In 2012 it has been 60 years from the 1952 Summer Olympics in Helsinki. Outstanding marathon run of Emil Zatopek was one of the most memorable events in the 1952 Olympics. Our own, European Champion and Boston marathon winner, Veikko Karvonen finished in the 4th place.
It's late November and pubmed allready offers us a possibility to see latest on immune tolerance and inflammation collected nicely by scientists from the Rockefeller University in N.Y.
The mucosal surface of the intestine alone forms the largest area exposed to exogenous antigens as well as the largest collection of lymphoid tissue in the body. The enormous amount of nonpathogenic and pathogenic bacteria and food-derived antigens that we are daily exposed sets an interesting challenge to the immune system: a protective immune activity must coexist with efficient regulatory mechanisms in order to maintain a health status of these organisms.
Interface between the Outside and Inside Environments
The intestinal mucosa forms the largest area of the body in direct contact with the exterior environment. If expanded, the surface of the small intestine alone can reach roughly the size of a tennis court, or 100 times the area of the skin. In the skin, several layers of cells, including stratified epidermis, and dermis, generate a physical barrier that separates the internal components of the body from the outside. On the other hand, in the intestine, a single layer of absorptive epithelial cells forms an interface between the lumen (outside environment) and the lamina propria (inside environment). If one sees our body as a target for attack from infectious and pathogenic organisms, the structure of intestinal epithelia is counterintuitive, since the intestine is exposed to constant colonization by bacteria and is a host to an enormous quantity and diversity of microbes, including commensals and potential pathogens. More than 100 trillion microbial cells colonize the human gut, which amounts to ten bacteria for every one human cell. The vast majority of these bacteria are not pathogenic, but rather perform a variety of beneficial functions to the host. A recent study estimated that the human microbiome contains more than 1000 bacterial species, with more than 160 different species generally present in each person. These results highlight a high degree of person-to-person variation, possibly influenced by a distinct host genetic landscape and environmental conditions.
Other mucosal surfaces also harbor a diverse microbiota. For instance, over 200 genera of bacteria were identified in a human skin microbiome study. However, the intestinal mucosa is peculiar since it has to deal with intense bacterial colonization and at the same time absorption and digestion of nutrients. In that regard, it should be noted that the large intestine contains most of the microbiota while the small intestine is the main place for absorption and digestion of nutrients.
In addition to the exposure to innocuous antigens, the intestine is also a place where many different types of infections can occur, including infection by viruses, bacteria, parasites, and fungi. Commensal bacteria, generally involved in symbiotic interactions with the host, have also been correlated with the development of inflammatory bowel diseases such as ulcerative colitis and Crohn’s disease. Similarly, dietary proteins can trigger food allergies and celiac disease. Therefore, it is reasonable to argue that the great majority of processes in the gut are not generated towards “defense” against invading organisms, but are rather a consequence of chronic exposure to large amounts of harmless and often beneficial antigens. This scenario poses an interesting challenge to the immune system, since most of the “nonself” interactions should probably be tolerized as “self”. How does the immune system associated with the intestine influence and assimilate the perturbations from the environment without generating pathology?
The Intestinal Context: Microbiota
Commensal microorganisms actively interact with the absorptive intestinal mucosa and influence the basal activity of the immune system as well as the amplitude of the immune response. The microbiota is able to modulate the activity of innate immune cells, including antigen presenting cells and innate lymphoid cells, in the lamina propria. Commensal bacteria-derived ATP has been shown to directly activate lamina propria T cells to produce IL-6, IL-23, and TGF-β and induce local differentiation of Th17 cells.
