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Posts Tagged ‘gastrointestinal’

‘The Doctors Are In’ Live Chat

February 29, 2012 1 comment

Please join us Thursday at 3 pm ET/noon PT for this month’s “The Doctors Are In” live webchat. Our featured guest will be pediatric dentist José Polido, D.D.S., head of dentistry at Children’s Hospital Los Angeles, one of our Autism Treatment Network centers.

Dr. Polido was instrumental in developing the newly released ATN tool kit for dental professionals. He welcomes your questions about dental issues including dental hygiene and visits to the dentist.

The live webchat will be hosted by Autism Speaks Head of Medical Research Joe Horrigan, M.D.

We hope you’ll join us!

What: “The Doctors Are In” webchat, with Drs. Horrigan and Polido
When: March 1 at 3 pm Eastern; 2 pm Central; 1 pm Mountain; noon Pacific
Where: Join via the Live Chat tab on left side of the Autism Speaks Facebook page

Autism and Associated Medical Conditions

January 24, 2012 18 comments

Guest post by epidemiologist Laura Schieve, Ph.D., of the National Center on Birth Defects and Developmental Disabilities, at the Centers for Disease Control and Prevention.

In recent years, several reports have suggested that children with autism or other learning or behavioral developmental disabilities are more likely than typically developing children to have health conditions such as respiratory or gastrointestinal illnesses.

However the studies behind these reports were often small and showed inconsistent findings. Some of their methods had limitations. One of the biggest problems was that they didn’t adequately compare children with different types of developmental disabilities. Because of these limitations, many public health professionals and healthcare providers have been skeptical about whether children with autism or other behavioral developmental disabilities truly faced an elevated risk of other medical problems.

My colleagues and I wanted to help paint a clearer picture of this important public health issue. Our study, recently published in the journal Research in Developmental Disabilities, compared the medical conditions and healthcare needs of children with developmental disabilities with those of children without developmental disabilities. We also compared children with autism with those who had other developmental disabilities.

We assessed children included in the National Health Interview Surveys from 2006 to 2010. Households throughout the United States are randomly selected to participate in this annual survey. In households with children, one child is randomly selected to participate. Each child’s parent or other primary caregiver is interviewed in-person about the child’s health and development. Interviewers asked whether a doctor or other healthcare provider has ever told them the child has certain conditions including autism and several other developmental disabilities. We also ask if the child has a health condition such as asthma or has experienced other symptoms such as frequent diarrhea or colitis in the past year.

We included more than 41,000 children aged 3 to 17 years in the study. Of these, 5,469 had one or more of the following five developmental disabilities:  autism, intellectual disability, attention deficit and hyperactivity disorder (ADHD), learning disability or other developmental delay.

As a group, these children had higher than expected rates of all of the medical conditions we studied. More specifically, they were:

* 1.8 times more likely than children without developmental disabilities to have ever had an asthma diagnosis,

* 1.6 times more likely to have had eczema or a skin allergy during the past year,

* 1.8 times more likely to have had a food allergy during the past year,

* 2.1 times more likely to have had three or more ear infections during the past year,

* 2.2 times more likely to have had frequent severe headaches or migraines during the past year, and

* 3.5 times more likely to have had frequent diarrhea or colitis during the past year.

These increased rates of health conditions held true even for children diagnosed with ADHD or learning disability, but not diagnosed with autism or intellectual disability.

However, one finding stood out in particular when we compared the developmental disability groups to each other: Children with autism were twice as likely as children with ADHD, learning disability or other developmental delay to have had frequent diarrhea or colitis during the past year. They were seven times more likely to have experienced these gastrointestinal problems than were children without any developmental disability.

This detailed assessment demonstrates that children with autism or many other types of developmental disabilities do, in fact, face an increased risk for many common health conditions. This, in turn, provides evidence that children with developmental disabilities require increased health services and specialist services, both for their core functional deficits and for health problems beyond their core developmental disabilities.

Reference: Schieve LA, Gonzales V, Boulet SL, Visser SN, Rice CE, Van Naarden-Braun K, Boyle CA. Concurrent medical conditions and health care use and needs among children with learning and behavioral developmental disabilities, National Health Interview Survey, 2006-2010.  Res Dev Disabil. 2011;33:467-76.

Read more autism research news and perspective on the science page. Explore the studies Autism Speaks is funding with our Grant Search. And thanks for making this research possible! 

How helpful is the casein-gluten-free diet?

November 11, 2011 58 comments

 This week’s answer comes from pediatric gastroenterologist, Kent Williams, MD, of Nationwide Children’s Hospital, in Columbus, Ohio—one of 17 sites in Autism Speaks’ Autism Treatment Network.

