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Food, Hypersensitivies, Diets, Probiotics, Attitudes

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Advances in Autism Research
April 2010

Regarding diets, supplements, and pharmaceuticals, the Autism Research Institute's Parent Ratings of Behavioral Effects of Biomedical Interventions remains an informative resource for parents and physicians (1).  Diets data from parental observations in the Parent Ratings summaries are provided perspective by cites 2, 3, and 7. Probiotics may be helpful for some children with autism or other ASDs (eg, 8-16).

1. Parent Ratings of Behavorial Effects of Biomedical Interventions.  Since 1967 the Autism Research Institute has been collecting parent ratings of the usefulness of the many interventions tried on their autistic children.
http://www.autism.com/treatable/form34qr.htm

2. Food allergy knowledge, attitudes and beliefs: focus groups of parents, physicians and the general public
Gupta RS, Kim JS, Barnathan JA, Amsden LB, Tummala LS, Holl JL.
BMC Pediatr. 2008 Sep 19;8:36.
http://www.biomedcentral.com/1471-2431/8/36

BACKGROUND: Food allergy prevalence is increasing in US children. Presently, the primary means of preventing potentially fatal reactions are avoidance of allergens, prompt recognition of food allergy reactions, and knowledge about food allergy reaction treatments. Focus groups were held as a preliminary step in the development of validated survey instruments to assess food allergy knowledge, attitudes, and beliefs of parents, physicians, and the general public. METHODS: Eight focus groups were conducted between January and July of 2006 in the Chicago area with parents of children with food allergy (3 groups), physicians (3 groups), and the general public (2 groups). A constant comparative method was used to identify the emerging themes which were then grouped into key domains of food allergy knowledge, attitudes, and beliefs. RESULTS: Parents of children with food allergy had solid fundamental knowledge but had concerns about primary care physicians' knowledge of food allergy, diagnostic approaches, and treatment practices. The considerable impact of children's food allergies on familial quality of life was articulated. Physicians had good basic knowledge of food allergy but differed in their approach to diagnosis and advice about starting solids and breastfeeding. The general public had wide variation in knowledge about food allergy with many misconceptions of key concepts related to prevalence, definition, and triggers of food allergy. CONCLUSION: Appreciable food allergy knowledge gaps exist, especially among physicians and the general public. The quality of life for children with food allergy and their families is significantly affected.

3. Food allergy among children in the United States
Branum AM, Lukacs SL.
National Center for Health Statistics, CDC
Pediatrics. 2009 Dec;124(6):1549-55.
http://pediatrics.aappublications.org/cgi/reprint/124/6/1549

OBJECTIVES: The goals were to estimate the prevalence of food allergy and to describe trends in food allergy prevalence and health care use among US children. METHODS: A cross-sectional survey of data on food allergy among children <18 years of age, as reported in the 1997-2007 National Health Interview Survey, 2005-2006 National Health and Nutrition Examination Survey, 1993-2006 National Hospital Ambulatory Medical Care Survey and National Ambulatory Medical Care Survey, and 1998-2006 National Hospital Discharge Survey, was performed. Reported food allergies, serum immunoglobulin E antibody levels for specific foods, ambulatory care visits, and hospitalizations were assessed. RESULTS: In 2007, 3.9% of US children <18 years of age had reported food allergy. The prevalence of reported food allergy increased 18% (z = 3.4; P < .01) from 1997 through 2007. In 2005-2006, serum immunoglobulin E antibodies to peanut were detectable for an estimated 9% of US children. Ambulatory care visits tripled between 1993 and 2006 (P < .01). From 2003 through 2006, an estimated average of 317000 food allergy-related, ambulatory care visits per year (95% confidence interval: 195000-438000 visits per year) to emergency and outpatient departments and physician's offices were reported. Hospitalizations with any recorded diagnoses related to food allergy also increased between 1998-2000 and 2004-2006, from an average of 2600 discharges per year to 9500 discharges per year (z = 3.4; P < .01), possibly because of increased use of food allergy V codes. CONCLUSION: Several national health surveys indicate that food allergy prevalence and/or awareness has increased among US children in recent years.

4. Food allergy and autism spectrum disorders: is there a link?
Jyonouchi H.
Curr Allergy Asthma Rep. 2009 May;9(3):194-201.

