein) and the homologous proteins of rye (secalin) and barley (hordein), can cause the development of gluten-dependent diseases, which include celiac disease, Dühring syndrome, gluten ataxia, wheat allergy and non-celiac gluten hypersensitivity. Celiac disease (a.k.a. visceral disease, gluten-dependent enteropathy) is an autoimmune disease that occurs in genetically predisposed individuals, caused by persistent gluten intolerance. The disease is characterized by a varied clinical picture, the presence of specific serum antibodies and haplotype (group of genes inherited from one parent – ed.) HLADQ2 or HLA-DQ8, and enteropathy (pathological changes – ed.) in the small intestine. The disease leads to damage to the intestinal mucosa, followed by atrophy of the intestinal villi, whose function is to absorb nutrients.

Diagnosis

Gluten-dependent diseases can manifest themselves with different symptoms, which can additionally vary in severity. Classic celiac disease (full-blown) is characterized by symptoms of malnutrition, abdominal pain, weight loss; it is accompanied by diarrhea, bloating, and in children, personality changes and developmental disorders. This form of the disease is relatively rare, and is diagnosed relatively quickly due to its characteristic symptoms. Much more often, however, patients with celiac disease have extraintestinal symptoms (anemia, chronic fatigue, aphthas, neurological disorders, bone and joint pain, premature osteoporosis, fertility problem), which should draw the attention not only of gastroenterologists, but also of endocrinologists, gynecologists, hematologists, rheumatologists or neurologists. Non-celiac gluten hypersensitivity (NCGS) is characterized by symptoms similar to celiac disease and irritable bowel syndrome, with which it can be confused. The condition mainly affects adults and is characterized by symptoms beyond the gastrointestinal tract.

People who observe alarming symptoms in themselves after consuming gluten-containing products and suspect the development of gluten-related diseases should consult their GP. The doctor, based on the medical history, will order a consultation with a specialist – a gastroenterologist in a justified case. The specialist in the next step will order the determination of celiac disease-specific antibodies (tTG and EmA), the presence of which in the blood serum indicates the disease, but does not always mean changes in the small intestine, authorizing its diagnosis. Therefore, for a complete diagnosis of celiac disease, biopsy and histopathological evaluation of small intestine sections, which are the gold standard for diagnosis in adults, are necessary. In the case of NCGS, diagnosis relies on the exclusion of other gluten-dependent diseases (celiac disease and wheat allergy), as there are no specific markers to detect this type of hypersensitivity.

What’s next?

For gluten-dependent diseases, the basic and common form of therapy is to exclude gluten from the diet. The differences, however, are that in the case of celiac disease, a gluten-free diet must already be followed rigorously and for life, while in the case of allergies and NCGS, the diet can be followed temporarily.

A gluten-free diet involves eliminating foods made from grains, i.e. wheat (including spelt, flatbread, semolina), barley, rye and uncertified oats. Commercially, gluten-free products are marked with a crossed ear sign. However, unlabeled products can be a problem, especially those in which gluten is not expected such as cured meats, sauces, spice blends, dressings, yogurts or gum, and even some medicines that may have been contaminated with this protein in the manufacturing process.

In the initial stages of treatment, right after diagnosis, the support of a qualified nutritionist is very important and helpful in properly balancing a gluten-free diet. However, once you become familiar and „accustomed” to its principles, following the diet in your own home becomes a habit. Meals away from home, in restaurants, at school/preschool or while traveling can be a problem. That’s why it’s a good idea to ensure your safety by planning your meals well, choosing only reliable restaurants and catering companies. Although products with the crossed-thorn mark are now available for purchase, it is advisable to prepare a set of tried-and-true gluten-free products for trips, consisting, for example, of bread, cookies, nuts and fruit. It’s also a good idea to be mindful of your diet when traveling by air and to book a gluten-free meal in advance.

Trendy „gluten-free”

Without consulting a gastroenterologist and without a definitive diagnosis, you should not switch to a gluten-free diet on your own. This will make it more difficult and prolong the time for a proper diagnosis because when we eliminate gluten from the diet, the body will not be in contact with this factor and will stop producing characteristic antibodies, so that the results of serological tests will be inaccurate or falsely negative.