A contrasting example of a bacterial metabolite that contributes to the mucosal immunity is the short-chain fatty acids (SCFAs), which is produced by fermentation of dietary fiber . SCFAs bind to G-protein-coupled receptor 43 (GPR43, also known as FFAR2) and inhibit inflammatory responses during DSS-induced colitis by suppressing the differentiation of IL-17 producing cells in the lamina propria of conventional mice, suggesting that germ-free mice are more susceptible to this model of colitis due to reduced SCFA in the intestinal environment
The commensal bacteria Bacteroides fragilis is associated with suppression of Th17 and other inflammatory responses in the intestine by expression of polysaccharide A (PSA) via IL-10 production. A recent study showed that PSA is recognized by TLR2-expresing T cells and promotes their production of IL-10. Furthermore, PSA-treated Tregs are more efficient at suppressing activated T-cells in vitro, and Bacteroides fragilis mono-colonized recipient-mice induce higher numbers of Treg cells and show reduced Th17 responses after naïve CD4 adoptive transfer. In a recent report by Atarashi and coworkers identified Clostridium spp., a genus of gram-positive bacteria, belonging to the Firmicutes phylum, as a major inducer of Tregs in the colon of conventional mice. These results show that microbial-derived mechanisms can affect both innate and adaptive immunities and promote immune-regulation in the intestinal surface.
The Intestinal Context: Diet
Although much of the focus in mucosal immunology in recent years was given to the microbiota, most of the immune system antigen interaction in the gut is associated with the small intestine, where the nutrients are absorbed.
Beside the microbiota, the exposure to food proteins has also been shown to play a crucial role in the development and maintenance of the intestinal immune system as well as in susceptibility to systemic infection. The importance of food proteins to systemic immunity can also be appreciated by the fact that we ingest around 100 grams of protein daily, and up to 0.5% (500 mg/day) of ingested proteins can be found intact in blood circulation a few hours after ingestion.
Similarly to the microbiota, food proteins are potentially immunogenic and help to maintain the “immunological tonus”. Nevertheless, in general, the exposure to dietary antigens does not generate pathological responses. Indeed, mucosal exposure to antigens efficiently inhibits the development of immune responses to subsequent challenges with the same antigen, a phenomenon described as oral tolerance. It was demonstrated that peripheral generation of Foxp3-expressing Treg cells by TGF-β is a crucial event in oral tolerance induction in mice harboring monoclonal repertoire by both B and T cells (TBmc). Moreover, using the same experimental model, Curotto de Lafaille et al. showed that lack of functional Foxp3 results in abrogation of oral tolerance induction.
In addition to their regulatory role, it was also demonstrated that mucosal DCs from mesenteric lymph nodes (MLNs) and Peyer’s Patches (PPs) are unique in their capacity of degrading vitamin A to generate retinoic acid (RA). RA, in a TGF-β-dependent process, was proposed to play a crucial role in iTreg induction, demonstrating that diet-derived factors are also part of immune regulatory mechanisms involved in the prevention of aberrant immune responses towards the diet itself and other environmental antigens.
When oral tolerance is abolished, inflammatory processes generally arise resulting in the development of food allergies and other diseases. An example of food-related gut disorder is celiac (or coeliac) disease (CD), a condition that damages the lining of the small intestine and prevents it from absorbing nutrients. The damage is due to a lack of tolerance to gluten, a group of proteins found in wheat, barley, rye, and possibly oats. The break in tolerance leads to an exacerbated (mostly) Th1 immune response to specific gluten antigens (gliadin) in the small intestine after ingestion of gluten. The genetic background together with the intestinal context, in which the gluten protein is presented to T-cells, are the main factors in the balance between tolerance and inflammation in CD development. The differentiation of pathogenic, rather than regulatory, CD4+ T cells is thought to be induced by proinflammatory cytokines, including IL-15 and IFN-α, that are present in the intestinal mucosa from celiac disease patients.
Concluding remarks for the beginning of the year 2012
The dilemma faced by the mucosal immune system to induce tolerance to antigens (rule) or to engage an inflammatory immune response (exception) is daily dealt with through multidirectional interactions between the immune cells and environmental factors that permeate the mucosal surfaces. The identification of cellular and molecular mechanisms involved in this process will likely contribute to new approaches for prevention and treatment of systemic inflammatory diseases.
