1. Findings in normal rats following administration of gliadorphin-7 (GD-7)
Zhongjie Sun, Robert Cade Peptides. 2003 Feb;24(2):321-3. doi: 10.1016/s0196-9781(03)00043-3.
This paper discusses the effects of gliadorphin-7 (GD-7) infusion in rats and contrasts them with those of beta-casomorphin-7 (betaC-7). Both induce FLI in a dose related fashion. Very strong expression in both geniculate nuclei (GN) and the alveus hippocampus follow GD-7 400 microgram and betaC-7 30 microgram/kg BW. GD-7 affects only these three regions while betaC-7affects 45. FLI is prevented by Naloxone 2mg/kg BW in all regions except the GN where it is diminished 60%. betaC-7 causes bizarre behavior beginning 60s after infusion is started. GD-7 causes no behavioral change. These findings suggest GD-7 gains access to brain cells by diffusion through circumventricular organs while betaC-7 passes the BBB by carrier facilitation.
2. Behavioral effects of food-derived opioid-like peptides in rodents: Implications for schizophrenia?
Josh Lister, Paul J Fletcher, José N Nobrega, Gary Remington Pharmacol Biochem Behav. 2015 Jul;134:70-8. doi: 10.1016/j.pbb.2015.01.020. Epub 2015 Feb 7.
Dohan proposed that an overload of dietary peptides, such as those derived from wheat gluten and milk casein, could be a factor relevant to the development or maintenance of schizophrenia (SZ) symptoms in at least a subset of vulnerable individuals. Rodent behavioral models may offer insight into the plausibility of Dohan's exorphin hypothesis by providing a means to directly study the effects of such peptides. Accordingly, a review of the literature on the behavioral effects of food-derived opioid-like peptides in rodents was undertaken. Studies using a variety of behavioral tests to examine the effects of several classes of food-derived opioid-like peptides were identified and reviewed. Peptides derived from casein (β-casomorphins; BCMs, n=19), spinach (rubiscolins; RCs, n=4), and soy (soymorphins; SMs, n=1) were behaviorally active in various paradigms assessing nociception, spontaneous behavior, and memory. Surprisingly, only a single study evaluating a gluten-derived peptide (gliadorphin-7; GD-7, n=1) was identified and included in this review. In conclusion, food-derived peptides can affect rodent behavior, but more studies of GDs using diverse behavioral batteries are warranted. Assuming they occur in sufficient quantities during protein digestion and can access central opioid receptors (which entails crossing both the gastrointestinal and blood-brain barriers intact), these peptides may affect human behavior. Although BCMs and GDs may not be directly pathogenic in SZ, documented associations of casein and gluten sensitivity with SZ justify increased patient screening and dietary intervention where necessary.
3. Degradation of food-derived opioid peptides by bifidobacteria
T Sakurai, A Yamada, N Hashikura, T Odamaki, J-Z Xiao Benef Microbes. 2018 Jun 15;9(4):675-682. doi: 10.3920/BM2017.0165. Epub 2018 Apr 10.
Some food-derived opioid peptides have been reported to cause diseases, such as gastrointestinal inflammation, celiac disease, and mental disorders. Bifidobacterium is a major member of the dominant human gut microbiota, particularly in the gut of infants. In this study, we evaluated the potential of Bifidobacterium in the degradation of food-derived opioid peptides. All strains tested showed some level of dipeptidyl peptidase activity, which is thought to be involved in the degradation of food-derived opioid peptides. However, this activity was higher in bifidobacterial strains that are commonly found in the intestines of human infants, such as Bifidobacterium longum subsp. longum, B. longum subsp. infantis, Bifidobacterium breve and Bifidobacterium bifidum, than in those of other species, such as Bifidobacterium animalis and Bifidobacterium pseudolongum. In addition, some B. longum subsp. infantis and B. bifidum strains showed degradative activity in food-derived opioid peptides such as human and bovine milk-derived casomorphin-7 and wheat gluten-derived gliadorphin-7. A further screening of B. bifidum strains revealed some bifidobacterial strains that could degrade all three peptides. Our results revealed the potential of Bifidobacterium species in the degradation of food-derived opioid peptides, particularly for species commonly found in the intestine of infants. Selected strains of B. longum subsp. infantis and B. bifidum with high degradative capabilities can be used as probiotic microorganisms to eliminate food-derived opioid peptides and contribute to host health.