Flaxseed cake as an opportunity to improve gluten-free products

Recent research conducted by scientists at the Institute of Animal Reproduction and Food Research, in cooperation with the West Pomeranian University of Technology, has focused on improving the quality and enrichment of gluten-free baked goods with nutrients and bioactive ingredients derived from flaxseed cake, the pomace from linseed oil production. Compared to conventional bread, a common disadvantage of commercially available gluten-free baked goods is poor quality due to inferior taste, unsatisfactory texture and reduced nutritional value and short shelf life. The need to improve the quality of baked goods led researchers to study the nutritional and functional potential of flaxseed cake, which has been shown to be a good source of minerals and antioxidants. In addition, along with flaxseed cake, proteins and polysaccharides are introduced into bread recipes, which have a beneficial effect on the technological properties of bread, giving it the desired cohesiveness, porosity, colour and even aroma. The research conducted by the teams from Olsztyn and Szczecin is important from the point of view of consumers on a gluten-free diet, who have the right to expect that the quality of gluten-free products available commercially will be similar to conventional products. In reality, however, this is not easy to achieve and poses a great challenge for food technologists and producers.

Adenomyosis – learn about a female disease similar to endometriosis

Until recently, it was believed that if a woman had a problem with heavy menstrual bleeding, fertility or menstrual pain, then „this is her beauty”. Today we know that these may be symptoms of, for example, adenomyosis – a female disease similar to endometriosis. The research results of scientists from the Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences in Olsztyn may improve the diagnosis and treatment of this condition.

The publication on this topic appeared in the journal „Journal of Clinical Medicine” .

ADENOMMYOSIS – A LESS KNOWN FORM OF ENDOMETRIOSIS

Adenomyosis is an estrogen-dependent disease similar to endometriosis. In endometriosis, endometrial tissue, the lining inside the uterus, abnormally migrates to other places in the body, including the intestines or around the anus. With adenomyosis, these tissues get into in the uterine muscle – explains the author of the study, Maria Sztachelska, MD, PhD from the Department of Biology and Pathology of Human Reproduction IRZiBŻ PAS in Olsztyn.

The main symptoms of adenomyosis are very heavy menstrual bleeding, perimenstrual pain and pain during intercourse, thickening of the uterine walls in the ultrasound image, infertility problems, general malaise, and a tendency to anemia.

The exact mechanism of adenomyosis formation is not yet known. As Maria Sztachelska emphasizes, one of the theories is the presence of excessive contractile activity of the uterus, which leads to micro-trauma and the mucous membrane tissue inside the uterus instead of exfoliating outside (during menstruation) penetrates inside this wall.

(NOT) ESSENTIAL ESTROGEN

Adenomyosis is an estrogen-dependent disease, which means that estrogens are the key hormones driving its growth.

“In our studies, we wanted to determine the profile of hormone receptors and we showed the presence of all nuclear and membrane estrogen and progesterone receptors. We suspect that in the case of adenomyosis – as in endometriosis – the mechanism of disease formation is most likely related to the expression of the beta estrogen receptor, which is not present in the normal endometrium – the researcher points out.

Studies have also shown that adenomyosis is able to drive its own development, because its tissues themselves produce estradiol (biologically active estrogen), and this promotes cell proliferation. – In addition, adenomyosis also produces prolactin, which inhibits apoptosis, i.e. the process of cell destruction. All this increases the lifespan of adonemiosis and therefore its complete recovery is still a challenge – emphasizes Maria Sztachelska.

BETTER DIAGNOSIS AND TARGETED THERAPY

Currently, adenomyosis can be treated in two ways. The first path is radical, surgical treatment.

– The second option, often used after the procedure, is pharmacological treatment. Currently, the therapy most often consists in the use of GnRH antagonists, which inhibit the production of estradiol. However, they cannot be used indefinitely, because estradiol is necessary for a woman – it affects e.g. skin, hair, nails, well-being. Our previous research, led by Dr. Donata Ponikwicka-Tyszko, on the biology of endometriosis, indicates that GnRH antagonist therapy in combination with estradiol can be used long-term and has good effects. Currently, the potential of targeted therapy, e.g. in the form of antibodies directed at specific receptors, is also being investigated, emphasizes Maria Sztachelska.