Gastrointestinal (GI) symptoms are common comorbidities in children with autism spectrum disorders (ASDs). Parents often attribute these GI symptoms to food allergy (FA), although an evaluation for IgE-mediated FA is often unrevealing. Our previous studies indicated a high prevalence of non-IgE-mediated FA in young children with ASDs. Therefore, non-IgE-mediated FA may account for some but not all GI symptoms observed in children with ASDs. This raises the question of what treatment measures are applicable to ASD children with GI symptoms. A wide variety of dietary supplements and dietary intervention measures for ASD children have been promoted by medical professionals practicing complementary and alternative medicine despite the lack of rigorous scientific validation in most instances. This review summarizes possible (or proposed) etiologies of GI symptoms in ASD children and discusses risks and possible benefits of intervention measures promoted by complementary and alternative practitioners, with emphasis on FA.

5. A review of dietary interventions in autism
Srinivasan P.
Ann Clin Psychiatry. 2009 Oct-Dec;21(4):237-47.
https://www.aacp.com/Abstract.asp?AID=8148&issue=&page=C&UID=

BACKGROUND: Anecdotal reports and parent surveys have shown evidence that dietary interventions have had some success in ameliorating the symptoms of autism. METHODS: In this paper, key findings that prompt a dietary intervention strategy are reviewed and popular intervention diets are described. RESULTS: There is a significant body of literature pertinent to dietary interventions in autism from the perspectives of gastroenterology, immunology, and excitotoxicity. Some articles report benefits to patients on standardized rating scales. CONCLUSIONS: This article presents a survey of the literature related to dietary interventions studied in the context of autism as well as various hypotheses on the rationale for dietary interventions. Patients or caregivers increasingly are attempting such interventions. Further studies are needed to establish the efficacy of these diets, the patients who would best benefit from diets, the mechanism of action, and the role of diets in addition to other treatments.

6. Altered Sulfur Amino Acid Metabolism In Immune Cells of Children Diagnosed With Autism
Suh et al.
Children’s Hospital Oakland Research Institute
American Journal of Biochemistry and Biotechnology 4 (2): 105-113, 2008
http://www.scipub.org/fulltext/ajbb/ajbb42105-113.pdf

Autism Spectrum Disorder (ASD) is a behaviorally defined neurodevelopmental disorder whose etiology is poorly understood. Recent studies have shown that autistic children may be experiencing increased inflammation and oxidative stress. Altered immune regulation may be one contributing factor to inflammation and oxidative stress in autistic children. Sulfur amino acid (SAA) metabolism plays a critical role in regulating blood leukocyte functions and oxidative stress. However, it is not known whether autism impacts SAA metabolism in peripheral immune cells. To address this question, a novel liquid chromatography linked tandem mass spectrometric (LC/MS/MS) method was used to determine the levels of SAA metabolites in peripheral blood mononuclear cells obtained from 11 healthy controls and 31 autistic children. Improved detection sensitivity and selectivity of the LC/MS/MS method allowed accurate quantification using small samples. Results show that leukocytes from autistic children contained significantly lower concentrations of S-adenosylmethionine (-35%; p = 0.01), and elevated levels of intracellular homocysteine content (+80%; p=0.003). Additionally, the levels of intracellular total cysteine and glutathione (GSH) were reduced by 39% (p=0.004) and 25% (p=0.01), respectively. These autism-associated changes were leukocyte specific in that no significant alterations in SAA metabolite concentrations were detected in the plasma samples. Our results provide novel evidence for altered metabolism in immune cells; furthermore, this data suggest the involvement of inflammation in autism. Dietary differences between controls and patients, however, remain a potential confounder.