Friday, November 25, 2011
Thursday, November 24, 2011
Tales from The Land of Never Rising Sun
Parts of Finland are completely without sunlight throughout the winter months but luckily Northern Lights help us travel trough the darkness:
T1D is an autoimmune disease characterized by lymphocytic infiltration of the pancreatic islets, culminating in specific destruction of insulin-producing β cells. This immunological process unfolds over a variable number of years, resulting in clinically detectable hyperglycemia and, ultimately, diagnosis of diabetes. In vitro, vitamin D acts as an immunosuppressive agent, reducing lymphocyte proliferation and cytokine production. Furthermore, in animals, the oral administration of biologically active vitamin D3 metabolite (1,25[OH]2D3) seems to prevent development of type 1 diabetes.
The first prospective study of vitamin D3 supplementation in infants and type 1 diabetes was published in 2001 by Hyppönen et al. Among infants who were given supplements regularly, diabetes risk was lower at doses of over 50 µg/d or 2000 IU/d (relative risk 0.14) and exactly 50 µg/d (relative risk 0.22) compared with doses under 50 µg/d. This quite large, well-designed, prospective study provided compelling evidence that vitamin D3 supplementation of 50 µg/d (2000 IU/d) or more during infancy may reduce the risk for type 1 diabetes, at least in very northern parts of the world where sunlight is severely limited during a greater part of the year. In 2001 the recommended daily allowance of vitamin D3 in Finland for infants was about one tenth of what it was in the 1960s.
According to a systematic review and meta-analysis from 2008 vitamin D3 supplementation in early childhood may offer protection against the development of type 1 diabetes. The evidence for this is based on observational studies. While we are waiting randomised controlled trials with long enough periods of follow-up for possible causality we can address this interesting issue from another direction, through the GI tract.
______________________________
The incidence of type-1 diabetes in NOD mice is thought to reflect the degree of cleanliness of the colony. A widely accepted extrapolation from these data has been that NOD mice maintained under germ-free conditions have an increased incidence of diabetes. New studies has confirmed that idea wrong and instead support the notion that modulation of intestinal microbiota can have beneficial effects on the development of autoimmune diabetes.
______________________________
In 2011 Alam et al from the University of Turku presented evidence that young NOD mice suffer from a mild level of colitis, which disrupts the immune homeostasis of the large intestine. Intolerance to autologous microbiota, colonic hyperplasia, increased numbers of dendritic cells, and increased levels of IL-17 and IL-23 in the NOD colon are all indicative of colonic inflammatory activity. Remarkably, this condition is alleviated if the standard mouse diet is changed to an antidiabetogenic diet (ProSobee) from the time of weaning. It is thought that the intestinal immune system of newly weaned individuals may be particularly sensitive to immune disruption due to the yet immature immune system, higher permeability of the intestinal wall, and lower numbers of IgA positive B-cells in infancy.
How does this intestinal inflammation connect to first stone in the wall, vitamin D3, and the T1D protection seen in the animal studies?
Vitamin D receptor (VDR) is a nuclear receptor that mediates most known functions of 1,25-dihydroxyvitamin D3 (1,25[OH]2D3), the hormonal form of vitamin D. In recent study it was demonstrated that commensal and pathogenic bacteria directly regulate colonic epithelial VDR expression and location in vivo. VDR negatively regulates bacterial-induced intestinal NF-κB activation and attenuates response to infection. Therefore, VDR is an important contributor to intestinal homeostasis and host protection from bacterial invasion and infection.
So there it is for chewing. Could vitamin D3 be a brick in a wall or is it just giving some ideas what may be going on?