The test results may also contribute to better diagnosis. „Since we showed a high expression of the estrogen receptor beta, knowing this altered profile of receptors, it would be possible to determine whether a woman is potentially at risk of adenomyosis by examining the endometrial tissue taken in a biopsy, even before the onset of symptoms” – the researcher points out.

– Until recently, it was believed that if a woman has a problem with heavy menstrual bleeding, fertility or menstrual pain, then „this is her beauty”. Fortunately, today the awareness and detection of endometriosis or adenomyosis is increasing. And this is not a marginal problem, because these diseases can affect up to every fifth woman – sums up Maria Sztachelska.

A step towards a 'vaccine’ for egg allergy

Lymphocytes are white blood cells that regulate the immune system. If they have some „experience”, e.g. with an allergenic protein and get transplanted into another organism, then such a transfer will strengthen the immune reaction and the body will start to defend itself better against this protein.

Such an experiment was conducted by scientists from our Institute. They showed that transplanted CD4+ T cells that were in contact with hen’s egg white enhanced the immune response to it. The results were published in the International Journal of Molecular Science.

– The results of our research may be a step towards developing methods of treating patients with allergies – emphasizes the author of the research, Dr. Dagmara Złotkowska from the Department of Immunology and Food Microbiology IAR&FR PAS in Olsztyn.

HOW ALLERGIES HAPPEN

A food allergy is an abnormal reaction of the body’s immune system to a specific compound, which is an allergen. So it is a type of food hypersensitivity that causes unwanted food reactions, involving the immune system.

In the fight against food allergies, T lymphocytes, i.e. white blood cells, play an important role in regulating the immune system response. – This is a group of cells specializing in defending our body against the undesirable effects of potential allergens – explains Dr. Dagmara Złotkowska.

If we „teached” cells how to recognize and neutralize specific allergenic proteins, these „teachers” could be transferred (e.g. in the form of vaccines) to the body of allergy sufferers to minimize its immune response. – This can be compared to the mechanism of the mRNA vaccine against COVID-19, where – to put it simply – we do not provide the cells with a virus, but with a „set of instructions” on how to produce antibodies – the researcher points out.

EXPERIMENTAL TRANSFER

The team from the Department of Immunology and Food Microbiology of IAR&FR PAS in Olsztyn focused on allergy to hen’s egg protein and the possibility of cross-reactivity with chicken meat proteins. This meat is a common component of the modern diet; allergy to them is relatively rare and occurs independently or in people allergic to egg white (OVA, or ovalbumin, is the main protein found in egg white). CD4+ T cells, on the other hand, are special immune cells that recognize allergens, including the OVA protein.

The experiment involved transplanting experienced (those that had already been in contact with OVA) CD4+ T cells into the body of an animal that was allergic to OVA and fed chicken meat. – It turned out that such a transfer helped to improve the negative immune response to OVA, that is, it strengthened the body’s immune response to the OVA protein, which was previously not recognized and fought off by the immune system. To put it simple, the body began to defend itself better against this protein – indicates Dr. Dagmara Złotkowska.

A CURE FOR FOOD ALLERGY?

The approach of the researchers from Olsztyn is innovative and may contribute to the development of treatment methods for patients with allergies. – So far, the most effective way to treat food allergy is to exercise the elimination diet – which eliminates not only allergens, but also other cross-reacting proteins. I doubt whether we will find a „cure” for allergy in the near future, because many factors and mechanisms affecting it are still not known. The results of our research may, however, be a step towards developing methods of treating patients with allergies, e.g. by giving them „trained” groups of cells that could reduce the immune response to a given allergen. There are still many years of research ahead of us, but the direction seems promising – the researcher concludes.

Dr. Magdalena Weidner-Glunde and PhD student Mamata Savanagouder featured as experts in the documentary series „Virus Hunting”

„They are mistakenly seen as a companion only to the cold months (…) Some cause harmless infections, others are a deadly threat,” these words begin the documentary series „Virus Hunting”, which takes a closer look at the achievements of scientists working on the front lines of the fight against viral diseases. The first episode of the series featured Dr. Magdalena Weidner-Glunde, head of the Laboratory of Molecular Microbiology and Virology at our Institute, and Mamata Savanagouder, a PhD student in her team.