7. When doctors disagree: a qualitative study of doctors' and parents' views on the risks of childhood food allergy
Hu W, Grbich C, Kemp A.
Health Expect. 2008 Sep;11(3):208-19.
$ http://tinyurl.com/yalxp5d

OBJECTIVE: To examine the views of doctors which underpin clinical practice variation concerning an uncertain health risk, and the views of parents who had sought advice from these doctors, using the example of childhood food allergy. STUDY DESIGN: Qualitative study involving in-depth interviews and participant observation over 16 months. Focus groups and consultation audio-recordings provided corroborative data. SETTING: Three specialist allergy clinics located in one metropolitan area. PARTICIPANTS: Eighteen medical specialists and trainees in allergy, and 85 parents (from 69 families) with food allergic children. RESULTS: Doctors expressed a spectrum of views. The most divergent views were characterized by: scientific scepticism rather than precaution in response to uncertainty; emphasis on quantifiable physical evidence rather than parental histories; professional roles as providers of physical diagnosis and treatment rather than of information and advocacy; libertarian rather than communitarian perspectives on responsibility for risk; and values about allergy as a disease and normal childhood. Parents held a similar, but less divergent range of views. The majority of parents preferred more moderate doctors' views, with 43% (30 of 69) of families expressing their dissatisfaction by seeking another specialist opinion. Many were confused by variation in doctors' opinions, preferring relationships with doctors that recognized their concerns, addressed their information needs, and confirmed that they were managing their child's allergy appropriately. CONCLUSIONS: In uncertain clinical situations, parents do not expect absolute certainty from doctors; inflexible certainty may not allow parental preferences to be acknowledged or accommodated, and is associated with the seeking of second opinions.

8. Probiotics: delineation of prophylactic and therapeutic benefits
Kaur IP et al.
J Med Food. 2009 Apr;12(2):219-35.
http://www.liebertonline.com/doi/pdf/10.1089/jmf.2007.0544

Probiotics produce a beneficial impact on the host by improving the endogenous flora. It has been advocated that nonpathogenic bacteria like Lactobacillus and Bifidobacterium may undergo antagonistic interactions with other bacterial strains and can be used to control pathogenic bacteria. Novel modes of therapeutic and prophylactic interventions are based on their consumption either alone or in combination with prebiotics. Usefulness of probiotics has been implicated in allergies, cancer, AIDS, and respiratory and urinary tract infections. In this review we have listed various findings suggesting their benefits in alleviating symptoms associated with aging, fatigue, and autism. Newer claims indicating their role in reducing the risks of osteoporosis, obesity, and possibly type 2 diabetes are also discussed. Considering the wide array of such activities, the present review comprehensively elaborates upon the proposed benefits of probiotics. The concept of synbiotics, a combination of probiotics and prebiotics beneficially affecting the survival and implantation of such live organisms, is also discussed. Available probiotic strains, their commercial preparations, and newer approaches to improve the efficacy and overcome limitations of the therapy are also discussed in relation to the future of probiotic therapy. Considering that the purported claims about disease risk reduction are tentative, the review also encompasses various aspects regarding the safety of probiotics and their possible future role in disease prevention.

9. Probiotics promote gut health through stimulation of epithelial innate immunity
Cristiano Pagninia et al.
PNAS early edition, Dec 10, 2009
http://www.pnas.org/content/early/2009/12/10/0910307107.full.pdf+html

Probiotic formulations are widely available and have a variety of proposed beneficial effects, including promotion of gut health. The mechanisms of action of probiotic bacteria in the intestine are still unclear but are generally attributed to an antiinflammatory effect. Here,wedemonstrate that the multiple probiotic formulation VSL#3 prevents the onset of intestinal inflammation by local stimulation of epithelial innate immune responses (i.e., increased production of epithelial-derived TNF-α and restoration of epithelial barrier function in vivo). We also demonstrate that probiotic bacteria stimulate epithelial production of TNF-α and activate NF-κB in vitro. Our results support the hypothesis that probiotics promote gut health through stimulation, rather than suppression, of the innate immune system. Furthermore, our findings provide the perspective that defects in innate immunity may play a critical role in the pathogenesis and progression of intestinal disorders, such as inflammatory bowel disease.

