An integrative exploration of environmental stressors on the microbiome-gut-brain axis and immune mechanisms promoting neurological disorders

References

• Adelman, M. W., M. H. Woodworth, C. Langelier, L. M. Busch, J. A. Kempker, C. S. Kraft, and G. S. Martin. 2020. “The Gut microbiome’s Role in the Development, Maintenance, and Outcomes of Sepsis.” Critical Care 24 (1): 278. https://doi.org/10.1186/s13054-020-02989-1.
   PubMed Web of Science ®Google Scholar
• Aghamohammad, S., A. Hafezi, and M. Rohani. 2023. “Probiotics As Functional Foods: How Probiotics Can Alleviate the Symptoms of Neurological Disabilities.” Biomedicine & Pharmacotherapy 163:114816. https://doi.org/10.1016/j.biopha.2023.114816.
   PubMedGoogle Scholar
• Agirman, G., K. B. Yu, and E. Y. Hsiao. 2021. “Signaling Inflammation Across the Gut-Brain Axis.” Science 374 (6571): 1087–1092. https://doi.org/10.1126/science.abi6087.
   PubMed Web of Science ®Google Scholar
• Aho, V. T. E., M. C. Houser, P. A. B. Pereira, J. Chang, K. Rudi, L. Paulin, V. Hertzberg, P. Auvinen, M. G. Tansey, and F. Scheperjans. 2021. “Relationships of Gut Microbiota, Short-Chain Fatty Acids, Inflammation, and the Gut Barrier in Parkinson’s Disease.” Molecular Neurodegeneration 16 (1): 6. https://doi.org/10.1186/s13024-021-00427-6.
   PubMed Web of Science ®Google Scholar
• Alamoudi, M. U., S. Hosie, A. E. Shindler, J. L. Wood, A. E. Franks, and E. L. Hill-Yardin. 2022. “Comparing the Gut Microbiome in Autism and Preclinical Models: A Systematic Review.” Frontiers in Cellular & Infection Microbiology 12:905841. https://doi.org/10.3389/fcimb.2022.905841.
   PubMedGoogle Scholar
• Alexaki, V. I. 2021. “The Impact of Obesity on Microglial Function: Immune, Metabolic and Endocrine Perspectives.” Cells 10 (7): 1584. https://doi.org/10.3390/cells10071584.
   PubMedGoogle Scholar
• Alharthi, A., S. Alhazmi, N. Alburae, and A. Bahieldin. 2022. “The Human Gut Microbiome As a Potential Factor in Autism Spectrum Disorder.” International Journal of Molecular Sciences 23 (3): 1363. https://doi.org/10.3390/ijms23031363.
   PubMedGoogle Scholar
• Almuqbil, M. A., S. E. Waisbren, H. L. Levy, and J. D. Picker. 2019. “Revising the Psychiatric Phenotype of Homocystinuria.” Genetics in Medicine 21 (8): 1827–1831. https://doi.org/10.1038/s41436-018-0419-4.
   PubMedGoogle Scholar
• Al-Sadeq, D. W., and G. K. Nasrallah. 2020. “The Spectrum of Mutations of Homocystinuria in the MENA Region.” Genes (Basel) 11 (3): 330. https://doi.org/10.3390/genes11030330.
   PubMedGoogle Scholar
• Anand, N., V. R. Gorantla, and S. B. Chidambaram. 2022. “The Role of Gut Dysbiosis in the Pathophysiology of Neuropsychiatric Disorders.” Cells 12 (1): 54. https://doi.org/10.3390/cells12010054.
   PubMed Web of Science ®Google Scholar
• Appel, L. J., E. R. Miller III, S. H. Jee, R. Stolzenberg-Solomon, P. H. Lin, M. R. Erlinger, T. Nadeau, J. Selhub, and J. Selhub. 2000. “Effect of Dietary Patterns on Serum Homocysteine: Results of a Randomized, Controlled Feeding Study.” Circulation 102 (8): 852–857. https://doi.org/10.1161/01.CIR.102.8.852.
   PubMed Web of Science ®Google Scholar
• Appleton, J. 2018. “The Gut-Brain Axis: Influence of Microbiota on Mood and Mental Health.” Integrative Medicine (Encinitas, California) 17 (4): 28–32.
   PubMedGoogle Scholar
• Arpaia, N., C. Campbell, X. Fan, S. Dikiy, J. van der Veeken, P. deRoos, H. Liu, et al. 2013. “Metabolites Produced by Commensal Bacteria Promote Peripheral Regulatory T-Cell Generation.” Nature 504 (7480): 451–455. https://doi.org/10.1038/nature12726.
   PubMed Web of Science ®Google Scholar
• Baecher-Allan, C., B. J. Kaskow, and H. L. Weiner. 2018. “Multiple Sclerosis: Mechanisms and Immunotherapy.” Neuron 97 (4): 742–768. https://doi.org/10.1016/j.neuron.2018.01.021.
   PubMed Web of Science ®Google Scholar
• Balaguer-Trias, J., D. Deepika, M. Schuhmacher, and V. Kumar. 2022. “Impact of Contaminants on Microbiota: Linking the Gut–Brain Axis with Neurotoxicity.” International Journal of Environmental Research and Public Health 19 (3): 1368. https://doi.org/10.3390/ijerph19031368.
   PubMedGoogle Scholar
• Banerjee, N., Z. T. Goodman, R. McIntosh, and G. Ironson. 2022. “Cognition, Coping, and Psychological Distress in HIV.” AIDS and Behavior 26 (4): 1074–1083. https://doi.org/10.1007/s10461-021-03462-y.
   PubMedGoogle Scholar
• Bartsch, M., A. Hahn, and S. Berkemeyer. 2023. “Bridging the Gap from Enterotypes to Personalized Dietary Recommendations: A Metabolomics Perspective on Microbiome Research.” Metabolites 13 (12): 1182. https://doi.org/10.3390/metabo13121182.
   PubMedGoogle Scholar
• Bongioanni, P., R. Del Carratore, S. Corbianco, A. Diana, G. Cavallini, S. M. Masciandaro, M. Dini, and R. Buizza. 2021. “Climate Change and Neurodegenerative Diseases.” Environmental Research 201:111511. https://doi.org/10.1016/j.envres.2021.111511.
   PubMedGoogle Scholar
• Brummelte, S., E. Mc Glanaghy, A. Bonnin, and T. F. Oberlander. 2017. “Developmental Changes in Serotonin Signaling: Implications for Early Brain Function, Behavior and Adaptation.” Neuroscience 342:212–231. https://doi.org/10.1016/j.neuroscience.2016.02.037.
   PubMed Web of Science ®Google Scholar
• Brustolin, S., R. Giugliani, and T. M. Félix. 2010. “Genetics of Homocysteine Metabolism and Associated Disorders.” Brazilian Journal of Medical & Biological Research 43 (1): 1–7. https://doi.org/10.1590/s0100-879x2009007500021.
   PubMed Web of Science ®Google Scholar
• Buckley, S., S. Byrnes, C. Cochrane, M. Roche, J. D. Estes, S. Selemidis, T. A. Angelovich, and M. J. Churchill. 2021. “The Role of Oxidative Stress in HIV-Associated Neurocognitive Disorders.” Brain, Behavior, & Immunity - Health 13:100235. https://doi.org/10.1016/j.bbih.2021.100235.
   PubMedGoogle Scholar
• Buguet, A., M. W. Radomski, J. Reis, and P. S. Spencer. 2023. “Heatwaves and Human Sleep: Stress Response Versus Adaptation.” Journal of the Neurological Sciences 454:120862. https://doi.org/10.1016/j.jns.2023.120862.
   PubMedGoogle Scholar
• Cai, C., Z. Yin, A. Liu, H. Wang, S. Zeng, Z. Wang, H. Qiu, S. Li, J. Zhou, and M. Wang. 2022. “Identifying Rare Genetic Variants of Immune Mediators as Risk Factors for Autism Spectrum Disorder.” Genes (Basel) 13 (6): 1098. https://doi.org/10.3390/genes13061098.