Dr. Weidner-Glunde explains what the virus is and why cytomegalovirus research is being conducted at the Institute.

The virus is the kind of package that is supposed to reach the cell and allow the virus to multiply there. This package on the outside has a protein envelope, the so-called capsid, which protects the genome inside. Once inside the cell, this genome is released and allows the virus to replicate, multiply and create new viral particles. – Dr. Weidner-Glunde explains in the episode.

Cytomegalovirus in most cases in healthy people does not cause major problems or strong symptoms, possibly mild cold symptoms. It becomes a problem if the infection occurs in a pregnant woman, because the most common result is partial or total hearing loss in the fetus, later in the newborn. In addition, the problem is that in many cases children are born healthy and only lose their hearing after some time. – she adds.

We encourage you to watch the first episode of the series „Virus Hunting”.

Spring is coming, so turn your face to the sun and grab some vitamin D

After the autumn-winter period, our body needs vitamin D. Scientists have proven that even a balanced and varied diet is not enough to provide the total daily dose of this vitamin, because skin synthesis is its main source for the body. That’s why they advise you to expose your face to the sun in the spring and catch some vitamin D.

The latest recommendations for the prevention and treatment of vitamin D deficiency in children and adults in Poland have been developed by a team of scientists representing Polish and international medical societies and national specialist consultants. Their consensus, by Prof. Paweł Płudowski and the whole team has just been published in the journal „Nutrients” (https://doi.org/10.3390/nu15030695).

The development of the current guidelines was supported by prof. Carsten Carlberg, researcher of vitamin D, currently the leader of the scientific group dealing with nutrigenomics at the Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences in Olsztyn.

„We cannot rely on diet as the only source of vitamin D – even a balanced and varied one is not enough, so in the autumn and winter everyone should supplement vitamin D” – indicated Prof. Carlberg as the most important message of the publication.

The most well-known action of vitamin D is to maintain an adequate level of calcium in the body to maintain normal bone structure. „This is the main reason why every child should be supplemented with vitamin D from birth – both in winter and summer. In addition, vitamin D is important for training our immune system to work effectively against microbial infections, but not overreacted to possible autoimmune reactions” – explained Prof. Carlberg.

Long-term vitamin D deficiency can lead to bone diseases – rickets in children and osteomalacia in adults. „Vitamin D deficiency also causes malfunction of the immune system, leading to increased susceptibility to infectious diseases or autoimmune diseases” – the researcher pointed out.

Prof. Carlberg added that for the average Pole, the level of vitamin D (i.e. the level of 25-hydroxyvitamin D3 in the blood serum) determining the deficiency is defined below 50 nM (20 ng/ml), although each person is characterized by a different sensitivity to vitamin D.

It has been scientifically proven that even a balanced and varied diet is not able to provide the total daily dose of the body’s demand for vitamin D, because its main source is skin synthesis in contact with UV radiation. However, as the scientists pointed, spending a lot of time indoors, wearing clothes and using sunscreens, as well as low intensity of solar radiation in the autumn and winter months, translates into numerous vitamin D deficiencies during this time.

Therefore, a well-chosen supplementation is crucial. „I suggest choosing the dose of the daily requirement based on body weight – if you weigh up to 75 kg, take 2000 units daily (in the autumn and winter), and if more – 4000 units (but not more; this is the maximum dose)” – advises Prof. Carlberg.

In turn, in the spring and summer months, from April to September, it is worth exposing the skin to the sun (remembering about adequate protection against sunburn). „The time of day is important. Two hours before and after the sun’s zenith (11am-3pm in summer time) are most effective. During this time, 20-30 minutes of exposure of the face and bare shoulders should be enough. Of course, avoiding sunburn each time ” – said Prof. Carlberg.

The scientist added that people who do not spend enough time outdoors even in summer should supplement vitamin D throughout the year.