10. Probiotics {review}
Gupta V, Garg R.
Indian J Med Microbiol. 2009 Jul-Sep;27(3):202-9.
http://tinyurl.com/yfqw4h3

The term "probiotic" was first used in 1965, by Lilly and Stillwell, to describe substances secreted by one organism which stimulate the growth of another. The use of antibiotics, immunosuppressive therapy and irradiation, amongst other means of treatment, may cause alterations in the composition and have an effect on the GIT flora. Therefore, the introduction of beneficial bacterial species to GI tract may be a very attractive option to re-establish the microbial equilibrium and prevent disease. Prebiotic is a non-digestible food ingredient that confers benefits on the host by selectively stimulating one bacterium or a group of bacteria in the colon with probiotic properties. Both probiotics and prebiotics are together called as Synbiotics. Various bacterial genera most commonly used in probiotic preparations are Lactobacillus, Bifidobacterium, Escherichia, Enterococcus, Bacillus and Streptococcus . Some fungal strains belonging to Saccharomyces have also been used. Probiotics have been shown to be effective in varied clinical conditions- ranging from infantile diarrhoea, necrotizing enterocolitis, antibiotic-associated diarrhoea, relapsing Clostridium difficle colitis, Helicobacter pylori infections, inflammatory bowel disease to cancer, female uro-genital infection and surgical infections. Lactobacillus rhamnosus strain GG has proven beneficial affects on intestinal immunity. It increases the number of IgA and other immunoglobulins secreting cells in the intestinal mucosa. It also stimulates local release of interferons. It facilitates antigen transport to underlying lymphoid cells, which serves to increase antigen uptake in Peyer's patches. Probiotics are live microorganisms, so it is possible that they may result in infection in the host. The risk and morbidity of sepsis due to probiotic bacteria should be weighed against the potential for sepsis due to more pathological bacteria and the morbidity of diseases for which probiotic bacteria are being used as therapeutic agents. Also, future, well-designed placebo controlled studies with validated results are required for ascertaining the true health benefits of probiotics The important point in this regard is careful selection of the probiotic agent, its dose standardization and a thorough knowledge of its beneficial effects.

11. Mechanisms of probiotic action: Implications for therapeutic applications in inflammatory bowel diseases
Vanderpool C, Yan F, Polk DB.
Vanderbilt University School of Medicine
Inflamm Bowel Dis. 2008 Nov;14(11):1585-96.
http://www3.interscience.wiley.com/cgi-bin/fulltext/120756832/PDFSTART

Probiotics are defined as nonpathogenic living microorganisms, including some commensal bacterial flora, which have beneficial effects on host health and disease prevention and/or treatment. Clinical trials have shown beneficial effects of probiotics on several human diseases, such as inflammatory bowel diseases (IBDs), which are among the most-studied diseases testing probiotics as a potential therapy. However, a significant question regarding clinical use of probiotics is the mechanism underlying the wide range of actions. Studies discussed in this review suggest 3 distinct cellular and molecular mechanisms for probiotic regulation in IBD therapy: 1) Probiotics block pathogenic bacterial effects by producing bactericidal substances and competing with pathogens and toxins for adherence to the intestinal epithelium; 2) Probiotics regulate immune responses by enhancing the innate immunity and modulating pathogen-induced inflammation via toll-like receptor-regulated signaling pathways; and 3) Probiotics regulate intestinal epithelial homeostasis by promoting intestinal epithelial cell survival, enhancing barrier function, and stimulating protective responses. Probiotics modulate host cell signaling pathways, including Akt, mitogen-activated protein kinases, and nuclear factor-kappaB to mediate these intestinal epithelial functions. It is hoped that developing a mechanistic understanding of probiotic action will provide the rationale to support the development of new hypothesis-driven studies to define the clinical efficacy in preventive, adjunctive, or alternative treatments for IBD.

12. Gut microbiota and probiotics in modulation of epithelium and gut-associated lymphoid tissue function
Sanz Y, De Palma G.
Int Rev Immunol. 2009;28(6):397-413.
http://www.ncbi.nlm.nih.gov/pubmed/19954356

The intestinal tract mucosa is exposed to a vast number of environmental antigens and a large community of commensal bacteria. The mucosal immune system has to provide both protection against pathogens and tolerance to harmless bacteria. Immune homeostasis depends on the interaction of indigenous commensal and transient bacteria (probiotics) with various components of the epithelium and the gut-associated lymphoid tissue. Herein, an update is given of the mechanisms by which the gut microbiota and probiotics are translocated through the epithelium, sensed via pattern-recognition receptors, and activate innate and adaptive immune responses.