   PubMedGoogle Scholar
• Calcutt, N. A. 2020. “Diabetic Neuropathy and Neuropathic Pain: A (Con)fusion of Pathogenic Mechanisms?” Pain 161 (Suppl 1): S65–S86. https://doi.org/10.1097/j.pain.0000000000001922.
   PubMedGoogle Scholar
• Cammann, D., Y. Lu, M. J. Cummings, M. L. Zhang, J. M. Cue, J. Do, J. Ebersole, et al. 2023. “Genetic Correlations Between Alzheimer’s Disease and Gut Microbiome Genera.” Scientific Reports 13 (1): 5258. https://doi.org/10.1038/s41598-023-31730-5.
   PubMed Web of Science ®Google Scholar
• Carabotti, M., A. Scirocco, M. A. Maselli, and C. Severi. 2015. “The Gut-Brain Axis: Interactions Between Enteric Microbiota, Central and Enteric Nervous Systems.” Annals of Gastroenterology 28 (2): 203–209.
   PubMed Web of Science ®Google Scholar
• Chang, C. J., T. L. Lin, Y. L. Tsai, T. R. Wu, W. F. Lai, C. C. Lu, and H. C. Lai. 2019. “Next Generation Probiotics in Disease Amelioration.” Journal of Food & Drug Analysis 27 (3): 615–622. https://doi.org/10.1016/j.jfda.2018.12.011.
   PubMed Web of Science ®Google Scholar
• Chen, M., L. Xu, L. Van Horn, J. E. Manson, K. L. Tucker, X. Du, N. Feng, S. Rong, and V. W. Zhong. 2024. “Association of 8-Hour Time-Restricted Eating with All-Cause and Cause-Specific Mortality.” https://newsroom.heart.org/news/8-hour-time-restricted-eating-linked-to-a-91-higher-risk-of-cardiovascular-death?preview=cdac59c3c907975eecaef517166f08f8.
   Google Scholar
• Chen, W., J. Feng, P. Ji, Y. Liu, H. Wan, and J. Zhang. 2023. “Association of Hyperhomocysteinemia and Chronic Kidney Disease in the General Population: A Systematic Review and Meta-Analysis.” BMC nephrology 24 (1): 247. https://doi.org/10.1186/s12882-023-03295-y.
   PubMedGoogle Scholar
• Chen, Y., H. Fang, C. Li, G. Wu, T. Xu, X. Yang, L. Zhao, X. Ke, and C. Zhang. 2020. “Gut Bacteria Shared by Children and Their Mothers Associate with Developmental Level and Social Deficits in Autism Spectrum Disorder.” mSphere 5 (6): e01044–20. https://doi.org/10.1128/mSphere.01044-20.
   PubMed Web of Science ®Google Scholar
• Chiu, K., G. Warner, R. A. Nowak, J. A. Flaws, and W. Mei. 2020. “The Impact of Environmental Chemicals on the Gut Microbiome.” Toxicological Sciences 176 (2): 253–284. https://doi.org/10.1093/toxsci/kfaa065.
   PubMedGoogle Scholar
• Christovich, A., and X. M. Luo. 2022. “Gut Microbiota, Leaky Gut, and Autoimmune Diseases.” Frontiers in Immunology 13:946248. https://doi.org/10.3389/fimmu.2022.946248.
   PubMedGoogle Scholar
• Clarke, G., S. Grenham, P. Scully, P. Fitzgerald, R. D. Moloney, F. Shanahan, T. G. Dinan, and J. F. Cryan. 2013. “The Microbiome-Gut-Brain Axis During Early Life Regulates the Hippocampal Serotonergic System in a Sex-Dependent Manner.” Molecular Psychiatry 18 (6): 666–673. https://doi.org/10.1038/mp.2012.77.
   PubMed Web of Science ®Google Scholar
• Colpitts, S. L., and L. H. Kasper. 2017. “Influence of the Gut Microbiome on Autoimmunity in the Central Nervous System.” The Journal of Immunology 198 (2): 596–604. https://doi.org/10.4049/jimmunol.1601438.
   PubMed Web of Science ®Google Scholar
• Connolly, A. M., M. Chez, E. M. Streif, R. M. Keeling, P. T. Golumbek, J. M. Kwon, J. J. Riviello, R. J. Robinson, R. J. Neuman, and R. M. Deuel. 2006. “Brain-Derived Neurotrophic Factor and Autoantibodies to Neural Antigens in Sera of Children with Autistic Spectrum Disorders, Landau-Kleffner Syndrome, and Epilepsy.” Biol Psychiat 59 (4): 354–363. https://doi.org/10.1016/j.biopsych.2005.07.004.
   PubMed Web of Science ®Google Scholar
• Cordaro, M., R. Siracusa, R. Fusco, S. Cuzzocrea, R. Di Paola, and D. Impellizzeri. 2021. “Involvements of Hyperhomocysteinemia in Neurological Disorders.” Metabolites 11 (1): 37. https://doi.org/10.3390/metabo11010037.
   PubMedGoogle Scholar
• Cordeiro, C. N., M. Tsimis, and I. Burd. 2015. “Infections and Brain Development.” Obstetrical & Gynecological Survey 70 (10): 644–655. https://doi.org/10.1097/OGX.0000000000000236.
   PubMed Web of Science ®Google Scholar
• Crakes, K. R., and G. Jiang. 2019. “Gut Microbiome Alterations during HIV/SIV Infection: Implications for HIV Cure.” Frontiers in Microbiology 10:1104. https://doi.org/10.3389/fmicb.2019.01104.
   PubMed Web of Science ®Google Scholar
• Cryan, J. F., K. J. O’Riordan, K. Sandhu, V. Peterson, and T. G. Dinan. 2020. “The Gut Microbiome in Neurological Disorders.” Lancet Neurology 19 (2): 179–194. https://doi.org/10.1016/S1474-4422(19)30356-4.
   PubMed Web of Science ®Google Scholar
• Darnerud, P. O. 2003. “Toxic Effects of Brominated Flame Retardants in Man and in Wildlife.” Environment International 29 (6): 841–853. https://doi.org/10.1016/S0160-4120(03)00107-7.
   PubMed Web of Science ®Google Scholar
• Demartini, D. R., L. P. Schilling, J. C. da Costa, and C. R. Carlini. 2014. “Alzheimer’s and Parkinson’s Diseases: An Environmental Proteomic Point of View.” Journal of Proteomics 104:24–36. https://doi.org/10.1016/j.jprot.2014.04.014.
   PubMedGoogle Scholar
• Deng, L., X. Zhang, Y. Gao, D. Turner, F. Qian, H. Lu, S. H. Vermund, Y. Zhang, and H. Z. Qian. 2021. “Association of HIV Infection and Cognitive Impairment in Older Adults: A Meta-Analysis.” Ageing Research Reviews 68:101310. https://doi.org/10.1016/j.arr.2021.101310.
   PubMedGoogle Scholar
• Dethlefsen, L., S. Huse, M. L. Sogin, D. A. Relman, and J. A. Eisen. 2008. “The Pervasive Effects of an Antibiotic on the Human Gut Microbiota, as Revealed by Deep 16S rRNA Sequencing.” PLOS Biology 6 (11): e280. https://doi.org/10.1371/journal.pbio.0060280.
   PubMed Web of Science ®Google Scholar
• Dick, F. D. 2006. “Solvent Neurotoxicity.” Occupational and Environmental Medicine 63 (3): 221–226. https://doi.org/10.1136/oem.2005.022400.
   PubMed Web of Science ®Google Scholar
• DiFrancisco-Donoghue, J., E. M. Lamberg, E. Rabin, A. Elokda, E. Fazzini, and W. G. Werner. 2012. “Effects of Exercise and B Vitamins on Homocysteine and Glutathione in Parkinson’s Disease: A Randomized Trial.” Neurodegenerative Diseases 10 (1–4): 127–134. https://doi.org/10.1159/000333790.