In the developed guidelines, experts pay particular attention to the need for education in the field of vitamin D supplementation for preventive purposes, addressed primarily to medical societies, medical personnel and decision makers responsible for health policy. They also postulate the inclusion of practical tips on the prevention and treatment of vitamin D deficiency in everyday practice.

Scientists visit the Olsztyn Planetarium

Another extraordinary meeting with the Olsztyn Children’s Academy is behind us. This time the young students were met by Dr. Anna Szóstek-Mioduchowska, who talked about an issue of particular importance in the autumn-winter season – the immune system. Dr. Szóstek-Mioduchowska drew attention to the human body’s 'tools’ for defending itself against harmful external and internal factors. What immune cells do we find in the human body and how many are there in one drop of blood? What is the difference between innate and acquired immunity? What does the body tell us when we are affected by ailments characterised by inflammation? Answers to these and many other questions were sought during the meeting.

The students were also treated to a workshop session where they could play young chemists’ roles. Under the supervision of Kamila Penkacik, M.Sc., the children studied magical antioxidants and created molecular pearls.

The third meeting of the Academy took place on 11 February at Olsztyn’s Planetarium. The next is planned for 15 April. More information about the Olsztyn Children’s Academy can be found on the Planetarium website under the Education tab.

The Genome above the Genome – Prof. Carsten Carlberg, ERA Chair WELCOME2

Our daily diet contains carbohydrates, lipids, proteins, minerals, and vitamins – nutrients that provide us with energy and serve as the building blocks of our bodies. However, we are increasingly learning that what we eat also interacts with the genes in our cells in important ways.

Diet is the most dominant of the environmental factors affecting us from conception to death. Every day, more than 1 kg of food passes through our bodies, the largest amount of all substances we come into close contact with. Dietary signals are in direct contact with the genome: every day, our breakfast, lunch, and dinner “talk” to our genes. For more than 20 years, we have known the sequence of all 20,000 human genes that carry the information needed to build proteins. We also know that in addition to them, there are at least as many non-coding RNAs within our genome, which do not produce any proteins. This understanding has brought us into the postgenomic era, where research has been initiated in numerous new fields. These include nutrigenomics, which can be defined as the study of how the food we eat (“nutri”) interacts with all of our genes (“genomics”).

The same yet different

Nearly 99% of the genome differs very little among all 8 billion humans on Earth. However, we do differ from one another in terms of such obvious traits as height, weight, hair, and skin and eye color, as well as such characteristics as the likelihood of developing a specific disease. Some of these traits, such as eye color, are obviously determined by genes. However, the risk of developing type 2 diabetes, for example, is only up to 10% determined by the genes we inherit from our parents and up to 90% determined by environmental factors and our lifestyle.

Our body is made up of 3×1013 cells, which come in at least 400 different variants. They form the tissues of the brain, the immune system, the liver, and all other organs in the body. In every human, each cell contains the same genome, which means the same information necessary to build proteins. In different types of cells, however, the genome is organized by proteins into tightly packed chromatin (called heterochromatin) and lightly packed chromatin (euchromatin) in such a way that access is only possible to those genes that carry information about the proteins needed in specific tissues. This packing of the genome, which does not affect its DNA sequence (it does not cause any mutations), is referred to as the “epigenome” (“epi-” meaning “above”).

Some aspects of the epigenome become fixed already in the first weeks of gestation, referred to as early embryogenesis. In this very sensitive period of life, important decisions are made about the development of organs, which should remain unchanged for the rest of the organism’s life. It is this stable part of the epigenome that ensures that our brain cells remain brain cells throughout our lives, instead of “changing their minds” and suddenly transforming, for example, into kidney cells that produce urine. The integrity of the human body is based on the stability of this aspect of the epigenome.

But the epigenome has also certain dynamic aspects: signals from the inside and outside of cells affect the ability of specialized proteins in the nucleus to recognize certain regions of the genome. Certain signals, for example those from food components, can alter how the genome is packaged into euchromatin and heterochromatin. Genes located in euchromatin can be recognized by transcription factors and RNA polymerases. This means that a specific cell uses only those of the 20,000 genes that it can access through the chromatin structure. This means an average of 10,000 genes that get copied out into RNA (in a process called transcription), which is used by a particular cell as a “template” to synthesize proteins. Changes in the epigenome can affect the transcriptome, or the total number of RNA molecules in our cells. Many of the signals that affect the epigenome and the transcriptome come from diet. Therefore, a central aspect of nutrigenomic research involves describing and understanding how nutrients affect the epigenome and the transcriptome of cells, and by the same token their functions. This aspect of nutrigenomics is often referred to as nutritional epigenomics.

