{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T23:55:24Z","timestamp":1781567724320,"version":"3.54.5"},"reference-count":55,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,3,29]],"date-time":"2023-03-29T00:00:00Z","timestamp":1680048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Researchers Supporting Project, King Saud University","award":["RSP-2023R460"],"award-info":[{"award-number":["RSP-2023R460"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Autism spectrum disorder (ASD) is a progressively prevalent neurodevelopmental disorder with substantial clinical heterogeneity. Despite the considerable interest in dietary interventions, no consensus has been reached regarding the optimal nutritional therapy. The present study aimed to investigate the possible positive effect of goat\u2019s milk (GM) compared to cow\u2019s milk (CM) on ASD autistic features in a valproic acid (VPA; 600 mg\/kg)-induced white albino rat model of autism. All tests were conducted on rats that were divided into four groups (n = 15\/group): control with goat milk (GM) treatment, control with cow milk (CM) treatment, autistic with goat milk (GM) treatment, and autistic with cow milk treatment. The casein levels were also measured in GM and CM. Social behavior was assessed by three-chambered sociability to test social interaction after the intervention. After 15 days of intervention, selected biomarkers, such as glutathione (GSH), thiobarbituric acid reactive substance (TBARS), interleukin-6 (IL-6), neurotransmitter dopamine (DA), serotonin (5-hydroxytryptamine, 5-HT), and glutamate (GLU), were measured in blood serum and brain homogenates. The results showed a significant positive effect on social interaction in the VPA rat ASD model fed GM. Blood serum and brain samples showed a positive increase in TBARS in the VPA rat model fed GM, but brain and serum serotonin levels were lower in both VPA-GM and VPA-CM groups. Dopamine in serum was also lower in the VPA-CM group than in the VPA-GM group. IL-6 levels were slightly lower in the VPA-GM group than in the VPA-CM group. In comparison with cow\u2019s milk, goat\u2019s milk was effective in ameliorating the neurotoxic effects of VPA. Goat\u2019s milk may be considered a suitable source of dairy for children diagnosed with ASD. Autistic children with allergies to cow\u2019s milk could possibly convert to goat\u2019s milk. Nevertheless, more in-depth studies and clinical trials are recommended.<\/jats:p>","DOI":"10.3390\/metabo13040497","type":"journal-article","created":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T02:23:46Z","timestamp":1680143026000},"page":"497","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Potency of Goat Milk in Reducing the Induced Neurotoxic Effects of Valproic Acid in Rat Pups as a Rodent Model of Autism Spectrum Disorder"],"prefix":"10.3390","volume":"13","author":[{"given":"Alhanouf Mohammed","family":"Al-dossari","sequence":"first","affiliation":[{"name":"Department of Food Science and Nutrition, College of Food Science and Agriculture, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0778-922X","authenticated-orcid":false,"given":"Laila Naif","family":"Al-Harbi","sequence":"additional","affiliation":[{"name":"Department of Food Science and Nutrition, College of Food Science and Agriculture, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norah M.","family":"Al-Otaibi","sequence":"additional","affiliation":[{"name":"Antimicrobial Resistance Division, Reference Laboratory for Microbiology, Executive Department of Reference Laboratories, Research and Laboratories Sector, Saudi Food and Drug Authority (SFDA), Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah","family":"Almubarak","sequence":"additional","affiliation":[{"name":"Research Assistant, Veterinarian, Experimental Surgery and Animal Lab, Riyadh 12372, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed Tayseer","family":"Almnaizel","sequence":"additional","affiliation":[{"name":"Experimental Surgery and Animal Lab, College of Medicine, King Saud University, Riyadh 12372, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2043-1209","authenticated-orcid":false,"given":"Ghedeir M.","family":"Alshammari","sequence":"additional","affiliation":[{"name":"Department of Food Science and Nutrition, College of Food Science and Agriculture, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghalia","family":"Shamlan","sequence":"additional","affiliation":[{"name":"Department of Food Science and Nutrition, College of Food Science and Agriculture, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali A.","family":"Alshatwi","sequence":"additional","affiliation":[{"name":"Department of Food Science and Nutrition, College of Food Science and Agriculture, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afaf","family":"El-Ansary","sequence":"additional","affiliation":[{"name":"Central Research Laboratory, Female Center for Medical Studies and Scientific Section, King Saud University, Riyadh 11495, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.expneurol.2017.04.017","article-title":"The valproic acid-induced rodent model of autism","volume":"299","author":"Nicolini","year":"2018","journal-title":"Expermental Neurol."