   PubMedGoogle Scholar
• Dong, R., H. Lin, X. Chen, R. Shi, S. Yuan, J. Li, B. Zhu, et al. 2021. “Gut Microbiota and Fecal Metabolites Associated with Neurocognitive Impairment in HIV-Infected Population.” Frontiers in Cellular & Infection Microbiology 11:723840. https://doi.org/10.3389/fcimb.2021.723840.
   PubMedGoogle Scholar
• Dong, T. A., P. B. Sandesara, D. S. Dhindsa, A. Mehta, L. C. Arneson, A. L. Dollar, P. R. Taub, and L. S. Sperling. 2020. “Intermittent Fasting: A Heart Healthy Dietary Pattern?” The American Journal of Medicine 133 (8): 901–907. https://doi.org/10.1016/j.amjmed.2020.03.030).
   PubMed Web of Science ®Google Scholar
• Edmiston, E., P. Ashwood, and J. Van de Water. 2017. “Autoimmunity, Autoantibodies, and Autism Spectrum Disorder.” Biological psychiatry 81 (5): 383–390. https://doi.org/10.1016/j.biopsych.2016.08.031.
   PubMed Web of Science ®Google Scholar
• El-Ansary, A., G. Bjørklund, S. Chirumbolo, and O. M. Alnakhli. 2017. “Predictive Value of Selected Biomarkers Related to Metabolism and Oxidative Stress in Children with Autism Spectrum Disorder.” Metabolic Brain Disease 32 (4): 1209–1221. https://doi.org/10.1007/s11011-017-0029-x.
   PubMed Web of Science ®Google Scholar
• Endoh, K., M. Murakami, T. Sugiyama, Y. Taki, and K. Umegaki. 2007. “Low Folate Status Enhanced Benzene-Induced Cytogenetic Damage in Bone Marrow of Mice: A Relationship Between Dietary Intake and Tissue Levels of Folate.” Nutrition and Cancer 59 (1): 99–105. https://doi.org/10.1080/01635580701419048.
   PubMed Web of Science ®Google Scholar
• Engen, P. A., S. J. Green, R. M. Voigt, C. B. Forsyth, and A. Keshavarzian. 2015. “The Gastrointestinal Microbiome: Alcohol Effects on the Composition of Intestinal Microbiota.” Alcohol Research: Current Reviews 37 (2): 223–236.
   PubMed Web of Science ®Google Scholar
• Eshraghi, R. S., R. C. Deth, R. Mittal, M. Aranke, S. S. Kay, B. Moshiree, and A. A. Eshraghi. 2018. “Early Disruption of the Microbiome Leading to Decreased Antioxidant Capacity and Epigenetic Changes: Implications for the Rise in a Autism.” Frontiers in Cellular Neuroscience 12:256. https://doi.org/10.3389/fncel.2018.00256.
   PubMed Web of Science ®Google Scholar
• Esser, C. 1994. “Dioxins and the Immune System: Mechanisms of Interference. A Meeting Report.” International Archives of Allergy & Immunology 104 (2): 126–130. https://doi.org/10.1159/000236719.
   PubMedGoogle Scholar
• Fakharian, F., S. Thirugnanam, D. A. Welsh, W. K. Kim, J. Rappaport, K. Bittinger, and N. Rout. 2023. “The Role of Gut Dysbiosis in the Loss of Intestinal Immune Cell Functions and Viral Pathogenesis.” Microorganisms 11 (7): 1849. https://doi.org/10.3390/microorganisms11071849.
   PubMedGoogle Scholar
• Faroon, O., N. Roney, J. Taylor, A. Ashizawa, M. H. Lumpkin, and D. J. Plewak. 2008. “Acrolein Health Effects.” Toxicology and Industrial Health 24 (7): 447–490. https://doi.org/10.1177/0748233708094188.
   PubMedGoogle Scholar
• Fearon, I. M. 2014. “Risk Factors, Oxidative Stress, and Cardiovascular Disease.” In Systems Biology of Free Radicals and Antioxidants, edited by I. Laher, 765–790. Berlin, Heidelberg: Springer. https://doi.org/10.1007/978-3-642-30018-9_46.
   Google Scholar
• Fischer, T. Z., and S. G. Waxman. 2010. “Neuropathic Pain in Diabetes—Evidence for a Central Mechanism.” Nature Reviews Neurology 6 (8): 462–426. https://doi.org/10.1038/nrneurol.2010.90.
   PubMedGoogle Scholar
• Flora, S. J., S. Chouhan, G. M. Kannan, M. Mittal, and H. Swarnkar. 2008. “Combined Administration of Taurine and Monoisoamyl DMSA Protects Arsenic Induced Oxidative Injury in Rats.” Oxidative Medicine and Cellular Longevity 1 (1): 39–45. https://doi.org/10.4161/oxim.1.1.6481.
   PubMed Web of Science ®Google Scholar
• Fonnum, F., E. Mariussen, and T. Reistad. 2006. “Molecular Mechanisms Involved in the Toxic Effects of Polychlorinated Biphenyls (PCBs) and Brominated Flame Retardants (BFRs).” Journal of Toxicology and Environmental Health Part A 69 (1–2): 21–35. https://doi.org/10.1080/15287390500259020.
   PubMed Web of Science ®Google Scholar
• Francino, M. P. 2016. “Antibiotics and the Human Gut Microbiome: Dysbioses and Accumulation of Resistances.” Frontiers in Microbiology 6:1543. https://doi.org/10.3389/fmicb.2015.01543.
   PubMed Web of Science ®Google Scholar
• Galland, C., C. Dupuy, V. Loizeau, M. Danion, M. Auffret, L. Quiniou, J. Laroche, and V. Pichereau. 2015. “Proteomic Analysis of the European Flounder Platichthys Flesus Response to Experimental PAH–PCB Contamination.” Marine Pollution Bulletin 95 (2): 646–657. https://doi.org/10.1016/j.marpolbul.2015.04.038.
   PubMedGoogle Scholar
• Gamble, M. V., X. Liu, H. Ahsan, R. Pilsner, V. Ilievski, V. Slavkovich, F. Parvez, D. Levy, P. Factor-Litvak, and J. H. Graziano. 2005. “Folate, Homocysteine, and Arsenic Metabolism in Arsenic-Exposed Individuals in Bangladesh.” Environmental Health Perspectives 113 (12): 1683–1688. https://doi.org/10.1289/ehp.8084.
   PubMedGoogle Scholar
• Ganguly, P., and S. F. Alam. 2015. “Role of Homocysteine in the Development of Cardiovascular Disease.” Nutrition journal 14 (1): 6. https://doi.org/10.1186/1475-2891-14-6.
   PubMed Web of Science ®Google Scholar
• Giongo, A., K. A. Gano, D. B. Crabb, N. Mukherjee, L. L. Novelo, G. Casella, J. C. Drew, et al. 2011. “Toward Defining the Autoimmune Microbiome for Type 1 Diabetes.” The ISME Journal 5 (1): 82–91. https://doi.org/10.1038/ismej.2010.92.
   PubMed Web of Science ®Google Scholar
• Griffiths, J. A., and S. K. Mazmanian. 2018. “Emerging Evidence Linking the Gut Microbiome to Neurologic Disorders.” Genome Medicine 10 (1): 98. https://doi.org/10.1186/s13073-018-0609-3.
   PubMed Web of Science ®Google Scholar
• Gulani, A., and T. Weiler. 2023. “Genetics, autosomal recessive. [Updated 2023 May 1].” In StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. 2024. https://www.ncbi.nlm.nih.gov/books/NBK546620/.
   Google Scholar
• Habib, S. S., T. Al-Khlaiwi, A. Almushawah, A. Alsomali, and S. A. Habib. 2023. “Homocysteine As a Predictor and Prognostic Marker of Atherosclerotic Cardiovascular Disease: A Systematic Review and Meta-Analysis.” European Review for Medical and Pharmacological Sciences 27 (18): 8598–8608. https://doi.org/10.26355/eurrev_202309_33784.
   PubMedGoogle Scholar
• Hablitz, L. M., and M. Nedergaard. 2021. “The Glymphatic System: A Novel Component of Fundamental Neurobiology.” Journal of Neuroscience 41 (37): 7698–7711. https://doi.org/10.1523/JNEUROSCI.0619-21.2021.