Every day, the dietary choices we make impact on the epigenome and the transcriptome in our tissues and cell types. A disease like type 2 diabetes takes years or even decades to develop, but it results above all from daily diet and lifestyle choices. In a similar way, other elements of what is called the metabolic syndrome, such as high blood pressure, abdominal obesity (measured by waist circumference), high levels of fat (triglycerides), and low levels of HDL (high-density lipoprotein, also referred to as the “good” cholesterol) in the blood, depend on the decisions we make – what we eat and how much we exercise.

Benefits of vitamin D3

The compounds that can “talk” to the epigenome include vitamin D3. In fact, this is a nutrient we are able to produce within our bodies, through skin exposure to UVB radiation from the Sun. However, predominantly indoor lifestyles, skin coverage with textiles, the use of sunscreens, as well as the insufficient intensity of sunlight in the winter months mean that many people acquire vitamin D3 deficiency. Vitamin D status is measured by the blood serum concentration of the most abundant vitamin D3 metabolite, namely 25-hydroxyvitamin D3 (abbreviated 25(OH)D3). According to the US-based Endocrine Society, vitamin D status should be at least 75 nM (ideally 100 nM), whereas concentrations of 25(OH)D3 below 50 nM are regarded as deficiency, and below 30 nM as severe deficiency. More than 1 billion people worldwide have vitamin D deficiency. To put this into perspective, the average vitamin D status in the population in Poland is estimated at 46 nM, which means that many people in the country suffer from a deficiency of this compound and require supplementation, especially in the winter months.

However, one might ask whether the threshold level for the vitamin D status is the best benchmark for calculating the demand for vitamin D in individual people. Every human is different, and the impact of vitamin D on the response of the epigenome and the transcriptome in our cells will vary. Based on our concept of the vitamin D response index, people can be divided into high, mid, and low responders to vitamin D. It is estimated that one in four people fall into the group of low responders. This therefore means that we have our own individual requirements for vitamin D3 supplementation, especially during the winter months. High responders have lower needs and are likely to manage with the generally recommended, yet low concentrations: up to 20 μg, or 800 international units (IU) per day. Low responders, on the other hand, may need up to 4,000 IU (100 μg) per day.

Vitamin D is well known for its role in controlling calcium levels in blood. It is essential for bone remodelling; a process takes place throughout our lives. Children with vitamin D deficiency can develop rickets, and adults can be affected by osteomalacia, a deformation of the bones that carries a higher risk of fractures. In addition, vitamin D is extremely important for the proper functioning of the immune system, which comprises innate and adaptive immunity. The innate immune system is the first line of defence against microbial pathogens such as bacteria and viruses. In addition, cells of the innate immune system, such as monocytes, macrophages, and neutrophils, are key mediators of inflammation. Inflammation can be divided into acute and chronic. Acute inflammation lasts up to two weeks and supports the body in the fight against pathogens. In chronic inflammation, the cause of this harmful state is not removed successfully, and adverse reactions continue for months, years, or even decades. Most of the serious diseases, such as type 2 diabetes, atherosclerosis, Alzheimer’s disease and cancer, are associated with chronic inflammation. In the short term, vitamin D supports acute inflammation, but in the long term, it counteracts chronic inflammation. This chiefly happens through the “programming” of the epigenome and the transcriptome of monocytes and macrophages. These epigenetic programming events create cellular memory, which means that cells remember what they were exposed to. In a similar way, all the cells in our bodies (not just the neurons in the brain) can remember lifestyle-related events, such as daily responses to food components, physical activity, and exposure to pathogens.

