Developments in celiac disease and wheat-sensitivity disorders

 

Celiac disease remained a rare disease until this century. “When I went to medical school, people from Ireland, the Netherlands, and other Northern Europeans had celiac disease. The prevalence of celiac disease has increased in the United States and worldwide.

AGA Institute

The clinical expression of celiac disease has also changed over time. “In the past century, celiac disease was an overt malabsorptive condition with diarrhea, a low body mass index, bone disease, malnutrition, infertility, and anemia but atypical celiac disease is now common, with non-GI presentations including neurological problems, depression, and migraines. Many patients also lack an overt clinical manifestation – the so-called “silent celiac disase,” which is often detected during screening of first-degree relatives and other at-risk patients.

Advances have been made in the understanding of celiac disease pathogenesis over the past few decades regarding the host genotype, currently restricted to the HLA genes, the delivery mode of gluten, type of feeding, time of feeding, and possibly antibiotics modulating the microbiome. The DQ2 genes are necessary but are insufficient to explain the development of celiac disease. About 40% of the burden of celiac disease is related to the HLA-DQ2.2, 2.5, and 8 genes. In spite of many genomewide association studies, no key molecules have been identified that play a significant role in causing the disease to date.

The association of enteric infections and celiac disease may explain why genetically susceptible individuals that are exposed to gluten from childhood do not all develop the disease in early childhood. The average age of diagnosis of celiac disease in modern times is the mid-40s, and the individuals have been eating gluten all their lives, so it’s not clear why and when people develop celiac disease. It has been postulated that enteric infection could modulate the immune system, cause breaches in the mucosal barrier, and alters of the microbiome, thus triggering the disease. A study recently published in Science supports the role of reovirus as a trigger for celiac disease and results from the TEDDY study group published in Clinical Gastroenterology and Hepatology suggest that rotavirus vaccination could reduce celiac disease autoimmunity in susceptible children.

While the mechanisms underlying nonceliac gluten sensitivity or wheat sensitivity are still unclear, the terms “encompass individuals who report symptoms or alterations in health that are related to perceived gluten or wheat ingestion.” These symptoms could stem from fructose or fructans in wheat starch (FODMAPs), which could lead to symptoms similar to irritable bowel syndrome or other functional GI disorders. North American data show that more and more people without a diagnosis of celiac disease are consuming gluten-free products. Researchers have postulated that the pathophysiology of these conditions could include activation of the innate immune system, increased permeability, mucosal inflammation, basophil and eosinophil activation, antigliadin antibody elevation, and wheat amyloid trypsin inhibitors, but data have been inconsistent. The recommendation for diagnosing nonceliac gluten or wheat sensitivity is a double-blind placebo-controlled gluten trial to assess gluten-induced symptoms after excluding celiac disease or wheat allergy, but this testing is rarely available in North America. A recent study published in Clinical Gastroenterology and Hepatology demonstrated the limitations of this testing. The gluten-free diet is now very popular, but some drawbacks have emerged. These include an increased risk for cardiovascular disorders linked to the diet according to a recent study published in BMJ, and increased levels of heavy metals in urine and blood found in insecticide used on rice, according to a recent study published in Epidemiology. Further studies are needed to corroborate these recall diet studies.
 

Dr. Crowe is a clinical professor of medicine in the department of gastroenterology, University of California, San Diego. She reports financial relationships with UpToDate, Ferring, and Otsuka. She made her comments during the AGA Institute Presidential Plenary at the Annual Digestive Disease Week.

 

Celiac disease remained a rare disease until this century. “When I went to medical school, people from Ireland, the Netherlands, and other Northern Europeans had celiac disease. The prevalence of celiac disease has increased in the United States and worldwide.

AGA Institute

The clinical expression of celiac disease has also changed over time. “In the past century, celiac disease was an overt malabsorptive condition with diarrhea, a low body mass index, bone disease, malnutrition, infertility, and anemia but atypical celiac disease is now common, with non-GI presentations including neurological problems, depression, and migraines. Many patients also lack an overt clinical manifestation – the so-called “silent celiac disase,” which is often detected during screening of first-degree relatives and other at-risk patients.

Advances have been made in the understanding of celiac disease pathogenesis over the past few decades regarding the host genotype, currently restricted to the HLA genes, the delivery mode of gluten, type of feeding, time of feeding, and possibly antibiotics modulating the microbiome. The DQ2 genes are necessary but are insufficient to explain the development of celiac disease. About 40% of the burden of celiac disease is related to the HLA-DQ2.2, 2.5, and 8 genes. In spite of many genomewide association studies, no key molecules have been identified that play a significant role in causing the disease to date.

The association of enteric infections and celiac disease may explain why genetically susceptible individuals that are exposed to gluten from childhood do not all develop the disease in early childhood. The average age of diagnosis of celiac disease in modern times is the mid-40s, and the individuals have been eating gluten all their lives, so it’s not clear why and when people develop celiac disease. It has been postulated that enteric infection could modulate the immune system, cause breaches in the mucosal barrier, and alters of the microbiome, thus triggering the disease. A study recently published in Science supports the role of reovirus as a trigger for celiac disease and results from the TEDDY study group published in Clinical Gastroenterology and Hepatology suggest that rotavirus vaccination could reduce celiac disease autoimmunity in susceptible children.