   PubMedGoogle Scholar
• Hall, M. B., D. E. Willis, E. L. Rodriguez, and J. M. Schwarz. 2023. “Maternal Immune Activation As an Epidemiological Risk Factor for Neurodevelopmental Disorders: Considerations of Timing, Severity, Individual Differences, and Sex in Human and Rodent Studies.” Frontiers in Neuroscience 17:1135559. https://doi.org/10.3389/fnins.2023.1135559.
   PubMedGoogle Scholar
• Heidari, H., and D. A. Lawrence. 2023. “Climate Stressors and Physiological Dysregulations: Mechanistic Connections to p Athologies.” International Journal of Environmental Research and Public Health 21 (1): 28. https://doi.org/10.3390/ijerph21010028.
   PubMedGoogle Scholar
• Hemarajata, P., and J. Versalovic. 2013. “Effects of Probiotics on Gut Microbiota: Mechanisms of Intestinal Immunomodulation and Neuromodulation.” Therapeutic Advances in Gastroenterology 6 (1): 39–51. https://doi.org/10.1177/1756283X12459294.
   PubMed Web of Science ®Google Scholar
• Hirano, T., and H. Nakase. 2021. “The Multifaceted Effects of Gut Microbiota on the Immune System of the Intestinal Mucosa.” Immunology 1 (4): 583–594. https://doi.org/10.3390/immuno1040041.
   Google Scholar
• Hirayama, M., and K. Ohno. 2021. “Parkinson’s Disease and Gut Microbiota.” Annals of Nutrition & Metabolism 77 (Suppl 2): 28–35. https://doi.org/10.1159/000518147.
   PubMedGoogle Scholar
• Hirt, N., and M. Body-Malapel. 2020. “Immunotoxicity and Intestinal Effects of Nano- and Microplastics: A Review of the Literature.” Particle and Fibre Toxicology 17 (1): 57. https://doi.org/10.1186/s12989-020-00387-7.
   PubMed Web of Science ®Google Scholar
• Hodgkinson, K., F. E. Abbar, P. Dobranowski, J. Manoogian, J. Butcher, D. Figeys, D. Mack, and A. Stintzi. 2023. “Butyrate’s Role in Human Health and the Current Progress Towards Its Clinical Application to Treat Gastrointestinal Disease.” Clinical Nutrition 42 (2): 61–75. https://doi.org/10.1016/j.clnu.2022.10.024.
   PubMedGoogle Scholar
• Hooper, L. V., D. R. Littman, and A. J. Macpherson. 2012. “Interactions Between the Microbiota and the Immune System.” Science 336 (6086): 1268–1273. https://doi.org/10.1126/science.1223490.
   PubMed Web of Science ®Google Scholar
• Hou, M., G. Xu, M. Ran, W. Luo, and H. Wang. 2021. “APOE-ε4 Carrier Status and Gut Microbiota Dysbiosis in Patients with Alzheimer Disease.” Frontiers in Neuroscience 15:619051. https://doi.org/10.3389/fnins.2021.619051.
   PubMedGoogle Scholar
• Hsieh, T. H., C. W. Kuo, K. H. Hsieh, M. J. Shieh, C. W. Peng, Y. C. Chen, Y. L. Chang, et al. 2020. “Probiotics Alleviate the Progressive Deterioration of Motor Functions in a Mouse Model of Parkinson’s Disease.” Brain Sciences 10 (4): 206. https://doi.org/10.3390/brainsci10040206.
   PubMed Web of Science ®Google Scholar
• Hu, J., C. Lesseur, Y. Miao, F. Manservisi, S. Panzacchi, D. Mandrioli, F. Belpoggi, J. Chen, and L. Petrick. 2021. “Low-Dose Exposure of Glyphosate-Based Herbicides Disrupt the Urine Metabolome and Its Interaction with Gut Microbiota.” Scientific Reports 11 (1): 3265. https://doi.org/10.1038/s41598-021-82552-2.
   PubMedGoogle Scholar
• Huang, B., S. W. H. Chau, Y. Liu, J. W. Y. Chan, J. Wang, S. L. Ma, J. Zhang, et al. 2023. “Gut Microbiome Dysbiosis Across Early Parkinson’s Disease, REM Sleep Behavior Disorder and Their First-Degree Relatives.” Nature Communications 14 (1): 2501. https://doi.org/10.1038/s41467-023-38248-4.
   PubMedGoogle Scholar
• Hughes, H. K., E. Mills Ko, D. Rose, and P. Ashwood. 2018. “Immune Dysfunction and Autoimmunity As Pathological Mechanisms in Autism Spectrum Disorders.” Frontiers in Cellular Neuroscience 12:405. https://doi.org/10.3389/fncel.2018.00405.
   PubMed Web of Science ®Google Scholar
• Israelyan, N., and K. G. Margolis. 2019. “Reprint Of: Serotonin As a Link Between the Gut-Brain-Microbiome Axis in Autism Spectrum Disorders.” Pharmacological Research 140:115–120. https://doi.org/10.1016/j.phrs.2018.12.023.
   PubMedGoogle Scholar
• Ivanov, A. V., V. T. Valuev-Elliston, O. N. Ivanova, S. N. Kochetkov, E. S. Starodubova, B. Bartosch, and M. G. Isaguliants. 2016. “Oxidative Stress During HIV Infection: Mechanisms and Consequences.” Oxidative Medicine and Cellular Longevity 2016:1–18. https://doi.org/10.1155/2016/8910396.
   Google Scholar
• James, S. J., P. Cutler, S. Melnyk, S. Jernigan, L. Janak, D. W. Gaylor, and J. A. Neubrander. 2004. “Metabolic Biomarkers of Increased Oxidative Stress and Impaired Methylation Capacity in Children with Autism.” The American Journal of Clinical Nutrition 80 (6): 1611–1617. https://doi.org/10.1093/ajcn/80.6.1611.
   PubMed Web of Science ®Google Scholar
• Janssen, A. W., and S. Kersten. 2015. “The Role of the Gut Microbiota in Metabolic Health.” Federation of American Societies for Experimental Biology Journal 29 (8): 3111–3123. https://doi.org/10.1096/fj.14-269514.
   PubMed Web of Science ®Google Scholar
• Jantsch, J., I. D. Tassinari, M. Giovenardi, V. Bambini-Junior, R. P. Guedes, and L. S. de Fraga. 2022. “Mood Disorders Induced by Maternal Overnutrition: The Role of the Gut-Brain Axis on the Development of Depression and Anxiety.” Frontiers in Cell and Developmental Biology 10:795384. https://doi.org/10.3389/fcell.2022.795384.
   PubMedGoogle Scholar
• Jernberg, C., S. Löfmark, C. Edlund, and J. K. Jansson. 2010. “Long-Term Impacts of Antibiotic Exposure on the Human Intestinal Microbiota.” Microbiology (Reading) 156 (11): 3216–3223. https://doi.org/10.1099/mic.0.040618-0.
   PubMedGoogle Scholar
• Jia, X., Q. Chen, Y. Zhang, and T. Asakawa. 2023. “Multidirectional Associations Between the Gut Microbiota and Parkinson’s Disease, Updated Information from the Perspectives of Humoral Pathway, Cellular Immune Pathway and Neuronal Pathway.” Frontiers in Cellular & Infection Microbiology 13:1296713. https://doi.org/10.3389/fcimb.2023.1296713.
   PubMedGoogle Scholar
• Jiang, L., J. C. Li, B. S. Tang, and J. F. Guo. 2023. “Associations Between Gut Microbiota and Parkinson Disease: A Bidirectional Mendelian Randomization Analysis.” European Journal of Neurology 30 (11): 3471–3477. https://doi.org/10.1111/ene.15848.
   PubMedGoogle Scholar
• Kahanovitz, L., P. M. Sluss, and S. J. Russell. 2017. “Type 1 Diabetes—A Clinical Perspective.” Point of Care: The Journal of Near-Patient Testing & Technology 16 (1): 37–40. https://doi.org/10.1097/POC.0000000000000125.