Many parents of children with autism spectrum disorders (ASDs) report that behavior improves when their children eat a diet free of the proteins gluten and casein. Gluten is found primarily in wheat, barley and rye; casein, in dairy products. Last year, clinicians within Autism Speaks Autism Treatment Network (ATN) investigated the issue and found insufficient evidence of clear benefit.  We called for clinical studies, and these studies are now underway.

While we’re awaiting the results, it’s reasonable to ask what harm could result from trying a casein-gluten-free diet. Certainly, dietary changes can be worth investigating and trying, and many parents report improvements in behavior.  However, until more clinical studies are completed and more evidence of safety and benefit is available, parents who place their child on a casein-gluten-free diet need to take extra steps to ensure they do so in a safe and reliable manner.

First, when parents decide to try a casein-gluten-free diet for their child, I strongly urge them to consult with a dietary counselor such as a nutritionist or dietician. Although it’s easy to find casein-gluten-free dietary plans on the Internet, few parents—or physicians—have the experience and knowledge to determine whether a child’s diet is providing all the necessary requirements for normal growth and development.  Keep in mind that foods containing gluten and casein are major sources of protein as well as essential vitamins and minerals such as vitamin D, calcium, and zinc.

I recommend that parents bring the nutritionist or dietician a 3- to 5-day dietary history for their child (writing down what was eaten and how much) and have this reviewed to determine whether there is a real risk for nutritional deficiency.  The nutritionist or dietician can then work with the family to add foods or supplements that address potential gaps in nutrition.

After establishing a plan for a safe and complete diet, I encourage parents to set up a reliable way to measure their child’s response to the diet. This should start before the diet is begun, with a list of the specific behaviors that the family would like to see improve. Examples might include angry outbursts, inability to sit quietly during class, problems sleeping at night, or not speaking to others.

Next recruit teachers, therapists, babysitters, and others outside the family to help you objectively monitor these targeted behaviors and verify your perception of changes. If you reach a consensus that improvements are occurring, continuing the diet may be worth the cost and effort.

However, one should still question whether the improvements are due to the removal of all gluten and casein from the diet.  The changes might be due to removal of just one of these proteins. For example, some parents report improvement with a casein-free diet, and others report improvements with gluten-free diets.

In fact, the behavioral changes may be due to dietary changes other than the removal of casein or gluten.  For example, the improvement might be due to the fact that the new diet replaces processed foods high in sugar and fat with healthier foods such as whole grain rice, fruits, and vegetables.

These alternative explanations are important to consider because a strict casein-gluten free diet requires hard work and can be costly.  For example, it may be difficult for your child to eat from the menus in a school cafeteria or restaurant. Birthday parties present another challenge. As a parent, you’ll likely be faced with the task of sending or bringing special meals and treats when your child eats away from home.

Autism Speaks ATN continues to support research and clinical improvement endeavors on nutritional and on gastrointestinal issues associated with autism through the HRSA-funded  Autism Intervention Network for Physical Health.

Have a question? Please email us at gotquestions@autismspeaks.org.  Read more news and perspective on the Autism Speaks science page.


New Insight into Autism and Intestinal Problems

September 19, 2011 6 comments

As parents have long reported, many children with autism experience severe gastrointestinal (GI) problems, and the associated discomfort can worsen behavior. Now research supported by Autism Speaks is lending new insight into how the GI activity of children with autism may differ from that of other children in key ways. Read more in the science news section at autismspeaks.org.

Intestine, Leaky Gut, and Autism: A Serendipitous Association of a Planned Design?

April 14, 2010 3 comments

We have asked several scientists who gave presentations at the April 10-11 DAN! conference in Baltimore to share their research and perspectives from the meeting with you here on the blog.  The following piece is from Dr. Alessio Fasano, M.D. Dr. Fasano is a Professor of Pediatrics and the Director of the Mucosal Biology Research Center at the University of Maryland.  Dr. Fasano also leads the Center for Celiac Research, which includes a multidisciplinary team of gastroenterologists, pediatricians, dieticians and nurses who work together to develop individualized treatment plans for people with Celiac Disease.

The Intestine and ASD

The human intestine is a deceptively complex organ.  It is lined by a single layer of cells exquisitely responsive to stimuli of innumerable variety, and is populated by a complex community of microbial partners, far more numerous than the cells of the intestine itself.  Under normal circumstances, these intestinal cells form a tight, but selective barrier to “friends and foes”: microbes and most environmental substances are held at bay, but nutrients from the essential to the trivial are absorbed efficiently (1,2).  Moreover, the tightness of the epithelial barrier is itself dynamic, though the mechanisms governing and effecting dynamic permeability are poorly understood.  What is becoming increasingly clear is that an intestinal barrier defect (i.e., leaky gut) is associated with a large number of local and systemic disorders, including Autism Spectrum Disorders (ASD) (3).