A step towards personalized medicine

Our projects are based upon the central assumption that vitamin D trains immune cells and other tissue cells so that they can better respond to various environmental factors. In the context of the Horizon 2020-funded ERA Chair WELCOME2 project, we will be conducting an intervention study. Sixty volunteers with early signs and symptoms of metabolicsyndrome will be asked to make significant lifestyle changes for a period of three months. We will ask them to increase their average daily physical activity, for example by increasing the number of steps per day to at least 10,000. We will simultaneously give all participants vitamin D until they reach a very good status of 100 nM. In addition, we plan to follow up 10 highly committed participants for a period of three years and take their blood samples every three months. We will use their immune cells (obtained from the blood samples) to characterize their epigenome and transcriptome and observe how they change together with lifestyle changes. In this way, we will collect huge amounts of molecular data from each participant. We will analyse such data using bioinformatics methods, including machine learning.

A key point of our project will involve the development of computer models called digital twins. The concept of a “digital twin” is well-known in engineering, for example in aircraft construction. It stands to reason that all aircraft components, such as engines and wings, must undergo extensive tests, both individually and in combination with other components, to ensure that the aircraft will pose no risk to the pilot and passengers. Such tests are currently carried out using digital computer models, which can simulate a much broader range of conditions than traditional wind tunnels. Digital twins of real people are a lot more complex than aircraft engines. Therefore, it is necessary to be realistic and strive to model only certain tissues and cell types. Consequently, we will create digital twins of monocytes and lymphocytes isolated from blood samples taken from specific participants. Unlike other tissues in the human body, such immune cells have one advantage: they are mobile. Monocytes and lymphocytes circulate through the body, communicating with all organs. As a consequence, immune cells respond to all changes in the body and, supported by vitamin D, train their epigenome accordingly.

Importantly, digital twins not only facilitate computational descriptions of cell functions, but also offer the ability to test such factors as stress, infections, and exposure to food components. As with aircraft engines, we can also try out various interventions in silico, which means testing multiple factors in a computer model without the need to involve study participants. This means reducing their effort and exposure to danger, and saving funds. Since each individual is different, our digital twins will be idiosyncratic in nature, too. Consequently, we expect to obtain personalized recommendations for lifestyle changes for each study participant to reduce the risk of the development or progression of the metabolic syndrome. Since some of the conclusions from the modelling of these digital twins will be general in nature, we will attempt to apply the results we will obtain in the study to the general population.

This article was originally published in ACADEMIA – The magazine of the Polish Academy of Sciences | 2022 | No 3 (75) Turning Points

Publication by Dr. Agnieszka Wacławik’s team selected as Editor’s Choice

The publication by the team of Dr. Agnieszka Wacławik from the Department of Hormone Mechanisms, entitled „Novel role for conceptus signals in mRNA expression regulation by DNA methylation in porcine endometrium during early pregnancy” by P. Kaczyński, V. van der Weijden, E. Goryszewska-Szczurek, M. Baryly, SE Ulbrich and A. Waclawik, was selected as ’Editor’s choice’ in the prestigious journal Biology of Reproduction 2023, 108(1): 150-168.

’Edtitor’s choice’ publications are articles that have made a significant contribution to a field of science. The selection of an article as an 'Editor’s choice’ recognises the authors’ work and highlights the importance of their research in the field of reproductive biology.

Dr. Piotr Kaczyński and the authors mentioned above have described a novel mechanism of embryonic effects on processes related to methylation changes in DNA sequences that may regulate the expression of genes in the endometrium that are important for the development of pregnancy. The findings, published in the journal Biology of Reproduction (2023, 108(1): 150-168, doi: 10.1093/biolre/ioac193), were produced within the framework of the NCN OPUS project (2017/27/B/NZ9/03014) under the direction of Dr. Agnieszka Wacławik, carried out at our Institute and during the internship of Dr. Piotr Kaczyński in the team of Prof S. Ulbrich at the ETH Zurich.

Evolution, human migrations, and vitamin D deficiencies

When did organisms learn to synthesize vitamin D? How did its functions change throughout our evolution, and how did this affect the entire Homo sapiens species? Professor Carsten Carlberg answers these questions in his latest scientific publication.