   Google Scholar
• Kandpal, M., O. Indari, B. Baral, S. Jakhmola, D. Tiwari, V. Bhandari, R. K. Pandey, K. Bala, A. Sonawane, and H. C. Jha. 2022. “Dysbiosis of Gut Microbiota from the Perspective of the Gut–Brain Axis: Role in the Provocation of Neurological Disorders.” Metabolites 12 (11): 1064. https://doi.org/10.3390/metabo12111064.
   PubMed Web of Science ®Google Scholar
• Kim, J., H. Kim, H. Roh, and Y. Kwon. 2018. “Causes of Hyperhomocysteinemia and Its Pathological Significance.” Archives of Pharmacal Research 41 (4): 372–383. https://doi.org/10.1007/s12272-018-1016-4.
   PubMed Web of Science ®Google Scholar
• Kinashi, Y., and K. Hase. 2021. “Partners in Leaky Gut Syndrome: Intestinal Dysbiosis and Autoimmunity.” Frontiers in Immunology 12:673708. https://doi.org/10.3389/fimmu.2021.673708.
   PubMedGoogle Scholar
• Koay, W. L. A., L. V. Siems, and D. Persaud. 2018. “The Microbiome and HIV Persistence: Implications for Viral Remission and Cure.” Current Opinion in HIV and AIDS 13 (1): 61–68. https://doi.org/10.1097/COH.0000000000000434.
   PubMed Web of Science ®Google Scholar
• Kojta, I., M. Chacińska, and A. Błachnio-Zabielska. 2020. “Obesity, Bioactive Lipids, and Adipose Tissue Inflammation in Insulin Resistance.” Nutrients 12 (5): 1305. https://doi.org/10.3390/nu12051305.
   PubMed Web of Science ®Google Scholar
• Kuo, C. C., K. A. Moon, S. L. Wang, E. Silbergeld, and A. Navas-Acien. 2017. “The Association of Arsenic Metabolism with Cancer, Cardiovascular Disease, and Diabetes: A Systematic Review of the Epidemiological Evidence.” Environmental Health Perspectives 125 (8): 087001. https://doi.org/10.1289/EHP577.
   PubMed Web of Science ®Google Scholar
• Lavezzi, A. M., and B. Ramos-Molina. 2023. “Environmental Exposure Science and Human Health.” International Journal of Environmental Research and Public Health 20 (10): 5764. https://doi.org/10.3390/ijerph20105764.
   PubMedGoogle Scholar
• Lawrence, D. A., A. Jadhav, T. K. Mondal, K. Carson, W. T. Lee, A. H. Hogan, K. W. Herbst, I. C. Michelow, M. Brimacombe, and J. C. Salazar. 2024. “Inflammatory and Autoimmune Aspects of Multisystem Inflammatory Syndrome in Children (MIS-C): A Prospective Cohort Study.” Viruses 16 (6): 950. https://doi.org/10.3390/v16060950.
   PubMedGoogle Scholar
• Ledda, C., E. Cannizzaro, P. Lovreglio, E. Vitale, A. Stufano, A. Montana, G. Li Volti, and V. Rapisarda. 2019. “Exposure to Toxic Heavy Metals Can Influence Homocysteine Metabolism?” Antioxidants (Basel) 9 (1): 30. https://doi.org/10.3390/antiox9010030.
   PubMedGoogle Scholar
• Lee, C. J., C. L. Sears, and N. Maruthur. 2020. “Gut Microbiome and Its Role in Obesity and Insulin Resistance.” Annals of the New York Academy of Sciences 1461 (1): 37–52. https://doi.org/10.1111/nyas.14107.
   PubMed Web of Science ®Google Scholar
• Lee, P. I., and P. R. Hsueh. 2023. “Multisystem Inflammatory Syndrome in Children: A Dysregulated Autoimmune Disorder Following COVID-19.” Journal of Microbiology, Immunology, and Infection 56 (2): 236–245. https://doi.org/10.1016/j.jmii.2023.01.001.
   Google Scholar
• Lee, S. H. F., S. R. Ahmad, Y. C. Lim, and I. N. Zulkipli. 2022. “The Use of Probiotic Therapy in Metabolic and Neurological Diseases.” Frontiers in Nutrition 9:887019. https://doi.org/10.3389/fnut.2022.887019.
   PubMedGoogle Scholar
• Lei, M., R. Menon, S. Manteiga, N. Alden, C. Hunt, R. C. Alaniz, K. Lee, and A. Jayaraman. 2019. “Environmental Chemical Diethylhexyl Phthalate Alters Intestinal Microbiota Community Structure and Metabolite Profile in Mice.” mSystems 4 (6): e00724–19. https://doi.org/10.1128/mSystems.00724-19.
   PubMedGoogle Scholar
• Li, H., H. Li, Z. Zhu, X. Xiong, Y. Huang, Y. Feng, Z. Li, K. Wu, and F. Wu. 2023. “Association of Serum Homocysteine Levels with Intestinal Flora and Cognitive Function in Schizophrenia.” Journal of Psychiatric Research 159:258–265. https://doi.org/10.1016/j.jpsychires.2023.01.045.
   PubMedGoogle Scholar
• Liew, W. P., and S. Mohd-Redzwan. 2018. “Mycotoxin: Its Impact on Gut Health and Microbiota.” Frontiers in Cellular & Infection Microbiology 8:60. https://doi.org/10.3389/fcimb.2018.00060.
   PubMed Web of Science ®Google Scholar
• Liu, S., X. Deng, Z. Li, W. Zhou, G. Wang, J. Zhan, and B. Hu. 2023. “Environmental Cadmium Exposure Alters the Internal Microbiota and Metabolome of Sprague–Dawley Rats.” Frontiers in Veterinary Science 10:1219729. https://doi.org/10.3389/fvets.2023.1219729.
   PubMedGoogle Scholar
• Liu, S., J. Gao, M. Zhu, K. Liu, and H. L. Zhang. 2020. “Gut Microbiota and Dysbiosis in Alzheimer’s Disease: Implications for Pathogenesis and Treatment.” Molecular Neurobiology 57 (12): 5026–5043. https://doi.org/10.1007/s12035-020-02073-3.
   PubMed Web of Science ®Google Scholar
• Liu, Y., Y. Baba, T. Ishimoto, X. Gu, J. Zhang, D. Nomoto, K. Okadome, H. Baba, and P. Qiu. 2022. “Gut Microbiome in Gastrointestinal Cancer: A Friend or Foe?” International Journal of Biological Sciences 18 (10): 4101–4117. https://doi.org/10.7150/ijbs.69331.
   PubMedGoogle Scholar
• López-Vargas, R., A. Méndez-Serrano, A. Albores-Medina, F. Oropeza-Hernández, L. Hernández-Cadena, F. Mercado-Calderón, E. Alvarado-Toledo, et al. 2018. “Oxidative Stress Index Is Increased in Children Exposed to Industrial Discharges and Is Inversely Correlated with Metabolite Excretion of VOC.” Environmental and Molecular Mutagenesis 59 (7): 639–652. https://doi.org/10.1002/em.22207.
   PubMedGoogle Scholar
• Lucock, M. 2000. “Folic Acid: Nutritional Biochemistry, Molecular Biology, and Role in Disease Processes.” Molecular Genetics and Metabolism 71 (1–2): 121–138. https://doi.org/10.1006/mgme.2000.3027.
   PubMed Web of Science ®Google Scholar
• Lyche, J. L., A. C. Gutleb, A. Bergman, G. S. Eriksen, A. J. Murk, E. Ropstad, M. Saunders, and J. U. Skaare. 2009. “Reproductive and Developmental Toxicity of Phthalates.” Journal of Toxicology and Environmental Health Part B 12 (4): 225–249. https://doi.org/10.1080/10937400903094091.
   PubMed Web of Science ®Google Scholar
• Ma, B.-Q., J.-X. Jia, H. Wang, S.-J. Li, Z.-J. Yang, X.-Y. Wang, and X.-S. Yan. 2024. “Cannabidiol Improves the Cognitive Function of SAMP8 AD Model Mice Involving the Microbiota -Gut-Brain Axis.” Journal of Toxicology and Environmental Health Part A 87 (11): 471–479. https://doi.org/10.1080/15287394.2024.2338914.