T1D is an autoimmune disease characterized by lymphocytic infiltration of the pancreatic islets, culminating in specific destruction of insulin-producing β cells. This immunological process unfolds over a variable number of years, resulting in clinically detectable hyperglycemia and, ultimately, diagnosis of diabetes. In vitro, vitamin D acts as an immunosuppressive agent, reducing lymphocyte proliferation and cytokine production. Furthermore, in animals, the oral administration of biologically active vitamin D3 metabolite (1,25[OH]2D3) seems to prevent development of type 1 diabetes.
The first prospective study of vitamin D3 supplementation in infants and type 1 diabetes was published in 2001 by Hyppönen et al. Among infants who were given supplements regularly, diabetes risk was lower at doses of over 50 µg/d or 2000 IU/d (relative risk 0.14) and exactly 50 µg/d (relative risk 0.22) compared with doses under 50 µg/d. This quite large, well-designed, prospective study provided compelling evidence that vitamin D3 supplementation of 50 µg/d (2000 IU/d) or more during infancy may reduce the risk for type 1 diabetes, at least in very northern parts of the world where sunlight is severely limited during a greater part of the year. In 2001 the recommended daily allowance of vitamin D3 in Finland for infants was about one tenth of what it was in the 1960s.
According to a systematic review and meta-analysis from 2008 vitamin D3 supplementation in early childhood may offer protection against the development of type 1 diabetes. The evidence for this is based on observational studies. While we are waiting randomised controlled trials with long enough periods of follow-up for possible causality we can address this interesting issue from another direction, through the GI tract.
______________________________
As we've learnt earlier environmental factors seem to be behind increased prevalence of T1D and dietary and microbial factors may be partly responsible for this increase. Evidence suggesting that gut immune disruptions may trigger type 1 diabetes originated from studies that showed correlations between a high prevalence of cow-milk antibodies, brief breastfeeding in infancy, and an increased risk of type 1 diabetes. This hypothesis gained further support from the discovery that lymphocytes accumulating in the islets share homing characteristics with gut-associated lymphocytes.
The development of the postnatal immune system is guided by the interactions of lymphocytes with self-MHC/peptide ligands derived from our body's own tissues and those from the environment, such as the commensal microbial flora of the gastrointestinal tract and the diet.The intestinal mucosa is constantly exposed to these factors, and it is therefore important to thoroughly understand how these factors affect the intestinal immune system.
The way in which antigenic stimulation guides the development and maintenance of a healthy immune system is of fundamental importance to our understanding of immunological tolerance. In the non-obese diabetic (NOD) mouse strain, the target pancreatic insulin producing beta cells are attacked and destroyed by activated immune cells, leading to type-1 diabetes. Several infectious, and non-infectious agents are known to prevent type-1 diabetes in NOD mice. Stimulation with adjuvant containing bacterial extracts in the neonatal period is known to prevent diabetes and imparts qualitative and quantitative changes in the immune cell compartments that lasts throughout adulthood. There has been a number of hypotheses presented that could account for the protective effect of immunostimulation such as a change in the cytokine milieu and the increase in T cell numbers or populations of regulatory T cells.
The development of the postnatal immune system is guided by the interactions of lymphocytes with self-MHC/peptide ligands derived from our body's own tissues and those from the environment, such as the commensal microbial flora of the gastrointestinal tract and the diet.The intestinal mucosa is constantly exposed to these factors, and it is therefore important to thoroughly understand how these factors affect the intestinal immune system.
The way in which antigenic stimulation guides the development and maintenance of a healthy immune system is of fundamental importance to our understanding of immunological tolerance. In the non-obese diabetic (NOD) mouse strain, the target pancreatic insulin producing beta cells are attacked and destroyed by activated immune cells, leading to type-1 diabetes. Several infectious, and non-infectious agents are known to prevent type-1 diabetes in NOD mice. Stimulation with adjuvant containing bacterial extracts in the neonatal period is known to prevent diabetes and imparts qualitative and quantitative changes in the immune cell compartments that lasts throughout adulthood. There has been a number of hypotheses presented that could account for the protective effect of immunostimulation such as a change in the cytokine milieu and the increase in T cell numbers or populations of regulatory T cells.