A new publication by Prof. Carsten Carlberg, ERA Chair in the WELCOME2 project at the Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences, titled „Vitamin D in the Context of Evolution,” has appeared in the journal Nutrients. The „career” of vitamin D goes back to as early as 1.2 billion years ago, when eukaryotes (organisms with cell nuclei) developed the ability to synthesize sterols (and therefore vitamin D). In his publication, Prof. Carlberg explains how in the course of evolution – including that of the Homo sapiens – the role of vitamin D changed over time and „stabilized” relatively recently.

It wasn’t until 100 years ago that vitamin D was called a „vitamin” because its administration could cure experimentally induced rickets in dogs and rats. Rickets is also a developmental disorder in children, and many studies have linked vitamin D to calcium homeostasis and bone remodeling. It quickly became apparent that this is only one of many processes controlled by this micronutrient – others include detoxification, energy metabolism, and innate immunity. Researchers also point to a possible role for vitamin D in skin lightening among migrating peoples, particularly in European populations.

How did vitamin D become a vitamin?

Evolution is the basic process responsible for the biological development of all living organisms. There are no animals or plants on Earth that are not subject to the laws of evolution and thus do not adapt to environmental changes. In Prof. Carlberg’s paper, we read that one such adaptation was the development in animals ca. 550 million years ago, the Vitamin D Receptor (VDR), which transports proteins and enzymes for vitamin D metabolism.

Initially, vitamin D regulated physiological processes, the first of which was detoxification and energy metabolism. Thus, vitamin D modulated the energy-intensive processes of the innate immune system in its fight against microbes. In his latest work, Prof. Carlberg mentions that about 400 million years ago, species left the ocean and were exposed to gravity. Vitamin D took on the additional role of a master regulator of calcium homeostasis, essential for a stable skeleton.

„In its evolutionary origin in East Africa, the Homo sapiens species was exposed to extensive UV-B radiation every day all year round, which induced sufficient vitamin D₃ synthesis. Therefore, over 200,000 years, humans have become accustomed to a consistently high vitamin D status of 100 nM 25(OH)D₃ or more. Over the past 50,000-75,000 years, migration toward regions with latitudes above 37oN has allowed them to experience seasonal changes in sun exposure and periods of the year when vitamin D₃ cannot be produced endogenously,” according to Prof. Carlberg’s publication.

As a result of the industrial revolution, people have adapted to an urban lifestyle with predominant work and indoor activity. Both conditions – winters with vitamin D and indoor preferences – often led to vitamin D deficiency in industrialized countries. In the 19th century, rickets was common among children in England, and vitamin D deficiencies increased tuberculosis in many countries. In a published paper, Prof. Carlberg concludes that it was not evolution but human migrations and lifestyle changes that made vitamin D₃ a vitamin.

Quite recently – on an evolutionary scale – human lifestyle changes have caused a decrease in endogenous vitamin D₃ production. At the same time, most of the population is not based on a Mediterranean diet, so they are vitamin D deficient. Worldwide, this problem affects over a billion people and causes numerous health problems, including bone deformities and reduced immune system performance.

Prof. Carlberg’s unique publication

This work by Prof. Carlberg sheds new light on the evolutionary mechanisms that led to the development of the VDR receptor, enabling vitamin D uptake. He also shows that it is not the evolutionary process but lifestyle changes and frequent migrations that are the reason for the vitamin D deficiencies occurring around the world today, which affect most of us.

The paper, „Vitamin D in the Context of Evolution,” also allowed Prof. Carlberg to cross another critical threshold: reaching H-index 60 on the Publons platform. It provides a service for scientists to track, verify and present their scientific reviews and editorial contributions to scientific journals. It is worth mentioning that Prof. Carlberg already has 265 publications on Publons, which have been cited nearly 12,000 times.

Prof. Carlberg’s main task within the ERA Chair WELCOME2 project at the Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences is to create a team dedicated to analyzing gene regulation on the scale of the entire human genome, in particular changes in the human epigenome. This will be aided, among other things, by the development of „digital twins,” or virtual models of healthy and sick individuals, allowing in silico (via computer simulation) testing of interventions related to diet selection, physical activity, and drug use. These activities will form the basis of the Center of Excellence in nutrigenomics at the Institute. You can read more about the ERA Chair WELCOME2 project here.