   PubMedGoogle Scholar
• Madore, C., Q. Leyrolle, C. Lacabanne, A. Benmamar-Badel, C. Joffre, A. Nadjar, and S. Layé. 2016. “Neuroinflammation in Autism: Plausible Role of Maternal Inflammation, Dietary Omega 3, and Microbiota.” Neural Plasticity 2016:1–15. https://doi.org/10.1155/2016/3597209.
   Google Scholar
• Mallah, M. A., L. Changxing, M. A. Mallah, S. Noreen, Y. Liu, M. Saeed, H. Xi, et al. 2022. “Polycyclic Aromatic Hydrocarbon and Its Effects on Human Health: An Overview.” Chemosphere 296:133948. https://doi.org/10.1016/j.chemosphere.2022.133948.
   PubMed Web of Science ®Google Scholar
• Maltz-Matyschsyk, M., C. K. Melchiorre, K. W. Herbst, A. H. Hogan, K. Dibble, B. O’Sullivan, J. Graf, et al. 2023. “Connecticut Children’s COVID Collaborative. Development of a Biomarker Signature Using Grating-Coupled Fluorescence Plasmonic Microarray for Diagnosis of MIS-C.” Frontiers in Bioengineering and Biotechnology 11:1066391. https://doi.org/10.3389/fbioe.2023.1066391.
   PubMedGoogle Scholar
• Manivasagam, T., S. Arunadevi, M. M. Essa, C. SaravanaBabu, A. Borah, A. J. Thenmozhi, and M. W. Qoronfleh. 2020. “Role of Oxidative Stress and Antioxidants in Autism.” Adv Neurobiol 24:193–206. https://doi.org/10.1007/978-3-030-30402-7_7.
   PubMedGoogle Scholar
• Manos, J. 2022. “The Human Microbiome in Disease and Pathology.” APMIS 130 (12): 690–705. https://doi.org/10.1111/apm.13225.
   PubMedGoogle Scholar
• Martins-Silva, T., A. Salatino-Oliveira, J. P. Genro, F. D. T. Meyer, Y. Li, L. A. Rohde, M. H. Hutz, and L. Tovo-Rodrigues. 2021. “Host Genetics Influences the Relationship Between the Gut Microbiome and Psychiatric Disorders.” Progress in Neuro-Psychopharmacology & Biological Psychiatry 106:110153. https://doi.org/10.1016/j.pnpbp.2020.110153.
   PubMedGoogle Scholar
• Meek, T. H., and G. J. Morton. 2012. “Leptin, Diabetes, and the Brain.” Indian Journal of Endocrinology and Metabolism 16 (Suppl 3): S534–S542. https://doi.org/10.4103/2230-8210.105568.
   PubMedGoogle Scholar
• Mendelsohn, A. R., and J. W. Larrick. 2013. “Dietary Modification of the Microbiome Affects Risk for Cardiovascular Disease.” Rejuvenation Research 16 (3): 241–244. https://doi.org/10.1089/rej.2013.1447.
   PubMedGoogle Scholar
• Mittal, R., and C. M. Coopersmith. 2014. “Redefining the Gut as the Motor of Critical Illness.” Trends in Molecular Medicine 20 (4): 214–223. https://doi.org/10.1016/j.molmed.2013.08.004.
   PubMed Web of Science ®Google Scholar
• Molina, J. D., S. Avila, G. Rubio, and F. López-Muñoz. 2021. “Metabolomic Connections Between Schizophrenia, Antipsychotic Drugs and Metabolic Syndrome: A Variety of Players.” Current Pharmaceutical Design 27 (39): 4049–4061. https://doi.org/10.2174/1381612827666210804110139.
   PubMed Web of Science ®Google Scholar
• Moscavitch, S. D., M. Szyper-Kravitz, and Y. Shoenfeld. 2009. “Autoimmune Pathology Accounts for Common Manifestations in a Wide Range of Neuro-Psychiatric Disorders: The Olfactory and Immune System Interrelationship.” Clinical Immunology 130 (3): 235–243. https://doi.org/10.1016/j.clim.2008.10.010.
   PubMedGoogle Scholar
• Moshal, K. S., N. Metreveli, I. Frank, and S. C. Tyagi. 2008. “Mitochondrial MMP Activation, Dysfunction and Arrhythmogenesis in Hyperhomocysteinemia.” nCurrent Vascular Pharmacology 6 (2): 84–92. https://doi.org/10.2174/157016108783955301.
   PubMedGoogle Scholar
• Nagpal, R., R. Mainali, S. Ahmadi, S. Wang, R. Singh, K. Kavanagh, D. W. Kitzman, A. Kushugulova, F. Marotta, and H. Yadav. 2018. “Gut Microbiome and Aging: Physiological and Mechanistic Insights.” Nutrition and Healthy Aging 4 (4): 267–285. https://doi.org/10.3233/NHA-170030.
   PubMedGoogle Scholar
• Naidoo, N. 2009. “Cellular Stress/The Unfolded Protein Response: Relevance to Sleep and Sleep Disorders.” Sleep Medicine Reviews 13 (3): 195–204. https://doi.org/10.1016/j.smrv.2009.01.001.
   PubMedGoogle Scholar
• Needham, B. D., W. Tang, and W. L. Wu. 2018. “Searching for the Gut Microbial Contributing Factors to Social Behavior in Rodent Models of Autism Spectrum Disorder.” Developmental Neurobiology 78 (5): 474–499. https://doi.org/10.1002/dneu.22581.
   PubMedGoogle Scholar
• Neghab, M., K. Hosseinzadeh, and J. Hassanzadeh. 2015. “Early Liver and Kidney Dysfunction Associated with Occupational Exposure to Sub-Threshold Limit Value Levels of Benzene, Toluene, and Xylenes in Unleaded Petrol.” Safety and Health at Work 6 (4): 312–316. https://doi.org/10.1016/j.shaw.2015.07.008.
   PubMedGoogle Scholar
• Negro, A., J. L. Seidel, T. Houben, E. S. Yu, I. Rosen, A. J. Arreguin, N. Yalcin, et al. 2020. “Acute Sleep Deprivation Enhances Susceptibility to the Migraine Substrate Cortical Spreading Depolarization.” The Journal of Headache and Pain 21 (1): 86. https://doi.org/10.1186/s10194-020-01155-w.
   PubMed Web of Science ®Google Scholar
• Newell, C., M. R. Bomhof, R. A. Reimer, D. S. Hittel, J. M. Rho, and J. Shearer. 2016. “Ketogenic Diet Modifies the Gut Microbiota in a Murine Model of Autism Spectrum Disorder.” Molecular Autism 7 (1): 37. https://doi.org/10.1186/s13229-016-0099-3.
   PubMedGoogle Scholar
• Obradovic, M., E. Sudar-Milovanovic, S. Soskic, M. Essack, S. Arya, A. J. Stewart, T. Gojobori, and E. R. Isenovic. 2021. “Leptin and Obesity: Role and Clinical Implication.” Frontiers in Endocrinology 12:585887. https://doi.org/10.3389/fendo.2021.585887.
   PubMed Web of Science ®Google Scholar
• Obrenovich, M., B. Siddiqui, B. McCloskey, and V. P. Reddy. 2020. “The Microbiota–Gut–Brain Axis Heart Shunt Part I: The French Paradox, Heart Disease and the Microbiota.” Microorganisms 8 (4): 490. https://doi.org/10.3390/microorganisms8040490.
   PubMedGoogle Scholar
• Ogbodo, J. O., A. V. Arazu, T. C. Iguh, N. J. Onwodi, and T. C. Ezike. 2022. “Volatile Organic Compounds: A Proinflammatory Activator in Autoimmune Diseases.” Frontiers in Immunology 13:928379. https://doi.org/10.3389/fimmu.2022.928379.