},{"key":"ref_2","first-page":"479364","article-title":"Molecular and therapeutic potential and toxicity of valproic acid","volume":"2010","author":"Morceau","year":"2010","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s00213-010-2010-9","article-title":"Maternal separation as a model of brain-gut axis dysfunction. Psychopharmacology","volume":"214","author":"Hyland","year":"2011","journal-title":"Psychopharmacology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3104","DOI":"10.1039\/D0FO02950E","article-title":"Goat and cow milk differ in altering microbiota composition and fermentation products in rats with gut dysbiosis induced by amoxicillin","volume":"12","author":"Butts","year":"2021","journal-title":"Food Funct."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1159\/000452818","article-title":"Human milk oligosaccharides influence neonatal mucosal and systemic immunity","volume":"69","author":"Donovan","year":"2016","journal-title":"Ann. Nutr. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1136\/gutjnl-2014-307544","article-title":"The human milk oligosaccharide 20-fucosyllactose modulates cd14 expression in human enterocytes, thereby attenuating lps-induced inflammation","volume":"65","author":"He","year":"2016","journal-title":"Gut"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s00394-008-3003-x","article-title":"The influence of children\u2019s diet on their cognition and behavior","volume":"47","author":"Benton","year":"2008","journal-title":"Eur. J. Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.bbi.2015.06.025","article-title":"The prebiotics 30 sialyllactose and 6 0 sialyllactose diminish stressor-induced anxiety-like behavior and colonic microbiota alterations: Evidence for effects on the gut-brain axis","volume":"50","author":"Tarr","year":"2015","journal-title":"Brain Behav. Immun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1517\/14728222.6.2.175","article-title":"Biochemical aspects in autism spectrum disorders: Updating the opioid-excess theory and presenting new opportunities for biomedical intervention","volume":"6","author":"Whiteley","year":"2002","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_10","first-page":"11","article-title":"Sialic acid in human milk: Composition and functions","volume":"42","author":"Nakano","year":"2001","journal-title":"Acta Paediatr. Taiwanica"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1093\/nutrit\/nuu016","article-title":"Impact of human milk bacteria and oligosaccharides on neonatal gut microbiota establishment and gut health","volume":"73","author":"Jost","year":"2015","journal-title":"Nutr. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Bienenstock, J., Buck, R.H., Linke, H., Forsythe, P., Stanisz, A.M., and Kunze, W.A. (2013). Fucosylated but not sialylated milk oligosaccharides diminish colon motor contractions. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0076236"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.idairyj.2015.10.006","article-title":"Effect of digestive enzymes on the bioactive properties of goat milk protein hydrolysates","volume":"54","author":"Guadix","year":"2016","journal-title":"Int. Dairy J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2771","DOI":"10.1271\/bbb.60267","article-title":"Comparison between Holstein cow\u2019s milk and Japanese-Saanen goat\u2019s milk in fatty acid composition, lipid digestibility and protein profile","volume":"70","author":"Tomotake","year":"2006","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2881","DOI":"10.1007\/s12161-017-0852-z","article-title":"Quantification of fatty acids in human, cow, buffalo, goat, yak, and camel milk using an improved one-step GC-FID method","volume":"10","author":"Teng","year":"2017","journal-title":"Food Anal. Methods"},{"key":"ref_16","first-page":"13","article-title":"Gluten and Casein: Their Roles in Psychiatric Disorders","volume":"3","year":"2022","journal-title":"J. Exp. Basic Med. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"292","DOI":"10.5152\/eurasianjmed.2020.19230","article-title":"Gluten-Free Casein-Free Diet for Autism Spectrum Disorders: Can It Be Effective in Solving Behavioural and Gastrointestinal Problems?","volume":"52","author":"Baspinar","year":"2020","journal-title":"Eurasian J. Med."},{"key":"ref_18","first-page":"113","article-title":"Quantitative analysis of casein precipitation from the various milk samples","volume":"9","author":"Kumaresan","year":"2017","journal-title":"J. Chem. Pharm. Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Al-Askar, M., Bhat, R.S., Selim, M., Al-Ayadhi, L., and El-Ansary, A. (2017). Postnatal treatment using curcumin supplements to amend the damage in VPA-induced rodent models of autism. BMC Complement. Altern. Med., 17.","DOI":"10.1186\/s12906-017-1763-7"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2058738418785514","DOI":"10.1177\/2058738418785514","article-title":"Leptin and camel milk abate oxidative stress status, genotoxicity induced in valproic acid rat model of autism","volume":"32","author":"Hamzawy","year":"2018","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1111\/j.1601-1848.2004.00076.x","article-title":"Sociability and preference for social novelty in five inbred strains: An approach to assess autistic-like behavior in mice","volume":"3","author":"Moy","year":"2004","journal-title":"Genes Brain Behav."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1134\/S2079978017010010","article-title":"Determination of proteins in blood. Part 1: Determination of total protein and albumin","volume":"7","author":"Buzanovskii","year":"2017","journal-title":"Rev. J. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.foodchem.2017.10.028","article-title":"Gastric digestion of cow and goat milk: Impact of infant and young child in vitro digestion conditions","volume":"245","author":"Hodgkinson","year":"2018","journal-title":"Food Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6484","DOI":"10.1039\/D2FO01136K","article-title":"Cow\u2019s milk \u03b1S1-casein is more sensitizing than goat\u2019s milk \u03b1S1-casein in a mouse model","volume":"13","author":"Zhang","year":"2022","journal-title":"Food Funct."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.smallrumres.2003.08.010","article-title":"Goat milk in human nutrition","volume":"51","author":"Haenlein","year":"2004","journal-title":"Small Rumin. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s13570-019-0138-8","article-title":"Comparative fatty-acid profile and atherogenicity index of milk from free grazing Nguni, Boer and non-descript goats in South Africa","volume":"9","author":"Idamokoro","year":"2019","journal-title":"Pastoralism"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1007\/s12031-018-1186-z","article-title":"The Independent and Combined Effects of Omega-3 and Vitamin B12 in Ameliorating Propionic Acid Induced Biochemical Features in Juvenile Rats as Rodent Model of Autism","volume":"66","author":"Alfawaz","year":"2018","journal-title":"J. Mol. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"107477","DOI":"10.1016\/j.neuropharm.2018.12.024","article-title":"Prenatal valproate in rodents as a tool to understand the neural underpinnings of social dysfunctions in autism spectrum disorder","volume":"159","author":"Tartaglione","year":"2019","journal-title":"Neuropharmacology"},{"key":"ref_29","first-page":"624","article-title":"The laboratory rat: Relating its age with human\u2019s","volume":"4","author":"Sengupta","year":"2013","journal-title":"Int. J. Prev. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1159\/000509109","article-title":"A systematic review of the valproic-acid-induced rodent model of autism","volume":"42","author":"Chaliha","year":"2020","journal-title":"Dev. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"338","DOI":"10.9758\/cpn.2016.14.4.338","article-title":"Valproic acid exposure during early postnatal gliogenesis leads to autistic-like behaviors in rats","volume":"14","author":"Mony","year":"2016","journal-title":"Clin. Psychopharmacol. Neurosci."},{"key":"ref_32","first-page":"261","article-title":"The influence of goat milk and soybean milk kefir on IL-6 and crp levels in diabetic rats","volume":"22","author":"Sunarti","year":"2015","journal-title":"Rom. J. Diabetes Nutr. Metab. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/s12640-012-9354-3","article-title":"Excitotoxicity in the pathogenesis of autism","volume":"23","author":"Essa","year":"2013","journal-title":"Neurotox. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"700968","DOI":"10.3389\/fncir.2021.700968","article-title":"Dopaminergic Dysregulation in Syndromic Autism Spectrum Disorders: Insights From Genetic Mouse Models","volume":"15","author":"Kosillo","year":"2021","journal-title":"Front. Neural Circuits"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1146\/annurev-neuro-102320-102847","article-title":"Oxytocin, neural plasticity, and social behavior","volume":"44","author":"Froemke","year":"2021","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.phrs.2018.07.010","article-title":"Extreme enhancement or depletion of serotonin transporter function and serotonin availability in autism spectrum disorder","volume":"140","author":"Garbarino","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.3389\/fnins.2021.682054","article-title":"Social Deficits and Repetitive Behaviors Are Improved by Early Postnatal Low-Dose VPA Intervention in a Novel shank3-Deficient Zebrafish Model","volume":"15","author":"Liu","year":"2021","journal-title":"Front. Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Alghamdi, M., Al-Ayadhi, L., Hassan, W.M., Bhat, R.S., Alonazi, M.A., and El-Ansary, A. (2022). Bee Pollen and Probiotics May Alter Brain Neuropeptide Levels in a Rodent Model of Autism Spectrum Disorders. Metabolites, 12.","DOI":"10.3390\/metabo12060562"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s40291-019-00430-0","article-title":"The role of lipidomics in autism spectrum disorder","volume":"24","author":"Chirumbolo","year":"2020","journal-title":"Mol. Diagn. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Moreno-Fern\u00e1ndez, J., L\u00f3pez-Aliaga, I., Garc\u00eda-Burgos, M., Alf\u00e9rez, J.M., and D\u00edaz-Castro, J. (2019). Fermented goat milk consumption enhances brain molecular functions during Iron deficiency anemia recovery. Nutrients, 11.","DOI":"10.3390\/nu11102394"},{"key":"ref_41","first-page":"31","article-title":"Dietary omega-3 fatty acids and psychiatry: Mood, behaviour, stress, depression, dementia and aging","volume":"9","author":"Bourre","year":"2005","journal-title":"J. Nutr. Health Aging"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.brainres.2007.10.063","article-title":"Further studies in the developmental hyperserotonemia model (DHS) of autism: Social, behavioral and peptide changes","volume":"1189","author":"McNamara","year":"2008","journal-title":"Brain Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.ijdevneu.2004.05.004","article-title":"Maternal administration of thalidomide or valproic acid causes abnormal serotonergic neurons in the offspring: Implication for pathogenesis of autism","volume":"23","author":"Miyazaki","year":"2005","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"418","DOI":"10.3389\/fnmol.2018.00418","article-title":"Glutamate, glutamine and GABA levels in rat brain measured using MRS, HPLC and NMR methods in study of two models of autism","volume":"11","author":"Zieminska","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"105437","DOI":"10.1016\/j.phrs.2021.105437","article-title":"The impact of glutathione metabolism in autism spectrum disorder","volume":"166","author":"Dos","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1186\/s12974-014-0189-0","article-title":"GABAergic\/glutamatergic imbalance relative to excessive neuroinflammation in autism spectrum disorders","volume":"11","year":"2014","journal-title":"J. Neuroinflamm."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"25","DOI":"10.5214\/ans.0972.7531.260106","article-title":"Negative geotaxis: An early age behavioral hallmark to VPA rat model of autism","volume":"26","author":"Ruhela","year":"2019","journal-title":"Ann. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1179\/1476830514Y.0000000110","article-title":"Are \u2018leaky gut\u2019and behavior associated with gluten and dairy containing diet in children with autism spectrum disorders?","volume":"18","author":"Navarro","year":"2015","journal-title":"Nutr. Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/s41579-020-00460-0","article-title":"The Gut Microbiota-Brain axis in Behaviour and Brain Disorders","volume":"19","author":"Morais","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Srikantha, P., and Mohajeri, M.H. (2019). The possible role of the microbiota-gut-brain-axis in autism spectrum disorder. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20092115"},{"key":"ref_51","first-page":"602834","article-title":"Camel milk as a potential therapy as an antioxidant in autism spectrum disorder (ASD)","volume":"2013","author":"Elamin","year":"2013","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.jpsychires.2020.06.032","article-title":"Gut microbiota changes in patients with autism spectrum disorders","volume":"129","author":"Ding","year":"2020","journal-title":"J. Psychiatr. Res."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Abuaish, S., Al-Otaibi, N., Abujamel, T., Alzahrani, S., Alotaibi, S., AlShawakir, Y., Aabed, K., and El-Ansary, A. (2021). Fecal Transplant and Bifidobacterium Treatments Modulate Gut Clostridium Bacteria and Rescue Social Impairment and Hippocampal BDNF Expression in a Rodent Model of Autism. Brain Sci., 11.","DOI":"10.3390\/brainsci11081038"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/s41586-022-04396-8","article-title":"A gut-derived metabolite alters brain activity and anxiety behaviour in mice","volume":"607","author":"Needham","year":"2022","journal-title":"Nature"},{"key":"ref_55","unstructured":"Chau, K.F. (2017). The Effect of Sulforaphane on Valproic Acid on Mice Model of Autism. [Ph.D. Thesis, Chinese University of Hong Kong]."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/13\/4\/497\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:06:23Z","timestamp":1760123183000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/13\/4\/497"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,29]]},"references-count":55,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["metabo13040497"],"URL":"https:\/\/doi.org\/10.3390\/metabo13040497","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,29]]}}}