While the mechanisms underlying nonceliac gluten sensitivity or wheat sensitivity are still unclear, the terms “encompass individuals who report symptoms or alterations in health that are related to perceived gluten or wheat ingestion.” These symptoms could stem from fructose or fructans in wheat starch (FODMAPs), which could lead to symptoms similar to irritable bowel syndrome or other functional GI disorders. North American data show that more and more people without a diagnosis of celiac disease are consuming gluten-free products. Researchers have postulated that the pathophysiology of these conditions could include activation of the innate immune system, increased permeability, mucosal inflammation, basophil and eosinophil activation, antigliadin antibody elevation, and wheat amyloid trypsin inhibitors, but data have been inconsistent. The recommendation for diagnosing nonceliac gluten or wheat sensitivity is a double-blind placebo-controlled gluten trial to assess gluten-induced symptoms after excluding celiac disease or wheat allergy, but this testing is rarely available in North America. A recent study published in Clinical Gastroenterology and Hepatology demonstrated the limitations of this testing. The gluten-free diet is now very popular, but some drawbacks have emerged. These include an increased risk for cardiovascular disorders linked to the diet according to a recent study published in BMJ, and increased levels of heavy metals in urine and blood found in insecticide used on rice, according to a recent study published in Epidemiology. Further studies are needed to corroborate these recall diet studies.
 

Dr. Crowe is a clinical professor of medicine in the department of gastroenterology, University of California, San Diego. She reports financial relationships with UpToDate, Ferring, and Otsuka. She made her comments during the AGA Institute Presidential Plenary at the Annual Digestive Disease Week.

 

Celiac disease remained a rare disease until this century. “When I went to medical school, people from Ireland, the Netherlands, and other Northern Europeans had celiac disease. The prevalence of celiac disease has increased in the United States and worldwide.

AGA Institute

The clinical expression of celiac disease has also changed over time. “In the past century, celiac disease was an overt malabsorptive condition with diarrhea, a low body mass index, bone disease, malnutrition, infertility, and anemia but atypical celiac disease is now common, with non-GI presentations including neurological problems, depression, and migraines. Many patients also lack an overt clinical manifestation – the so-called “silent celiac disase,” which is often detected during screening of first-degree relatives and other at-risk patients.

Advances have been made in the understanding of celiac disease pathogenesis over the past few decades regarding the host genotype, currently restricted to the HLA genes, the delivery mode of gluten, type of feeding, time of feeding, and possibly antibiotics modulating the microbiome. The DQ2 genes are necessary but are insufficient to explain the development of celiac disease. About 40% of the burden of celiac disease is related to the HLA-DQ2.2, 2.5, and 8 genes. In spite of many genomewide association studies, no key molecules have been identified that play a significant role in causing the disease to date.

The association of enteric infections and celiac disease may explain why genetically susceptible individuals that are exposed to gluten from childhood do not all develop the disease in early childhood. The average age of diagnosis of celiac disease in modern times is the mid-40s, and the individuals have been eating gluten all their lives, so it’s not clear why and when people develop celiac disease. It has been postulated that enteric infection could modulate the immune system, cause breaches in the mucosal barrier, and alters of the microbiome, thus triggering the disease. A study recently published in Science supports the role of reovirus as a trigger for celiac disease and results from the TEDDY study group published in Clinical Gastroenterology and Hepatology suggest that rotavirus vaccination could reduce celiac disease autoimmunity in susceptible children.

While the mechanisms underlying nonceliac gluten sensitivity or wheat sensitivity are still unclear, the terms “encompass individuals who report symptoms or alterations in health that are related to perceived gluten or wheat ingestion.” These symptoms could stem from fructose or fructans in wheat starch (FODMAPs), which could lead to symptoms similar to irritable bowel syndrome or other functional GI disorders. North American data show that more and more people without a diagnosis of celiac disease are consuming gluten-free products. Researchers have postulated that the pathophysiology of these conditions could include activation of the innate immune system, increased permeability, mucosal inflammation, basophil and eosinophil activation, antigliadin antibody elevation, and wheat amyloid trypsin inhibitors, but data have been inconsistent. The recommendation for diagnosing nonceliac gluten or wheat sensitivity is a double-blind placebo-controlled gluten trial to assess gluten-induced symptoms after excluding celiac disease or wheat allergy, but this testing is rarely available in North America. A recent study published in Clinical Gastroenterology and Hepatology demonstrated the limitations of this testing. The gluten-free diet is now very popular, but some drawbacks have emerged. These include an increased risk for cardiovascular disorders linked to the diet according to a recent study published in BMJ, and increased levels of heavy metals in urine and blood found in insecticide used on rice, according to a recent study published in Epidemiology. Further studies are needed to corroborate these recall diet studies.
 

Dr. Crowe is a clinical professor of medicine in the department of gastroenterology, University of California, San Diego. She reports financial relationships with UpToDate, Ferring, and Otsuka. She made her comments during the AGA Institute Presidential Plenary at the Annual Digestive Disease Week.