   PubMedGoogle Scholar
• Ohkawara, T., T. Katsuyama, M. Ida-Eto, N. Narita, and M. Narita. 2015. “Maternal Viral Infection During Pregnancy Impairs Development of Fetal Serotonergic Neurons.” Brain & Development 37 (1): 88–93. https://doi.org/10.1016/j.braindev.2014.03.007.
   PubMedGoogle Scholar
• O’Mahony, S. M., G. Clarke, Y. E. Borre, T. G. Dinan, and J. F. Cryan. 2015. “Serotonin, Tryptophan Metabolism and the Brain-Gut-Microbiome Axis.” Behavioural Brain Research 277:32–48. https://doi.org/10.1016/j.bbr.2014.07.027.
   PubMed Web of Science ®Google Scholar
• Ouyang, Y., Q. Wu, J. Li, S. Sun, and S. Sun. 2020. “S-Adenosylmethionine: A Metabolite Critical to the Regulation of Autophagy.” Cell Proliferation 53 (11): e12891. https://doi.org/10.1111/cpr.12891.
   PubMed Web of Science ®Google Scholar
• Pálsson, R., and U. D. Patel. 2014. “Cardiovascular Complications of Diabetic Kidney Disease.” Advances in Chronic Kidney Disease 21 (3): 273–280. https://doi.org/10.1053/j.ackd.2014.03.003.
   PubMed Web of Science ®Google Scholar
• Parker, A., S. Fonseca, and S. R. Carding. 2020. “Gut Microbes and Metabolites As Modulators of Blood-Brain Barrier Integrity and Brain Health.” Gut Microbes 11 (2): 135–157. https://doi.org/10.1080/19490976.2019.1638722.
   PubMed Web of Science ®Google Scholar
• Patterson, P. H. 2009. “Immune Involvement in Schizophrenia and Autism: Etiology, Pathology and Animal Models.” Behavioural Brain Research 204 (2): 313–321. https://doi.org/10.1016/j.bbr.2008.12.016.
   PubMed Web of Science ®Google Scholar
• Pérez-Pérez, A., F. Sánchez-Jiménez, T. Vilariño-García, and V. Sánchez-Margalet. 2020. “Role of Leptin in Inflammation and Vice Versa.” International Journal of Molecular Sciences 21 (16): 5887. https://doi.org/10.3390/ijms21165887.
   PubMed Web of Science ®Google Scholar
• Peterson, C. T. 2020. “Dysfunction of the Microbiota-Gut-Brain Axis in Neurodegenerative Disease: The Promise of Therapeutic Modulation with Prebiotics, Medicinal Herbs, Probiotics, and Synbiotics.” Journal of Evidence-Based Integrative Medicine 25:2515690X20957225. https://doi.org/10.1177/2515690X20957225.
   PubMedGoogle Scholar
• Peterson, L. W., and D. Artis. 2014. “Intestinal Epithelial Cells: Regulators of Barrier Function and Immune Homeostasis.” Nature Reviews Immunology 14 (3): 141–153. https://doi.org/10.1038/nri3608.
   PubMed Web of Science ®Google Scholar
• Petit, J. M., E. Eren-Koçak, H. Karatas, P. Magistretti, and T. Dalkara. 2021. “Brain Glycogen Metabolism: A Possible Link Between Sleep Disturbances, Headache and Depression.” Sleep Medicine Reviews 59:101449. https://doi.org/10.1016/j.smrv.2021.101449.
   PubMedGoogle Scholar
• Petriello, M. C., J. B. Hoffman, M. Sunkara, B. Wahlang, J. T. Perkins, A. J. Morris, and B. Hennig. 2016. “Dioxin-Like Pollutants Increase Hepatic Flavin Containing Monooxygenase (FMO3) Expression to Promote Synthesis of the Pro-Atherogenic Nutrient Biomarker Trimethylamine N-Oxide from Dietary Precursors.” The Journal of Nutritional Biochemistry 33:145–153. https://doi.org/10.1016/j.jnutbio.2016.03.016.
   PubMed Web of Science ®Google Scholar
• Pickard, J. M., M. Y. Zeng, R. Caruso, and G. Núñez. 2017. “Gut Microbiota: Role in Pathogen Colonization, Immune Responses, and Inflammatory Disease.” Immunological Reviews 279 (1): 70–89. https://doi.org/10.1111/imr.12567.
   PubMed Web of Science ®Google Scholar
• Picó, C., M. Palou, C. A. Pomar, A. M. Rodríguez, and A. Palou. 2022. “Leptin As a Key Regulator of the Adipose Organ.” Reviews in Endocrine & Metabolic Disorders 23 (1): 13–30. https://doi.org/10.1007/s11154-021-09687-5.
   PubMedGoogle Scholar
• Pollack, A. Z., S. L. Mumford, L. Sjaarda, N. J. Perkins, F. Malik, J. Wactawski-Wende, and E. F. Schisterman. 2017. “Blood Lead, Cadmium and Mercury in Relation to Homocysteine and C-Reactive Protein in Women of Reproductive Age: A Panel Study.” Environmental Health 16 (1): 84. https://doi.org/10.1186/s12940-017-0293-6.
   PubMedGoogle Scholar
• Porritt, R. A., A. Binek, L. Paschold, M. N. Rivas, A. McArdle, L. M. Yonker, G. Alter, et al. 2021. “The Autoimmune Signature of Hyperinflammatory Multisystem Inflammatory Syndrome in Children.” Journal of Clinical Investigation 131 (20): e151520. https://doi.org/10.1172/JCI151520.
   PubMedGoogle Scholar
• Pushpakumar, S., S. Kundu, and U. Sen. 2014. “Endothelial Dysfunction: The Link Between Homocysteine and Hydrogen Sulfide.” Current Vascular Pharmacology 21 (32): 3662–3672. https://doi.org/10.2174/0929867321666140706142335.
   Google Scholar
• Qureshi, I. A., and M. F. Mehler. 2013. “Towards a ‘Systems’-Level Understanding of the Nervous System and Its Disorders.” Trends in Neurosciences 36 (11): 674–684. https://doi.org/10.1016/j.tins.2013.07.003.
   PubMedGoogle Scholar
• Ren, J. C., Y. X. Wu, Z. Wu, G. H. Zhang, H. Wang, H. Liu, J. P. Cui, et al. 2018. “MTHFR Gene Polymorphism Is Associated with DNA Hypomethylation and Genetic Damage Among Benzene-Exposed Workers in Southeast China.” Journal of Occupational and Environmental Medicine 60 (4): e188–e192. https://doi.org/10.1097/JOM.0000000000001288.
   PubMedGoogle Scholar
• Rich, S., E. Klann, V. Bryant, V. Richards, A. Wijayabahu, K. Bryant, V. Mai, and R. Cook. 2020. “A Review of Potential Microbiome-Gut-Brain Axis Mediated Neurocognitive Conditions in Persons Living with HIV.” Brain, Behavior, & Immunity - Health 9:100168. https://doi.org/10.1016/j.bbih.2020.100168.
   PubMedGoogle Scholar
• Rizowy, G. M., S. Poloni, K. Colonetti, K. C. Donis, P. T. Dobbler, S. Leistner-Segal, L. F. W. Roesch, and I. V. D. Schwartz. 2020. “Is the Gut Microbiota Dysbiotic in Patients with Classical Homocystinuria?” Biochimie 173:3–11. https://doi.org/10.1016/j.biochi.2020.02.013.
   PubMedGoogle Scholar
• Romagnani, S., and E. Maggi. 1994. “Th1 versus Th2 Responses in AIDS.” Current Opinion in Immunology 6 (4): 616–622. https://doi.org/10.1016/0952-7915(94)90150-3.
   PubMedGoogle Scholar
• Rudzki, L., L. Ostrowska, D. Pawlak, A. Małus, K. Pawlak, N. Waszkiewicz, and A. Szulc. 2019. “Probiotic Lactobacillus Plantarum 299v Decreases Kynurenine Concentration and Improves Cognitive Functions in Patients with Major Depression: A Double-Blind, Randomized, Placebo Controlled Study.” Psychoneuroendocrinology 100:213–222. https://doi.org/10.1016/j.psyneuen.2018.10.010.
