{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T12:50:39Z","timestamp":1763988639359,"version":"build-2065373602"},"reference-count":80,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Florida Legislative","award":["2014\u20132024"],"award-info":[{"award-number":["2014\u20132024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We previously demonstrated that propionic acid (PPA), a common food preservative and a metabolic byproduct of bacteria in dysbiosis (as seen in individuals affected with autism spectrum disorder, ASD), can lead to increased brain astrocyte proliferation and neuroinflammation in mice. We also showed that in vitro treatment of human neural stem cells with PPA increased glial cell vs. neuron differentiation and yielded a marked increase in pro-inflammatory cytokines. In this study, a group of mice (FVB\/N-Tg(GFAPGFP)14Mes\/J) was exposed in utero through the maternal diet and postnatally ad libitum to a PPA-rich diet, while the control group was fed a normal diet. Intestinal tissue from offspring mice at 1 month (1 M) and 5 months (5 M) were then studied for neurodifferentiation and gastrointestinal (GI) inflammation. There was a significant increase in GFAP (Glial fibrillary acidic protein) expression (1.5427-fold and 1.6097-fold in 1 M and 5 M, respectively) and GFAP protein levels (1.5616-fold and 1.6701-fold in 1 M and 5 M, respectively) in the PPA group mice. It is worth mentioning that the expression level of intestinal astrocyte markers in the PPA group was significantly and multi-fold lower than that in the brain tissue. Contrary to data from brain tissue, the expression of pro-inflammatory cytokines in the PPA group decreased in intestinal tissue at 5 M (IL-6: 0.4403-fold; TNF-\u03b1: 0.4007-fold), while IL-10 expression and protein levels increased (1.9360-fold and 1.3428-fold, respectively). The data demonstrates that although there was a significant increase in GFAP in the intestine suggesting gliosis, there was an overall anti-inflammatory cytokine profile. The effect of PPA on intestinal cytokines is most likely in part due to the lower expression of GFAP in the enteric nervous system than the central nervous system (and the lower number of intestinal glia than astrocytes in the brain) and the dominance of intestinal macrophages and other immune cells compared to that in the brain. The overall finding strongly suggests that the PPA-rich diet affects the enteric glia state as shown by an increase in GFAP; however, it maintains the overall anti-inflammatory cytokine profile, possibly due to M2 macrophage polarization.<\/jats:p>","DOI":"10.3390\/ijms26199295","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T15:54:54Z","timestamp":1758642894000},"page":"9295","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Maternal and Postnatal Ad Libitum Propionic Acid-Rich Diet in Mice Alters Intestinal Glia Proliferation and Inflammatory Response: Contrary to Effect in the Brain"],"prefix":"10.3390","volume":"26","author":[{"given":"Piotr P.","family":"Lagod","sequence":"first","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Latifa S.","family":"Abdelli","sequence":"additional","affiliation":[{"name":"Health Sciences Department, College of Health Professions and Sciences, University of Central Florida, Orlando, FL 32816, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9222-4527","authenticated-orcid":false,"given":"Saleh A.","family":"Naser","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Taniya, M.A., Chung, H.J., Al Mamun, A., Alam, S., Aziz, M.A., Emon, N.U., Islam, M.M., Hong, S.S., Podder, B.R., and Ara Mimi, A. (2022). Role of Gut Microbiome in Autism Spectrum Disorder and Its Therapeutic Regulation. Front. Cell. Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.915701"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Greenman, N., Abdelli, L.S., Hassouneh, S.A.-D., Ali, S., Johnston, C., Naser, S.A., and Azarian, T. (2024). Impact of propionic acid-rich diets on microbial composition of the murine gut microbiome. Front. Microbiomes, 3.","DOI":"10.3389\/frmbi.2024.1451735"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/s41392-022-00974-4","article-title":"Microbiota in health and diseases","volume":"7","author":"Hou","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1038\/nature06244","article-title":"The human microbiome project","volume":"449","author":"Turnbaugh","year":"2007","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/nm.4517","article-title":"Current understanding of the human microbiome","volume":"24","author":"Gilbert","year":"2018","journal-title":"Nat. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/J.ENG.2017.01.008","article-title":"The Human Microbiota in Health and Disease","volume":"3","author":"Wang","year":"2017","journal-title":"Engineering"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Afzaal, M., Saeed, F., Shah, Y.A., Hussain, M., Rabail, R., Socol, C.T., Hassoun, A., Pateiro, M., Lorenzo, J.M., and Rusu, A.V. (2022). Human gut microbiota in health and disease: Unveiling the relationship. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.999001"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1111\/lam.13333","article-title":"Gut\u2013organ axis: A microbial outreach and networking","volume":"72","author":"Ahlawat","year":"2021","journal-title":"Lett. Appl. Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Chen, Y., Xu, J., and Chen, Y. (2021). Regulation of Neurotransmitters by the Gut Microbiota and Effects on Cognition in Neurological Disorders. Nutrients, 13.","DOI":"10.3390\/nu13062099"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Wilkins, L.J., Monga, M., and Miller, A.W. (2019). Defining Dysbiosis for a Cluster of Chronic Diseases. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-49452-y"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e00478","DOI":"10.1016\/j.neurot.2024.e00478","article-title":"Gut microbiota dysbiosis and neurologic diseases: New Horizon with potential diagnostic and therapeutic impact","volume":"21","author":"Keshavarzian","year":"2024","journal-title":"Neurotherapeutics"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"9942","DOI":"10.3748\/wjg.v20.i29.9942","article-title":"Pathophysiology of autism spectrum disorders: Revisiting gastrointestinal involvement and immune imbalance","volume":"20","author":"Samsam","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S55","DOI":"10.21037\/tp.2019.09.09","article-title":"Autism spectrum disorder: Definition, epidemiology, causes, and clinical evaluation","volume":"9","author":"Hodges","year":"2020","journal-title":"Transl. Pediatr."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Lordan, R., Storni, C., and De Benedictis, C. (2021). Autism Spectrum Disorders: Diagnosis and Treatment, Exon Publications.","DOI":"10.36255\/exonpublications.autismspectrumdisorders.2021.diagnosis"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15585\/mmwr.ss7202a1","article-title":"Prevalence and Characteristics of Autism Spectrum Disorder Among Children Aged 8 Years\u2014Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2020","volume":"72","author":"Maenner","year":"2023","journal-title":"MMWR Surveill. Summ."},{"key":"ref_16","first-page":"Cd009260","article-title":"Early intensive behavioral intervention (EIBI) for young children with autism spectrum disorders (ASD)","volume":"10","author":"Reichow","year":"2012","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_17","unstructured":"Weitlauf, A.S., McPheeters, M.L., Peters, B., Sathe, N., Travis, R., Aiello, R., Williamson, E., Veenstra-VanderWeele, J., Krishnaswami, S., and Jerome, R. (2014). AHRQ Comparative Effectiveness Reviews, Therapies for Children with Autism Spectrum Disorder: Behavioral Interventions Update."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Lagod, P.P., and Naser, S.A. (2023). The Role of Short-Chain Fatty Acids and Altered Microbiota Composition in Autism Spectrum Disorder: A Comprehensive Literature Review. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242417432"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1111\/j.1365-2672.1991.tb02739.x","article-title":"The control and consequences of bacterial fermentation in the human colon","volume":"70","author":"Cummings","year":"1991","journal-title":"J. Appl. Bacteriol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1136\/gut.28.10.1221","article-title":"Short chain fatty acids in human large intestine, portal, hepatic and venous blood","volume":"28","author":"Cummings","year":"1987","journal-title":"Gut"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1111\/1462-2920.13589","article-title":"Formation of propionate and butyrate by the human colonic microbiota","volume":"19","author":"Louis","year":"2017","journal-title":"Environ. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Strati, F., Cavalieri, D., Albanese, D., De Felice, C., Donati, C., Hayek, J., Jousson, O., Leoncini, S., Renzi, D., and Calabr\u00f2, A. (2017). New evidences on the altered gut microbiota in autism spectrum disorders. Microbiome, 5.","DOI":"10.1186\/s40168-017-0242-1"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.anaerobe.2011.03.007","article-title":"State of the art; microbiology in health and disease. Intestinal bacterial flora in autism","volume":"17","author":"Finegold","year":"2011","journal-title":"Anaerobe"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.mehy.2011.04.032","article-title":"Desulfovibrio species are potentially important in regressive autism","volume":"77","author":"Finegold","year":"2011","journal-title":"Med. Hypotheses"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Li, Q., Han, Y., Dy, A.B.C., and Hagerman, R.J. (2017). The Gut Microbiota and Autism Spectrum Disorders. Front. Cell. Neurosci., 11.","DOI":"10.3389\/fncel.2017.00120"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/msystems.00193-20","article-title":"Children with Autism and Their Typically Developing Siblings Differ in Amplicon Sequence Variants and Predicted Functions of Stool-Associated Microbes","volume":"6","author":"David","year":"2021","journal-title":"Msystems"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1007\/s10545-017-0070-2","article-title":"Autism spectrum disorders in propionic acidemia patients","volume":"41","author":"Barbier","year":"2018","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"He, J., Gong, X., Hu, B., Lin, L., Lin, X., Gong, W., Zhang, B., Cao, M., Xu, Y., and Xia, R. (2023). Altered Gut Microbiota and Short-chain Fatty Acids in Chinese Children with Constipated Autism Spectrum Disorder. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-46566-2"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"De Angelis, M., Piccolo, M., Vannini, L., Siragusa, S., De Giacomo, A., Serrazzanetti, D.I., Cristofori, F., Guerzoni, M.E., Gobbetti, M., and Francavilla, R. (2013). Fecal microbiota and metabolome of children with autism and pervasive developmental disorder not otherwise specified. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0076993"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) (2014). Scientific Opinion on the re-evaluation of propionic acid (E 280), sodium propionate (E 281), calcium propionate (E 282) and potassium propionate (E 283) as food additives. EFSA J., 12, 3779.","DOI":"10.2903\/j.efsa.2014.3779"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Rahman, M., Islam, R., Hasan, S., Zzaman, W., Rana, M.R., Ahmed, S., Roy, M., Sayem, A., Matin, A., and Raposo, A. (2022). A Comprehensive Review on Bio-Preservation of Bread: An Approach to Adopt Wholesome Strategies. Foods, 11.","DOI":"10.3390\/foods11030319"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.ymgme.2016.10.009","article-title":"Autism in patients with propionic acidemia","volume":"119","author":"Witters","year":"2016","journal-title":"Mol. Genet. Metab."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Meeking, M.M., MacFabe, D.F., Mepham, J.R., Foley, K.A., Tichenoff, L.J., Boon, F.H., Kavaliers, M., and Ossenkopp, K.P. (2020). Propionic acid induced behavioural effects of relevance to autism spectrum disorder evaluated in the hole board test with rats. Prog. Neuropsychopharmacol. Biol. Psychiatry, 97.","DOI":"10.1016\/j.pnpbp.2019.109794"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/j.neuropharm.2008.01.013","article-title":"Intracerebroventricular injection of propionic acid, an enteric bacterial metabolic end-product, impairs social behavior in the rat: Implications for an animal model of autism","volume":"54","author":"Shultz","year":"2008","journal-title":"Neuropharmacology"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Foley, K.A., Ossenkopp, K.P., Kavaliers, M., and Macfabe, D.F. (2014). Pre- and neonatal exposure to lipopolysaccharide or the enteric metabolite, propionic acid, alters development and behavior in adolescent rats in a sexually dimorphic manner. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087072"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1002\/jdn.10011","article-title":"Behavioural and brain ultrastructural changes following the systemic administration of propionic acid in adolescent male rats. Further development of a rodent model of autism","volume":"80","author":"Lobzhanidze","year":"2020","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1542\/peds.2013-3995","article-title":"Gastrointestinal symptoms in autism spectrum disorder: A meta-analysis","volume":"133","author":"McElhanon","year":"2014","journal-title":"Pediatrics"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"153","DOI":"10.2147\/PHMT.S85717","article-title":"Gastrointestinal symptoms and autism spectrum disorder: Links and risks\u2014a possible new overlap syndrome","volume":"6","author":"Wasilewska","year":"2015","journal-title":"Pediatr. Health Med. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1038\/s41575-023-00857-1","article-title":"Autism spectrum disorders and the gastrointestinal tract: Insights into mechanisms and clinical relevance","volume":"21","author":"Hung","year":"2024","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/nrgastro.2016.107","article-title":"The bowel and beyond: The enteric nervous system in neurological disorders","volume":"13","author":"Rao","year":"2016","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1007\/s11894-010-0129-9","article-title":"Enteric nervous system in the small intestine: Pathophysiology and clinical implications","volume":"12","author":"Nezami","year":"2010","journal-title":"Curr. Gastroenterol. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"8024171","DOI":"10.1155\/2020\/8024171","article-title":"The Enteric Nervous System and Its Emerging Role as a Therapeutic Target","volume":"2020","author":"Fleming","year":"2020","journal-title":"Gastroenterol. Res. Pract."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Santhosh, S., Zanoletti, L., Stamp, L.A., Hao, M.M., and Matteoli, G. (2024). From diversity to disease: Unravelling the role of enteric glial cells. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1408744"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1152\/physrev.00018.2022","article-title":"The enteric nervous system","volume":"103","author":"Sharkey","year":"2023","journal-title":"Physiol. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1002\/ar.24128","article-title":"Enteric Glia: S100, GFAP, and Beyond","volume":"302","author":"Grundmann","year":"2019","journal-title":"Anat. Rec."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Wang, X., Tang, R., Wei, Z., Zhan, Y., Lu, J., and Li, Z. (2023). The enteric nervous system deficits in autism spectrum disorder. Front. Neurosci., 17.","DOI":"10.3389\/fnins.2023.1101071"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4099","DOI":"10.1113\/JP271919","article-title":"Insights into the mechanisms underlying colonic motor patterns","volume":"594","author":"Spencer","year":"2016","journal-title":"J. Physiol."},{"key":"ref_48","unstructured":"Lyte, M., and Cryan, J.F. (2014). The Enteric Nervous System and Gastrointestinal Innervation: Integrated Local and Central Control. Microbial Endocrinology: The Microbiota-Gut-Brain Axis in Health and Disease, Springer."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.ijdevneu.2017.01.004","article-title":"Serum levels of Glial fibrillary acidic protein in Chinese children with autism spectrum disorders","volume":"57","author":"Wang","year":"2017","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1080\/14734220500208846","article-title":"Glial fibrillary acidic protein is elevated in superior frontal, parietal and cerebellar cortices of autistic subjects","volume":"4","author":"Laurence","year":"2005","journal-title":"Cerebellum"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Simone, M., De Giacomo, A., Palumbi, R., Palazzo, C., Lucisano, G., Pompamea, F., Micella, S., Pascali, M., Gabellone, A., and Marzulli, L. (2023). Serum Neurofilament Light Chain and Glial Fibrillary Acidic Protein as Potential Diagnostic Biomarkers in Autism Spectrum Disorders: A Preliminary Study. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24033057"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/s41586-021-04006-z","article-title":"Regulation of intestinal immunity and tissue repair by enteric glia","volume":"599","author":"Progatzky","year":"2021","journal-title":"Nature"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1002\/aur.2656","article-title":"Association between autism spectrum disorder and inflammatory bowel disease: A systematic review and meta-analysis","volume":"15","author":"Kim","year":"2022","journal-title":"Autism Res."