Influence of candidate polymorphisms on the dipeptidyl peptidase IV and μ-opioid receptor genes expression in aspect of the β-casomorphin-7 modulation functions in autism

Cieślińska, Anna; Sienkiewicz-Szłapka, Edyta; Wasilewska, Jolanta; Fiedorowicz, Ewa; Chwała, Barbara; Moszyńska-Dumara, Małgorzata; Cieśliński, Tomasz; Bukało, Marta; Kostyra, Elżbieta

doi:10.1016/j.peptides.2014.11.012

Cited by 43 publications

(36 citation statements)

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“…In 1999, the role of β-casomorphin-7 (β-CM7 consisting of TyrPro-Phe-Pro-Gly-Pro-Ile) as an exogenous opioid released from β-casein in cow's milk and was described in relation to autism [63][64][65].…”

Section: β-Cm7 Opioid Peptides and Dpp4 Activitymentioning

confidence: 99%

“…• The β-CM7 peptide is degraded in the GI-tract by the hydrolyzing enzyme dipeptidyl peptidase IV (DPP4; EC 3.4.14.5), a process that is induced by microbiota [65][66][67][68][69].…”

Section: Citation: Cieślińska a Kostyra E Savelkoul Hfj (2017) Treamentioning

confidence: 99%

“…The β-CM7 peptide is known to be a µ-Opioid Receptor (MOR) agonist, and it can also interact with serotonin system, while eliciting comparable effects as the well-known narcotic pain relieving substance morphine [64][65][72][73][74][75]. In addition, there are also gluten-derived opioid peptides (exorphins like A4, A5, B4 and B537) that elicit similar effects in the brain through interaction with the δ-opioid receptor [76].…”

Section: Citation: Cieślińska a Kostyra E Savelkoul Hfj (2017) Treamentioning

confidence: 99%

“…DPP4 was studied as a dietary protein because it is found in the GI tract as a brush border enzyme. This enzyme is also found on immune cells and therefore coded as CD26 and plays a role in T-cell dependent immune responses while also displaying anti-inflammatory activity [66][67][68].The β-CM7 peptide is known to be a µ-Opioid Receptor (MOR) agonist, and it can also interact with serotonin system, while eliciting comparable effects as the well-known narcotic pain relieving substance morphine [64][65][72][73][74][75]. In addition, there are also gluten-derived opioid peptides (exorphins like A4, A5, B4 and B537) that elicit similar effects in the brain through interaction with the δ-opioid receptor [76].…”

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confidence: 99%

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2015

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There is a rising interest in the use of dietary interventions to ameliorate prevalent brain diseases, including Autism Spectrum Disorder (ASD). Nowadays, the existence of communication between gut and brain is well accepted and thus diet can influence brain functioning. A well-known nutrition based intervention for ASD is the gluten-free and casein-free diet. However, only some of the patients experience a relief in symptoms and thus efficacy seems to be limited to certain phenotypes. However, not much is known about the mechanism of action through which this diet might work, or about interpersonal differences that could lead to variation in response to the diet. Current evidence for efficacy of the GFCF diet is poor. Large scale, good quality randomized controlled trials are needed. Genetic and environmentally induced interpersonal differences were found in intestinal membrane permeability and blood brain barrier integrity as well as in activity of peptidase enzymes. These differences probably affect responsiveness to the diet. In addition, age and duration of the dietary intervention play a role in the efficacy of the gluten-free and casein-free diet. This is the reason why all these factors need to be taken into account to give appropriate advice about whether or not to follow this diet.Keywords: Autism spectrum disorder; Casein-free; Casomorphin; Diet; Gluten-free; Intervention; Opioid; Peptides; Permeability Treating Autism Spectrum Disorder with Gluten-free and Casein-free Diet: The underlying Microbiota-Gut-Brain Axis MechanismsCitation: Cieślińska A, Kostyra E, Savelkoul HFJ (2017) Treating Autism Spectrum Disorder with • (GFCF) diet is strongly promoted while there are additional diets without salicylates and phenols, and anti-candida diets since many ASD patients are affected by this yeast [17]. However, so far it has been difficult to prove the effectiveness of this diet in all patients [10,18]. Limited information is available on the underlying mechanism as well as explanatory factors of differences in response to the GFCF diet. Here, we focus on the mechanism of action underlying this dietary intervention as well as the origin of differences in response to the GFCF diet. Gluten-Free and Casein-Free Diet Might Alleviate Autism Spectrum Disorder SymptomsPeople with ASD are often in need of intensive care and guidance, leading to loss of parental productivity and high emotional and economic costs [8,19]. Therefore it is important to investigate potential treatments that alleviate the symptoms or preferably cure the disease. So far, sometimes life long, educational and behavioral interventions are used, although these therapies have limited efficacy for ASD [6,20]. Currently, there is growing interest in nutritional interventions for this disorder and there are promising mechanisms underlying the putative success of such interventions [19].In 1983 it was suggested that gluten and casein containing products could cause autism-like symptoms by altering the functioning of the brain. It was propo...

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Section: β-Cm7 Opioid Peptides and Dpp4 Activitymentioning

confidence: 99%

“…• The β-CM7 peptide is degraded in the GI-tract by the hydrolyzing enzyme dipeptidyl peptidase IV (DPP4; EC 3.4.14.5), a process that is induced by microbiota [65][66][67][68][69].…”

Section: Citation: Cieślińska a Kostyra E Savelkoul Hfj (2017) Treamentioning

confidence: 99%

Section: Citation: Cieślińska a Kostyra E Savelkoul Hfj (2017) Treamentioning

confidence: 99%

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2015

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“…Recent studies investigated the role of opioid peptides and intestinal permeability, 6 as well as alterations in the expression of certain genes. 7 Heberling et al 2 suggested that certain gut bacteria, oxidative stress and changes in intestinal permeability could be involved in the etiology of ASD.…”

Section: Introductionmentioning

confidence: 99%

Opioid peptides and gastrointestinal symptoms in autism spectrum disorders

Lázaro

Pondé

Rodrigues

2016

Rev. Bras. Psiquiatr.

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Autism spectrum disorders (ASDs) are characterized by deficits in the individual's ability to socialize, communicate, and use the imagination, in addition to stereotyped behaviors. These disorders have a heterogenous phenotype, both in relation to symptoms and regarding severity. Organic problems related to the gastrointestinal tract are often associated with ASD, including dysbiosis, inflammatory bowel disease, exocrine pancreatic insufficiency, celiac disease, indigestion, malabsorption, food intolerance, and food allergies, leading to vitamin deficiencies and malnutrition. In an attempt to explain the pathophysiology involved in autism, a theory founded on opioid excess has been the focus of various investigations, since it partially explains the symptomatology of the disorder. Another hypothesis has been put forward whereby the probable triggers of ASDs would be related to the presence of bacteria in the bowel, oxidative stress, and intestinal permeability. The present update reviews these hypotheses.

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