The incidence of type-1 diabetes in NOD mice is thought to reflect the degree of cleanliness of the colony. A widely accepted extrapolation from these data has been that NOD mice maintained under germ-free conditions have an increased incidence of diabetes. New studies has confirmed that idea wrong and instead support the notion that modulation of intestinal microbiota can have beneficial effects on the development of autoimmune diabetes.
______________________________
In 2011 Alam et al from the University of Turku presented evidence that young NOD mice suffer from a mild level of colitis, which disrupts the immune homeostasis of the large intestine. Intolerance to autologous microbiota, colonic hyperplasia, increased numbers of dendritic cells, and increased levels of IL-17 and IL-23 in the NOD colon are all indicative of colonic inflammatory activity. Remarkably, this condition is alleviated if the standard mouse diet is changed to an antidiabetogenic diet (ProSobee) from the time of weaning. It is thought that the intestinal immune system of newly weaned individuals may be particularly sensitive to immune disruption due to the yet immature immune system, higher permeability of the intestinal wall, and lower numbers of IgA positive B-cells in infancy.
The evidence brought forward in Alam et al emphasizes the importance of the colonic immune system and the role of microbial prevalence in the development of type 1 diabetes in the NOD model. They suggested that the antidiabetogenic effects of the ProSobee diet derive, at least in part, from its capacity to restore colonic immune homeostasis in NOD, where a proinflammatory bias otherwise prevails. The anti-inflammatory effects of the ProSobee diet also have implications outside of the gastrointestinal immune system, because it changes the properties of the peritoneal B-cells. It was proposed that the colonic immune imbalance in NOD mice reflects on the peritoneal immune cells, which subsequently aid in initiating an autoimmune response in the pancreatic lymph nodes, triggering type 1 diabetes development which was alleviated by diet.
How does this intestinal inflammation connect to first stone in the wall, vitamin D3, and the T1D protection seen in the animal studies?
Vitamin D receptor (VDR) is a nuclear receptor that mediates most known functions of 1,25-dihydroxyvitamin D3 (1,25[OH]2D3), the hormonal form of vitamin D. In recent study it was demonstrated that commensal and pathogenic bacteria directly regulate colonic epithelial VDR expression and location in vivo. VDR negatively regulates bacterial-induced intestinal NF-κB activation and attenuates response to infection. Therefore, VDR is an important contributor to intestinal homeostasis and host protection from bacterial invasion and infection.
So there it is for chewing. Could vitamin D3 be a brick in a wall or is it just giving some ideas what may be going on?
Sunday, November 20, 2011
Lessons to be Learnt from the Little Pigs
In my previous post it was stated that T1D is caused by loss of insulin-secreting capacity of the β cells and, finally, by selective death of these cells in the islets of Langerhans in the pancreas.That offers interesting area for drug development due to its complexity and high economical potential but it has only limited or near zero value for understanding the causative factors behind the disease. If we would like to learn more about the reasons or causes behind the increased incidence of T1D we have to take a closer look at the environmental factors connected to diabetes and try to find answers that are urgently needed around the globe.
In the medical literature environment has often been seen as a hostile disease provoking thing with viruses, pathogenic microbes, toxins or pollution. Chronic inflammatory diseases are usually looked from this perpective too. At the case of T1D extendive amound of work has been done in identifying triggering factors like dietary antigens or microbial derived β cell cytolytic toxins.
Let's take a moment and recall the story of the Big Bad Wolf and Three Little Pigs:
T1D and promoting environmental factors was seen as Mr. Wolf, genetically approriate food for the Mr. Wolf as Piglets, protective environmental factors between poor little genetics and T1D as building materials.