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Hou, Q., Huang, J., Ayansola, H., Masatoshi, H., and Zhang, B. (2021). Intestinal Stem Cells and Immune Cell Relationships: Potential Therapeutic Targets for Inflammatory Bowel Diseases. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.623691"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Abdelli, L.S., Samsam, A., and Naser, S.A. (2019). Propionic Acid Induces Gliosis and Neuro-inflammation through Modulation of PTEN\/AKT Pathway in Autism Spectrum Disorder. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-45348-z"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Lagod, P.P., Abdelli, L.S., and Naser, S.A. (2024). An In Vivo Model of Propionic Acid-Rich Diet-Induced Gliosis and Neuro-Inflammation in Mice (FVB\/N-Tg(GFAPGFP)14Mes\/J): A Potential Link to Autism Spectrum Disorder. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25158093"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Hughes, H.K., Onore, C.E., Careaga, M., Rogers, S.J., and Ashwood, P. (2022). Increased Monocyte Production of IL-6 after Toll-like Receptor Activation in Children with Autism Spectrum Disorder (ASD) Is Associated with Repetitive and Restricted Behaviors. Brain Sci., 12.","DOI":"10.3390\/brainsci12020220"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Fattorusso, A., Di Genova, L., Dell\u2019Isola, G.B., Mencaroni, E., and Esposito, S. (2019). Autism Spectrum Disorders and the Gut Microbiota. Nutrients, 11.","DOI":"10.3390\/nu11030521"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.jtcme.2022.03.001","article-title":"Gut microbiota and Autism Spectrum Disorder: From pathogenesis to potential therapeutic perspectives","volume":"13","author":"Mehra","year":"2022","journal-title":"J. Tradit. Complement. Med."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Ashwood, P. (2023). Preliminary Findings of Elevated Inflammatory Plasma Cytokines in Children with Autism Who Have Co-Morbid Gastrointestinal Symptoms. Biomedicines, 11.","DOI":"10.3390\/biomedicines11020436"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15585\/mmwr.ss7011a1","article-title":"Prevalence and Characteristics of Autism Spectrum Disorder Among Children Aged 8 Years\u2014Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2018","volume":"70","author":"Maenner","year":"2021","journal-title":"MMWR Surveill. Summ."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.neubiorev.2021.07.023","article-title":"Neuroinflammation in autism spectrum disorders: Exercise as a \u201cpharmacological\u201d tool","volume":"129","author":"Toscano","year":"2021","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Than, U.T.T., Nguyen, L.T., Nguyen, P.H., Nguyen, X.-H., Trinh, D.P., Hoang, D.H., Nguyen, P.A.T., and Dang, V.D. (2023). Inflammatory mediators drive neuroinflammation in autism spectrum disorder and cerebral palsy. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-49902-8"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e199","DOI":"10.1038\/tp.2012.120","article-title":"Evidence for sustained elevation of IL-6 in the CNS as a key contributor of depressive-like phenotypes","volume":"2","author":"Neal","year":"2012","journal-title":"Transl. Psychiatry"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.bbr.2006.07.025","article-title":"Neurobiological effects of intraventricular propionic acid in rats: Possible role of short chain fatty acids on the pathogenesis and characteristics of autism spectrum disorders","volume":"176","author":"MacFabe","year":"2007","journal-title":"Behav. Brain Res."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Choi, J., Lee, S., Won, J., Jin, Y., Hong, Y., Hur, T.-Y., Kim, J.-H., Lee, S.-R., and Hong, Y. (2018). Pathophysiological and neurobehavioral characteristics of a propionic acid-mediated autism-like rat model. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0192925"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Alsubaiei, S.R.M., Alfawaz, H.A., Bhat, R.S., and El-Ansary, A. (2023). Nutritional Intervention as a Complementary Neuroprotective Approach against Propionic Acid-Induced Neurotoxicity and Associated Biochemical Autistic Features in Rat Pups. Metabolites, 13.","DOI":"10.3390\/metabo13060738"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Chen, X., Cheng, Q., and Zhang, G.F. (2025). Elevated propionate and its association with neurological dysfunctions in propionic acidemia. Front. Mol. Neurosci., 18.","DOI":"10.3389\/fnmol.2025.1499376"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Deng, W., Wang, S., Li, F., Wang, F., Xing, Y.P., Li, Y., Lv, Y., Ke, H., Li, Z., and Lv, P.J. (2022). Gastrointestinal symptoms have a minor impact on autism spectrum disorder and associations with gut microbiota and short-chain fatty acids. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.1000419"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Schneider, R., Leven, P., Mallesh, S., Bre\u00dfer, M., Schneider, L., Mazzotta, E., Fadda, P., Glowka, T., Vilz, T.O., and Lingohr, P. (2022). IL-1-dependent enteric gliosis guides intestinal inflammation and dysmotility and modulates macrophage function. Commun. Biol., 5.","DOI":"10.1038\/s42003-022-03772-4"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"14951","DOI":"10.1021\/acs.jafc.3c00278","article-title":"Propionic Acid Driven by the Lactobacillus johnsonii Culture Supernatant Alleviates Colitis by Inhibiting M1 Macrophage Polarization by Modulating the MAPK Pathway in Mice","volume":"71","author":"Wu","year":"2023","journal-title":"J. Agric. Food Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"102183","DOI":"10.1016\/j.coi.2022.102183","article-title":"The role of enteric glia in intestinal immunity","volume":"77","author":"Progatzky","year":"2022","journal-title":"Curr. Opin. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Yang, R., Hu, X., Xie, X., Chen, H., Fang, H., Zhu, L., and Li, Z. (2020). Propionic Acid Targets the TLR4\/NF-\u03baB Signaling Pathway and Inhibits LPS-Induced Intestinal Barrier Dysfunction: In Vitro and In Vivo Studies. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.573475"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1683347","DOI":"10.1080\/2162402X.2019.1683347","article-title":"The M2 macrophage marker CD206: A novel prognostic indicator for acute myeloid leukemia","volume":"9","author":"Xu","year":"2020","journal-title":"Oncoimmunology"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Liang, L., Song, D., Wu, K., Ouyang, Z., Huang, Q., Lei, G., Zhou, K., Xiao, J., and Wu, H. (2022). Sequential activation of M1 and M2 phenotypes in macrophages by Mg degradation from Ti-Mg alloy for enhanced osteogenesis. Biomater. Res., 26.","DOI":"10.1186\/s40824-022-00262-w"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Wright, P.B., McDonald, E., Bravo-Blas, A., Baer, H.M., Heawood, A., Bain, C.C., Mowat, A.M., Clay, S.L., Robertson, E.V., and Morton, F. (2021). The mannose receptor (CD206) identifies a population of colonic macrophages in health and inflammatory bowel disease. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-98611-7"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1046\/j.0022-202x.2001.01665.x","article-title":"Expression and function of the mannose receptor CD206 on epidermal dendritic cells in inflammatory skin diseases","volume":"118","author":"Wollenberg","year":"2002","journal-title":"J. Investig. Dermatol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Tanaka, S., Ohgidani, M., Hata, N., Inamine, S., Sagata, N., Shirouzu, N., Mukae, N., Suzuki, S.O., Hamasaki, H., and Hatae, R. (2021). CD206 Expression in Induced Microglia-Like Cells From Peripheral Blood as a Surrogate Biomarker for the Specific Immune Microenvironment of Neurosurgical Diseases Including Glioma. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.670131"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Xue, Q., Yan, Y., Zhang, R., and Xiong, H. (2018). Regulation of iNOS on Immune Cells and Its Role in Diseases. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19123805"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1016\/j.chom.2015.04.004","article-title":"Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life","volume":"17","author":"Roswall","year":"2015","journal-title":"Cell Host Microbe"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/19\/9295\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:48:08Z","timestamp":1760035688000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/19\/9295"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,23]]},"references-count":80,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["ijms26199295"],"URL":"https:\/\/doi.org\/10.3390\/ijms26199295","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,9,23]]}}}