Regulation of Intestinal Permeability

Intestinal permeability is mainly dependent on the functional state of intercellular tight junctions, sort of gates between neighboring cells that regulate trafficking of molecules and cells from the external environment into our body. To meet the diverse physiological challenges to which the intestinal epithelial barrier is subjected, these gates must be capable of rapid and coordinated responses.  This requires the presence of a complex regulatory system that orchestrates the opening and closing of the gates between cells.  While knowledge of the gates’ composition and assembly has progressed significantly during the past decade, relatively little is known about their regulation in health and disease in response to exposure to a variety of environmental stimuli.  The discovery of zonulin, a molecule that reversibly modulates the gates’ opening, sheds light on how the intestinal barrier function is regulated in health and disease (4).  The two major environmental stimuli triggering the production of zonulin in the small intestine are the presence of microorganisms (i.e., proximal bowel contamination) and exposure to gluten.

New evidence suggests that this exaggerated production of zonulin is responsible, at least in part, for the leaky gut causing abnormal passage of gluten and other “bad guys”, including casein, underneath the gut cell lining (2). This uncontrolled access of substances that do not belong to our body may lead to the onset of autoimmune and inflammatory diseases, including ASD, in genetically predisposed individuals (2). [Read more more about autoimmune disorders and autism]

ASD and Diet

ASD are heterogeneous neurodevelopmental disorders that affect approximately 1% of the general population (5).  It is generally agreed that there are multiple causes for ASD, with both genetic and environmental components involved.  Gastrointestinal (GI) symptoms are frequently experienced by subjects with ASD, but their prevalence, nature and, therefore, best treatments remain elusive (6,7).  The most frequent GI symptoms experienced by subjects with ASD include constipation, gastroesophageal reflux, gastritis, intestinal inflammation (autistic entrocolitis), maldigestion, malabsorption, flatulence, abdominal pain or discomfort, lactose intolerance, enteric infections, among others.  Of the almost 50 complementary and alternative treatments proposed for ASD, seven (antifungal therapy, chelation, enzymes, GI treatments, intestinal parasite therapy, nutritional supplements, and dietary options for autism) are specifically focused to the GI tract.  It is worthwhile to note that in a recent informal survey conducted by the Autism Research Institute involving more than 27,000 parents of autistic kids, avoidance of gluten and/or casein were among the most frequent treatments implemented in their children, with a with a better:worse ratio of 30:1 and 32:1, respectively.

Intestine, Microbiome, and Leaky Gut

A possible unifying theory to “connect the dots” of all the factors mentioned above would link changes in the gut microorganism ecosystem with leaky gut, passage of digestion products of natural food such as bread and cow’s milk that would activate immune inflammatory cells that cause inflammation both in the intestine (autistic enterocolitis) and the brain (ASD).  Alternative to the inflammatory hypothesis, it has been proposed that the defect in the intestinal barrier in ASD patients allows passage of neuroactive peptides of food origin (gliadorphin and casomorphins) into the blood and then into the cerebrospinal fluid to interfere directly with the function of the CNS.  No matter which theory turns out to be correct, changes in the intestinal microbiome and the consequent leaky gut seem to be common denominators.

The Gluten Free Diet

Given the fact that ASD is a complex and heterogeneous condition, it is instrumental to stratify children affected by autism to identify subgroups that can benefit of specific therapeutic interventions, like a gluten free diet.  Therefore, it would be highly desirable to develop specific biomarkers to help identify who would benefit the most by implementing specific interventions, including the gluten free diet.  The ingestion by genetically susceptible individuals of gluten from wheat and of similar proteins present in barley and rye can cause immune reaction leading to small bowel inflammation.  It is the interplay between genes and the environmental triggers that leads to this inflammation. This inflammatory process is initially driven by special immune cells called neutrophils (a type of white blood cell), soldiers that are called immediately into the gut to fight the uncontrolled passage of invaders through the gates stuck open because of gluten-dependent zonulin release.  Once neutrophils intercept the invader, they try to eliminate it by causing inflammation that is not necessarily limited to the gut, since these “armed” immune cells can subsequently migrate in other tissues and organs, including skin, liver, joints, heart, and brain, causing inflammation also in the organs where they migrated.  Therefore, the strict avoidance of gluten-containing grains is the best approach to avoid these inflammatory processes that can be responsible of specific clinical outcomes, including ASD, in a subgroup of individuals genetically at risk to react to gluten.