In the light of this educational story wouldn't it be kind of stupid if we put all the money, time and energy in figuring out why Mr. Wolf is a wolf and what makes him interested in eating little pink piglets? What if we just acknowledged that wolf does what it does because it is a wolf? It is in it's nature. If we try to completely wipe out piglet eating wolfs (antigens, viruses etc.) from the earth other problems will emerge. Instead of wolf hunting we could aim our efforts into protective building materials with a goal to protect little piglets as good as possible despite of the presence of the wolf.
Let's try to find the bricks that'll help piglets to survive!
In the medical literature environment has often been seen as a hostile disease provoking thing with viruses, pathogenic microbes, toxins or pollution. Chronic inflammatory diseases are usually looked from this perpective too. At the case of T1D extendive amound of work has been done in identifying triggering factors like dietary antigens or microbial derived β cell cytolytic toxins.
Let's take a moment and recall the story of the Big Bad Wolf and Three Little Pigs:
T1D and promoting environmental factors was seen as Mr. Wolf, genetically approriate food for the Mr. Wolf as Piglets, protective environmental factors between poor little genetics and T1D as building materials.
In the light of this educational story wouldn't it be kind of stupid if we put all the money, time and energy in figuring out why Mr. Wolf is a wolf and what makes him interested in eating little pink piglets? What if we just acknowledged that wolf does what it does because it is a wolf? It is in it's nature. If we try to completely wipe out piglet eating wolfs (antigens, viruses etc.) from the earth other problems will emerge. Instead of wolf hunting we could aim our efforts into protective building materials with a goal to protect little piglets as good as possible despite of the presence of the wolf.
Let's try to find the bricks that'll help piglets to survive!
Saturday, November 19, 2011
Finland: Ice Hockey World Champion 2011 and World Leader in T1DM Incidence
Ice Hockey World Championships 2011 will be membered from amazing goal by Mikael Granlund against Russia at the semifinals.
Type 1 diabetes (T1D) is the most common metabolic-endocrine disorder in children in western countries. Finland has the highest incidence of T1D in the world. Moreover, the incidence has increased more five-fold in Finland over the last sixty years; from 12/100000 in 1953, to 64.2/100000 in 2005.
T1D is caused by loss of insulin-secreting capacity of the β cells and, finally, by selective death of these cells in the islets of Langerhans in the pancreas. T1D is an autoimmune disease characterized by a relatively long symptom-free period that precedes the flair-up of clinical signs of the disease. In almost all children, progression to clinical T1D is associated with the presence of β cell specific autoantibodies. Clinical T1D occurs when 80-90% of the β cells have been destroyed. At this point T1D patient is dependent on a daily insulin substitution for the rest of his/her life and there is a high risk of developing acute and long-term complications.
An individual’s genetic makeup is known to influence the likelihood for developing diabetes. It is nevertheless evident, that regardless of the multiple loci associated to T1D, the impact of genetics on T1D aetiology is limited. In fact a family history of T1D only serves to increase the risk of T1D, and even in monozygotic twins, the proband-wise concordance for T1D is as low as fifty per cent. It is also argued, that the increase in magnitude in T1D incidence over a relatively short space of time cannot be attributed solely to enhanced genetic disease susceptibility. The pathogenesis of human T1D is under genetic as well as environmental control, and it is plausible that environmental factors play a notable role in increased disease prevalence.
Nowadays it is widely accepted that dietary and microbial factors may be partly responsible for the increase in T1D incidence. These two factors are closely related, since the diet has a direct effect on microbial species prevalence in the intestine. In many diseases, including T1D, the reasons behind microbial-dependent disorders seem to come down to an induction of inflammation in the gut epithelium and/ or increased permeability of the intestinal wall.