13. The role of Probiotics in allergic diseases
Michail S.
Wright State University Boonshoft School of Medicine
Allergy Asthma Clin Immunol. 2009 Oct 22;5(1):5.
 http://www.aacijournal.com/content/5/1/5

Allergic disorders are very common in the pediatric age group. While the exact etiology is unclear, evidence is mounting to incriminate environmental factors and an aberrant gut microbiota with a shift of the Th1/Th2 balance towards a Th2 response. Probiotics have been shown to modulate the immune system back to a Th1 response. Several in vitro studies suggest a role for probiotics in treating allergic disorders. Human trials demonstrate a limited benefit for the use of probiotics in atopic dermatitis in a preventive as well as a therapeutic capacity. Data supporting their use in allergic rhinitis are less robust. Currently, there is no role for probiotic therapy in the treatment of bronchial asthma. Future studies will be critical in determining the exact role of probiotics in allergic disorders.

14. Probiotics and gastrointestinal disease: successes, problems and future prospects
Culligan EP, Hill C, Sleator RD.
Cork Institute of Technology
Gut Pathog. 2009 Nov 23;1(1):19.
http://www.gutpathogens.com/content/1/1/19

ABSTRACT: Gastrointestinal disease is a major cause of morbidity and mortality worldwide each year. Treatment of chronic inflammatory gastrointestinal conditions such as ulcerative colitis and Crohn's disease is difficult due to the ambiguity surrounding their precise aetiology. Infectious gastrointestinal diseases, such as various types of diarrheal disease are also becoming increasingly difficult to treat due to the increasing dissemination of antibiotic resistance among microorganisms and the emergence of the so-called 'superbugs'. Taking into consideration these problems, the need for novel therapeutics is essential. Although described for over a century probiotics have only been extensively researched in recent years. Their use in the treatment and prevention of disease, particularly gastrointestinal disease, has yielded many successful results, some of which we outline in this review. Although promising, many probiotics are hindered by inherent physiological and technological weaknesses and often the most clinically promising strains are unusable. Consequently we discuss various strategies whereby probiotics may be engineered to create designer probiotics. Such innovative approaches include; a receptor mimicry strategy to create probiotics that target specific pathogens and toxins, a patho-biotechnology approach using pathogen-derived genes to create more robust probiotic stains with increased host and processing-associated stress tolerance profiles and meta-biotechnology, whereby, functional metagenomics may be used to identify novel genes from diverse and vastly unexplored environments, such as the human gut, for use in biotechnology and medicine.

15. A case of D-lactic acid encephalopathy associated with use of probiotics
Munakata S, Arakawa C, Kohira R, Fujita Y, Fuchigami T, Mugishima H.
Department of Pediatrics, Nihon University School of Medicine, Tokyo, Japan.
Brain Dev. 2009 Nov 14. [Epub ahead of print]
http://www.ncbi.nlm.nih.gov/pubmed/19917522

A five year old girl was admitted to the hospital for evaluation of intermittent ataxia. She had undergone serial resections of the small intestine after birth, resulting in short bowel syndrome. Lactomin was prescribed for watery diarrhea at twice the regular dose 2weeks before the onset of neurologic symptoms. D-lactic acidosis was diagnosed on the basis of a plasma D-lactate level of 5.537mmol/l. Lactomin was discontinued, and she was treated with sodium bicarbonate and oral antibiotics. The probiotics the patient had taken were likely the cause of D-lactic acidosis and should therefore be avoided in patients with short bowel syndrome.

16. Gastroenteric pathology and probiotics: from myth to scientific evidence. Current aspects
Caramia G.
Salesi Specialized Hospital for Mothers and Children, Ancona, Italy
Minerva Gastroenterol Dietol. 2009 Sep;55(3):237-72.
http://www.ncbi.nlm.nih.gov/pubmed/19829283

Starting from Metchnikoff's theory of cell-mediated immunity and work on lactobacillus over 100 years ago, more and more applications for probiotics have been developed. Research into the health properties of probiotics has focused primarily on two areas: the interaction between intestinal microflora and enterocytes and the immune system and the use of probiotic products in the treatment of gastrointestinal diseases in adults and children. This review examines recent studies on the clinical use of monostrain and multistrain probiotic products in gastroenterology. The most widely studied strains are lactobacilli and yeasts, specifically, Lacto-bacillus rhamnosus GG and Saccharomices boulardii; the gastrointestinal disorders most commonly treated with probiotics are inflammatory bowel disease and dysbiosis, both of which clinically manifest as diarrhea.