Alternative Therapeutic Strategies

Alternative therapeutic strategies to a gluten-free diet include the oral use of the zonulin inhibitor larazotide and probiotics.  Larazotide, a sort of wax that blocks the hole in which the zonulin key locks in to open the gates in between intestinal cells, has already been successfully explored in an animal model of autoimmunity and, more recently and preliminarily, in celiac disease patients through double-blind, randomized, placebo-controlled human clinical trials (2). Probiotics are “good bacteria” typically found in dairy products like yogurt and are claimed to have several beneficial effects related to their capability of either reducing the risk or treating disease (8). Although the safety of probiotics naturally present in yogurt has never been in question, the more recent use of probiotics, like lactobacilli or bifidobacteria, delivered in high numbers to consumers with potentially compromised health has raised the question of safety.  The safety of these probiotics has been reviewed by qualified experts in the field. The general conclusion is that the potential of physiological harm of lactobacilli and bifidobacteria is quite low.  While the initial use of probiotics was based on anecdotal reports of their beneficial effects, we have more recently witnessed a series of more rigorously designed clinical trials documenting the potential use of probiotics for the treatment of a variety of pediatric disorders, including enteric infectious diseases, allergic and atopic disorders, and intestinal inflammatory diseases.   The two most studied probiotics are lactobacillus GG and bifidobacteria BB12, and there have been a large number of studies with these organisms in the pediatric population, whit consistent good safety data (ie., lack of side effects) but mixed efficacy (8). The inconsistent positive therapeutic results may be related to the fact that each probiotic organism has different effects, and, therefore, they cannot be used indiscriminately for each disorder.  Indeed, different conditions may be triggered by different microbiota composition and, therefore, may require different probiotics to be effectively treated.  By performing more detailed studies to link gut microbiota composition to certain conditions, such as ASD, we will be able to decipher the host-microbe cross-talk and, therefore, we will be able to customize probiotic treatment for specific conditions (i.e.; personalized medicine).

All the aforementioned therapeutic strategies are viable interventions and, therefore, it would be desirable to perform well-designed multi-center studies to stratify children with ASD to establish which subgroup of patients would benefit of these treatments.  This approach will allow customizing treatments to maximize the chance of success by targeting the subpopulation of ASD children that would benefit the most from a gluten free diet, the use of larazotide, or to choose the proper probiotic(s) to re-establish a healthy gut ecosystem capable to decrease or completely ameliorate the clinical presentations of ASD.

References

  1. Fasano A. Pathological and therapeutical implications of macromolecule passage through the tight junction. In Tight Junctions.  Boca Raton, FL:  CRC Press, Inc., 2001, p. 697-722.
  2. Fasano A. Physiological, pathological, and therapeutic implications of zonulin-mediated intestinal barrier modulation: living life on the edge of the wall. Am J Pathol.173:1243-52, 2008.
  3. White JF. Intestinal pathophysiology in Autism. Exp Biol Med 228:639–649, 2003.
  4. Wang W, Uzzau S, Goldblum SE, Fasano A. Human zonulin, a potential modulator of intestinal tight junctions. J Cell Sci 2000;113:4435-4440.
  5. Prevalence of autism spectrum disorders – Autism and Developmental Disabilities Monitoring Network, United States, 2006.Autism and Developmental Disabilities Monitoring Network Surveillance Year 2006 Principal Investigators; Centers for Disease Control and Prevention (CDC). MMWR Surveill Summ. 2009;58:1-20.
  6. Buie T, Campbell DB, Fuchs GJ, III, et al Evaluation, Diagnosis, and Treatment of Gastrointestinal Disorders in Individuals With ASDs: A Consensus Report. Pediatrics 2010;125;S1-S18.
  7. Buie T, Fuchs GJ, III, Furuta GT, Kooros K, Levy J, Lewis JD, Wershil BK, Winter H. Recommendations for Evaluation and Treatment of Common Gastrointestinal Problems in Children With ASDs. Pediatrics 2010;125;S19-S29
  8. Guarner F Prebiotics, probiotics and helminths: the ‘natural’ solution? Dig Dis. 2009;27:412-7. .
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5|25: Celebrating Five Years of Autism Science Day 23: Gastroenterology consensus recommendations provide recognition of the need for specialized approaches to GI problems in children with autism

February 23, 2010 1 comment

In honor of the anniversary of Autism Speaks’ founding on Feb 25, for the next 25 days we will be sharing stories about the many significant scientific advances that have occurred during our first five years together. Our 23rd item, Gastroenterology consensus recommendations provide recognition of the need for specialized approaches to GI problems in children with autism, is adapted from a 2009 press release. 

