Peptides’ role in autism with emphasis on exorphins

Reichelt, Karl L.; Tveiten, Dag; Knivsberg, Ann‐Mari; Brønstad, Gunnar

doi:10.3402/mehd.v23i0.18958

Cited by 40 publications

(32 citation statements)

References 40 publications

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“…Food-derived opioid peptides are produced in the gut, where they can exert effects on the gut intestinal epithelium, but they can also enter the systemic circulation (42) and may be able to cross the blood-brain barrier (43). Recently, it has also been revealed that casein-derived opioid peptides are present in the urine of autistic and schizophrenic subjects, but not of controls (44,45).…”

Section: Discussionmentioning

confidence: 99%

Food-derived opioid peptides inhibit cysteine uptake with redox and epigenetic consequences

Trivedi

Shah

Al-Mughairy

et al. 2014

The Journal of Nutritional Biochemistry

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Dietary interventions like gluten-free and casein-free diets have been reported to improve intestinal, autoimmune and neurological symptoms in patients with a variety of conditions; however, the underlying mechanism of benefit for such diets remains unclear. Epigenetic programming, including CpG methylation and histone modifications, occurring during early postnatal development can influence the risk of disease in later life, and such programming may be modulated by nutritional factors such as milk and wheat, especially during the transition from a solely milk-based diet to one that includes other forms of nutrition. The hydrolytic digestion of casein (a major milk protein) and gliadin (a wheat-derived protein) releases peptides with opioid activity, and in the present study, we demonstrate that these food-derived proline-rich opioid peptides modulate cysteine uptake in cultured human neuronal and gastrointestinal (GI) epithelial cells via activation of opioid receptors. Decreases in cysteine uptake were associated with changes in the intracellular antioxidant glutathione and the methyl donor S-adenosylmethionine. Bovine and human casein-derived opioid peptides increased genome-wide DNA methylation in the transcription start site region with a potency order similar to their inhibition of cysteine uptake. Altered expression of genes involved in redox and methylation homeostasis was also observed. These results illustrate the potential of milk- and wheat-derived peptides to exert antioxidant and epigenetic changes which may be particularly important during the postnatal transition from placental to GI nutrition. Differences between peptides derived from human and bovine milk may contribute to developmental differences between breastfed and formula-fed infants. Restricted antioxidant capacity, caused by wheat- and milk-derived opioid peptides, may predispose susceptible individuals to inflammation and systemic oxidation, partly explaining the benefits of gluten-free or casein-free diets.

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Section: Discussionmentioning

confidence: 99%

Food-derived opioid peptides inhibit cysteine uptake with redox and epigenetic consequences

Trivedi

Shah

Al-Mughairy

et al. 2014

The Journal of Nutritional Biochemistry

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“…The proteins, gluten and casein, are hydrolyzed in the GI tract into hundreds to thousands of peptides, some of which have been shown to have opioid-like properties and are referred to as exorphins (Boutrou et al, 2013; Dohan, 1988a; Dohan, 1979, 1980, 1988b; Prandi et al, 2014; Reichelt, 1991, 1994; Reichelt et al, 1985; Reichelt et al, 1981; Reichelt et al, 1995; Reichelt et al, 2012). The immunomodulatory potential of these exorphins is not well-understood, with observations that among the repertoire of digested peptides, some have pro-inflammatory and others have anti-inflammatory effects (Aihara et al, 2014; Barnett et al, 2014; Haq et al, 2014; Kaminski et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

IgG dynamics of dietary antigens point to cerebrospinal fluid barrier or flow dysfunction in first-episode schizophrenia

Severance¹,

Gressitt²,

Alaedini³

et al. 2015

Brain, Behavior, and Immunity

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Schizophrenia is a complex brain disorder that may be accompanied by idiopathic inflammation. Classic central nervous system (CNS) inflammatory disorders such as viral encephalitis or multiple sclerosis can be characterized by incongruent serum and cerebrospinal fluid (CSF) IgG due in part to localized intrathecal synthesis of antibodies. The dietary antigens, wheat gluten and bovine milk casein, can induce a humoral immune response in susceptible individuals with schizophrenia, but the correlation between the food-derived serological and intrathecal IgG response is not known. Here, we measured IgG to wheat gluten and bovine milk casein in matched serum and CSF samples from 105 individuals with first-episode schizophrenia (n=75 antipsychotic-naïve), and 61 controls. We found striking correlations in the levels of IgG response to dietary proteins between serum and CSF of schizophrenia patients, but not controls (schizophrenia, R2=0.34–0.55, p≤0.0001; controls R2=0.05–0.06, p>0.33). A gauge of blood-CSF barrier permeability and CSF flow rate, the CSF-to-serum albumin ratio, was significantly elevated in cases compared to controls (p≤0.001–0.003). Indicators of intrathecal IgG production, the CSF IgG index and the specific Antibody Index, were not significantly altered in schizophrenia compared to controls. Thus, the selective diffusion of bovine milk casein and wheat gluten antibodies between serum and CSF in schizophrenia may be the function of a low-level anatomical barrier dysfunction or altered CSF flow rate, which may be transient in nature.

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“…The children have a restricted number of interests 1,2,3 . According to the American Psychiatric Association (1994), autism is associated with behavioral, developmental, neuropathological and sensory abnormalities.…”

Section: Introductionmentioning

confidence: 99%