List of suspected dietary triggers of T1D is atleast partly quite surprising:
- vegetables, root vegetables and berries
- cow milk proteins
- wheat and barley proteins
The role of viral infections as a trigger for T1D in humans has been studied extensively. Amongst the viruses that have been suggested to confer an increased T1D risk are enteroviruses (in particular coxsackie virus B), rubella virus, mumps virus, rota virus, retrovirus, cytomegalovirus and Epstein-Barr virus. The correlation between viral infections and T1D incidence has, however, not been eminent in all studies and it has also been argued that atleast enterovirus infections are not likely to be the cause of the increase in T1D incidence, since these infections are much less common in Finland compared with Russia, despite the significantly higher T1D incidence in Finland.
Fundamentally, whatever the environmental triggers will be, they are likely to be something we are exposed to early on in childhood. This is because the greatest increase in T1D incidence has been observed in children diagnosed under 5 years of age, and the earliest signs of autoimmunity become evident under one year of age.
Road trip has begun...
Type 1 diabetes (T1D) is the most common metabolic-endocrine disorder in children in western countries. Finland has the highest incidence of T1D in the world. Moreover, the incidence has increased more five-fold in Finland over the last sixty years; from 12/100000 in 1953, to 64.2/100000 in 2005.
T1D is caused by loss of insulin-secreting capacity of the β cells and, finally, by selective death of these cells in the islets of Langerhans in the pancreas. T1D is an autoimmune disease characterized by a relatively long symptom-free period that precedes the flair-up of clinical signs of the disease. In almost all children, progression to clinical T1D is associated with the presence of β cell specific autoantibodies. Clinical T1D occurs when 80-90% of the β cells have been destroyed. At this point T1D patient is dependent on a daily insulin substitution for the rest of his/her life and there is a high risk of developing acute and long-term complications.
An individual’s genetic makeup is known to influence the likelihood for developing diabetes. It is nevertheless evident, that regardless of the multiple loci associated to T1D, the impact of genetics on T1D aetiology is limited. In fact a family history of T1D only serves to increase the risk of T1D, and even in monozygotic twins, the proband-wise concordance for T1D is as low as fifty per cent. It is also argued, that the increase in magnitude in T1D incidence over a relatively short space of time cannot be attributed solely to enhanced genetic disease susceptibility. The pathogenesis of human T1D is under genetic as well as environmental control, and it is plausible that environmental factors play a notable role in increased disease prevalence.
Nowadays it is widely accepted that dietary and microbial factors may be partly responsible for the increase in T1D incidence. These two factors are closely related, since the diet has a direct effect on microbial species prevalence in the intestine. In many diseases, including T1D, the reasons behind microbial-dependent disorders seem to come down to an induction of inflammation in the gut epithelium and/ or increased permeability of the intestinal wall.
List of suspected dietary triggers of T1D is atleast partly quite surprising:
- vegetables, root vegetables and berries
- cow milk proteins
- wheat and barley proteins
The role of viral infections as a trigger for T1D in humans has been studied extensively. Amongst the viruses that have been suggested to confer an increased T1D risk are enteroviruses (in particular coxsackie virus B), rubella virus, mumps virus, rota virus, retrovirus, cytomegalovirus and Epstein-Barr virus. The correlation between viral infections and T1D incidence has, however, not been eminent in all studies and it has also been argued that atleast enterovirus infections are not likely to be the cause of the increase in T1D incidence, since these infections are much less common in Finland compared with Russia, despite the significantly higher T1D incidence in Finland.
Fundamentally, whatever the environmental triggers will be, they are likely to be something we are exposed to early on in childhood. This is because the greatest increase in T1D incidence has been observed in children diagnosed under 5 years of age, and the earliest signs of autoimmunity become evident under one year of age.
Road trip has begun...
Autoimmunity knockout blog is here!
Autoimmunity knockout blog will dig deep down to the science behind nasty chronic diseases which are a result of an interaction between genetics and environment.
Time will tell if it has anything new to offer. Enjoy! :)
Time will tell if it has anything new to offer. Enjoy! :)
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