Gastrointestinal (GI) problems are a commonly expressed concern of parents of children with autism spectrum disorders (ASD), but families have often found it difficult to find appropriate care for these issues. In December 2009, a consensus statement and recommendations for the evaluation, diagnosis, and treatment of gastrointestinal disorders in children with ASD were published in Pediatrics. These recommendations are an important step in advancing physician awareness of the unique challenges in the medical management of children with autism and will be a prelude towards the development of evidence-based guidelines that will standardize care for all children with ASD. The reports highlighted the crucial need for information to guide care, and emphasized the critical importance of fostering more research in this area, including genetic research, to support the development of these guidelines.

“The Pediatrics paper represents long-sought recognition by the mainstream medical community that treatment of GI problems in children with autism requires specific and specialized approaches,” reacted Dr. Dawson. “Autism Speaks has been actively engaged in the study of GI problems associated with children with autism, working toward enhanced medical community awareness for over five years through its research agenda and the Autism Speaks’ Autism Treatment Network (ATN). Dan Coury, M.D., ATN medical director, commented, “We are delighted to see the publication of important information that can support clinicians and caregivers in providing better care for children with autism, particularly with GI concerns, as parents unfortunately very often find it difficult to identify physicians who have an understanding of these issues and are able to provide appropriate medical care for their children. GI and pediatric specialists from six of the ATN sites participated in the forum and in the development of these recommendations, which shows the power of interaction among the communities and individuals dedicated to this problem. Autism Speaks is already engaged in the crucial next step which is to move beyond these consensus-based recommendations to develop evidence-based clinical guidelines.” In addition to development of evidence-based clinical guidelines for GI issues, the ATN is also currently working on evidence based clinical guidelines for medical management of sleep, and neurologic disorders associated with autism. “Delivery of evidence-based clinical guidelines will serve as excellent opportunities for future training and education of physicians,” added Dr. Dawson.

The consensus statement highlights several important themes, the first emphasizing that GI problems are a genuine concern in the ASD population and that these disorders exacerbate or contribute to problem behaviors. The need for awareness of how GI problems manifest in children with autism and the potential for accompanying nutritional complications and impaired quality of life were also emphasized.

In the second paper, the authors make consensus recommendations providing guidance on how current general pediatric standards of care that can and should be applied for children with ASD. George Fuchs, M.D., a co-author on the two papers and chair of the ATN GI Committee remarked, “The recommendations provide important guidance for the clinician to adapt the current practices of care (for abdominal pain, chronic constipation and gastroesophageal reflux) for the child with autism. The recommendations from the Autism Forum meeting complement the ATN’s on-going work to develop evidence-based, ASD-specific guidelines. The ATN is currently piloting newly created guidelines and monitoring their effectiveness. We anticipate this data will contribute to an evidence-based foundation to support best practices for GI problems in ASD.”

Autism Speaks is committed to the sustained support of efforts that address co-morbid medical conditions in the ASD population. In recognizing that there’s not enough evidence in any GI area and more research is needed, the Pediatric papers reaffirm the importance of the recent November 2009, Autism Speaks sponsored symposium and workshop on Gastrointestinal Disorders in Autism Spectrum Disorders. The symposium and workshop represented an important partnership with the American Academy of Pediatrics, and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) – the largest professional society for GI and nutritional specialists, and a professional authority for the development and implementation of pediatric GI guidelines. The symposium raised awareness and provided the latest scientific information to an audience of 168 researchers, clinicians, and pediatric GI and nutrition specialists, most of whom had limited expertise in autism. The symposium was followed by a workshop that brought together a diverse group of experts in GI, nutrition, pediatrics, pain, ASD, and biological research. Recommendations were developed for an expanded and targeted research agenda for the field that will address current gaps in the knowledge base and aim to advance evaluation and treatment of ASD-GI disorders. Proceedings from the meeting are scheduled to be published in 2010. A unique and important element in both the Symposium and Workshop was the inclusion of parents of children with ASD.

Did you know?:  Autism Speaks’ Autism Treatment Network (ATN) is developing  evidence-based guidelines that will provide specific guidance to physicians on how to address a number of medical issues of concern for children with ASD.  The ATN is currently piloting a GI guideline algorithm (decision flow charts) for the assessment and treatment of constipation, and a sleep guideline algorithm for insomnia. The ATN is also working on guidelines in the areas of psychopharmacology and neurology. For more information on ATN guideline activities, please see www.autismspeaks.org/airp. 

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