Immuneneuroendocrine network (INEN) is defined as the interactions between immune, nervous, and endocrine systems. It is well accepted that immune responses can affect the functions of the endocrine and nervous systems. Remarkably, spore-making anaerobes and microaerophilic bacteria mainly from Clostridial species have been demonstrated to be elevated in autistic patients. Clostridia are resistant to most antibiotics used for frequent infections and are a reason of major hospital-acquired infectious disease. Clostridial species are the main gut colonist in primary life and are producers of PPA and other short-chain fatty acids. PPA-treated rats have typical autistic features, including hyperlocomotion, impaired social interaction, anxiety, and repetitive behavior. Because PPA is a weak organic acid and exists in ionized and non-ionized shapes at physiological pH, it easily crosses the gut-blood and blood-brain barriers and reaches the brain.
PPA is formed by bacteria in the intestinal tract and oral mucosa. Propionic acid (PPA) is an intermediate breakdown product of cellular fatty acids, and it is produced in the gut, along with other short-chain fatty acids such as acetate and butyrate, all of which are major metabolic products of enteric bacteria and are also fermentation products of nutritional carbohydrates and amino acids. Īnimal models of autism are being developed to examine the essential mechanisms, advance medicine, and identify approaches of the evaluation of symptoms of this disorder. Evidence of neuroinflammation in autism includes astrocyte and microglial activation, exclusively increased proinflammatory cytokines. However, further studies are needed to investigate the clinical benefits of prebiotics-rich diet in neurodevelopmental disorders, such as autism.īrain pathology in autism as a neurodevelopmental disorder is related to neuroinflammation in different brain parts. Our findings indicate that both bee pollen and propolis protect against neuroinflammation in the rodent model of autism. Both bee pollen and propolis were effective in ameliorating the neurotoxic effects of PPA demonstrating non-significant changes of IL-6 and IL-10 when compared to control healthy hamsters. The neurotoxic effects of PPA was clearly presented as much higher IL-6, as pro-inflammatory cytokine ( P<0.05), concomitant with much lower IL-10, as anti-inflammatory cytokine( P<0.015) compared to controls. Neuroinflammatory responses were evaluated using the levels of interferon γ (IFN-γ), interleukin 1 alpha (IL-1α), IL-6, IL-10, IL-12 (p70), vascular endothelial growth factor (VEGF), and tumor necrosis factor α (TNFα). Hamsters were classified as four groups: Group I, control Group II, autistic model/animals treated with 250 mg propionic acid (PPA)/kg body weight (BW)/day for 3 days Group III, animals treated with bee pollen at a dose of 250 mg/kg BW/day for 4 weeks and Group IV, animals treated with propolis at a dose of 250 mg/kg BW/day for 4 weeks. The study aimed to investigate the role of bee pollen and propolis in ameliorating neuroinflammation, including cytokine levels, in an animal model of autism. Prebiotics-rich diet maintains the healthy gut microbiota and hence can regulate the neuroinflammation indirectly. Neuroinflammation plays a major role in the pathogenesis of autism because the cytokine levels are typically disturbed in the brain in autistic patients.
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