   PubMed Web of Science ®Google Scholar
• Rutsch, A., J. B. Kantsjö, and F. Ronchi. 2020. “The Gut-Brain Axis: How Microbiota and Host Inflammasome Influence Brain Physiology and Pathology.” Frontiers in Immunology 11:604179. https://doi.org/10.3389/fimmu.2020.604179.
   PubMed Web of Science ®Google Scholar
• Sacharow, S. J., J. D. Picker, and H. L. Levy. 2017. “Homocystinuria Caused by Cystathionine Beta-Synthase Deficiency. 2004 [Updated 2017].” In Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, Editors. GeneReviews® [Internet], 1993–2024. Seattle (WA): University of Washington, Seattle.
   Google Scholar
• Salim, S. Y., G. G. Kaplan, and K. L. Madsen. 2014. “Air Pollution Effects on the Gut Microbiota: A Link Between Exposure and Inflammatory Disease.” Gut Microbes 5 (2): 215–219. https://doi.org/10.4161/gmic.27251.
   PubMed Web of Science ®Google Scholar
• Salimi, A., B. S. Talatappe, and J. Pourahmad. 2017. “Xylene Induces Oxidative Stress and Mitochondria Damage in Isolated Human Lymphocytes.” Toxicological Research 33 (3): 233–238. https://doi.org/10.5487/TR.2017.33.3.233.
   PubMed Web of Science ®Google Scholar
• Samji, H., J. Wu, A. Ladak, C. Vossen, E. Stewart, N. Dove, D. Long, and G. Snell. 2022. “Review: Mental Health Impacts of the COVID-19 Pandemic on Children and Youth – a Systematic Review.” Child and Adolescent Mental Health 27 (2): 173–189. https://doi.org/10.1111/camh.12501.
   PubMed Web of Science ®Google Scholar
• Santos, S. F., H. L. de Oliveira, E. S. Yamada, B. C. Neves, and A. Pereira Jr. 2019. “The Gut and Parkinson’s Disease—A Bidirectional Pathway.” Frontiers in Neurology 10:574. https://doi.org/10.3389/fneur.2019.00574.
   PubMedGoogle Scholar
• Schéle, E., L. Grahnemo, F. Anesten, A. Hallén, F. Bäckhed, and J. O. Jansson. 2013. “The Gut Microbiota Reduces Leptin Sensitivity and the Expression of the Obesity-Suppressing Neuropeptides Proglucagon (Gcg) and Brain-Derived Neurotrophic Factor (Bdnf) in the Central Nervous System.” Endocrinology 154 (10): 3643–3651. https://doi.org/10.1210/en.2012-2151.
   PubMed Web of Science ®Google Scholar
• Schertzer, J. D., and T. K. T. Lam. 2021. “Peripheral and Central Regulation of Insulin by the Intestine and Microbiome.” American Journal of Physiology-Endocrinology & Metabolism 320 (2): E234–E239. https://doi.org/10.1152/ajpendo.00547.2020.
   PubMedGoogle Scholar
• Shabbir, U., M. S. Arshad, A. Sameen, and D. H. Oh. 2021. “Crosstalk Between Gut and Brain in Alzheimer’s Disease: The Role of Gut Microbiota Modulation Strategies.” Nutrients 13 (2): 690. https://doi.org/10.3390/nu13020690.
   PubMed Web of Science ®Google Scholar
• Shukla, U. V., and K. Tripathy. 2023. “Diabetic Retinopathy.” In StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing.
   Google Scholar
• Shum, T. F., L. Wang, and J. Chiou. 2023. “Impact of Plasticizer on the Intestinal Epithelial Integrity and Tissue-Repairing Ability within Cells in the Proximity of the Human Gut M Icrobiome.” International Journal of Environmental Research and Public Health 20 (3): 2152. https://doi.org/10.3390/ijerph20032152.
   PubMedGoogle Scholar
• Socała, K., U. Doboszewska, A. Szopa, A. Serefko, M. Włodarczyk, A. Zielińska, E. Poleszak, J. Fichna, and P. Wlaź. 2021. “The Role of Microbiota-Gut-Brain Axis in Neuropsychiatric and Neurological Disorders.” Pharmacological Research 172:105840. https://doi.org/10.1016/j.phrs.2021.105840.
   PubMed Web of Science ®Google Scholar
• Suganya, K., and B. S. Koo. 2020. “Gut–Brain Axis: Role of Gut Microbiota on Neurological Disorders and How Probiotics/Prebiotics Beneficially Modulate Microbial and Immune Pathways to Improve Brain Functions.” International Journal of Molecular Sciences 21 (20): 7551. https://doi.org/10.3390/ijms21207551.
   PubMedGoogle Scholar
• Sun, R., M. Cao, J. Zhang, W. Yang, H. Wei, X. Meng, L. Yin, and Y. Pu. 2016. “Benzene Exposure Alters Expression of Enzymes Involved in Fatty Acid β-Oxidation in Male C3H/He Mice.” International Journal of Environmental Research and Public Health 13 (11): 1068. https://doi.org/10.3390/ijerph13111068.
   PubMedGoogle Scholar
• Sunder-Plassmann, G., W. C. Winkelmayer, and M. Födinger. 2006. “Genetic Aspects of Hyperhomocysteinemia in Chronic Kidney Disease.” Seminars in Nephrology 26 (1): 8–13. https://doi.org/10.1016/j.semnephrol.2005.06.003.
   PubMedGoogle Scholar
• Suskun, C., O. Kilic, D. Yilmaz Ciftdogan, S. Guven, A. Karbuz, A. Ozkaya Parlakay, Y. Kara, et al. 2022. “Intestinal Microbiota Composition of Children with Infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Multisystem Inflammatory Syndrome (MIS-C).” European Journal of Pediatrics 181 (8): 3175–3191. https://doi.org/10.1007/s00431-022-04494-9.
   PubMedGoogle Scholar
• Takeuchi, T., T. Kubota, Y. Nakanishi, H. Tsugawa, W. Suda, A. T. Kwon, J. Yazaki, et al. 2023. “Gut Microbial Carbohydrate Metabolism Contributes to Insulin Resistance.” Nature 621 (7978): 389–395. https://doi.org/10.1038/s41586-023-06466-x.
   PubMed Web of Science ®Google Scholar
• Takiishi, T., C. I. M. Fenero, and N. O. S. Câmara. 2017. “Intestinal Barrier and Gut Microbiota: Shaping Our Immune Responses Throughout Life.” Tissue Barriers 5 (4): e1373208. https://doi.org/10.1080/21688370.2017.1373208.
   PubMed Web of Science ®Google Scholar
• Taniya, M. A., H. J. Chung, A. Al Mamun, S. Alam, M. A. Aziz, N. U. Emon, M. M. Islam, et al. 2022. “Role of Gut Microbiome in Autism Spectrum Disorder and Its Therapeutic Regulation.” Frontiers in Cellular & Infection Microbiology 12:915701. https://doi.org/10.3389/fcimb.2022.915701.
   PubMed Web of Science ®Google Scholar
• Teqegne, B. A., and B. Kebede. 2022. “Probiotics, Their Prophylactic and Therapeutic Applications in Human Health Development: A Review of the Literature.” Heliyon 8 (6): e09725. https://doi.org/10.1016/j.heliyon.2022.e09725.
   PubMedGoogle Scholar
• Teratani, T., Y. Mikami, N. Nakamoto, T. Suzuki, Y. Harada, K. Okabayashi, Y. Hagihara, et al. 2020. “The Liver–Brain–Gut Neural Arc Maintains the Treg Cell Niche in the Gut.” Nature 585 (7826): 591–596. https://doi.org/10.1038/s41586-020-2425-3.
   PubMedGoogle Scholar
• Tsuyuki, K., A. N. Cimino, C. N. Holliday, J. C. Campbell, N. A. Al-Alusi, and J. K. Stockman. 2019. “Physiological Changes from Violence-Induced Stress and Trauma Enhance HIV Susceptibility Among Women.” Current HIV/AIDS Reports 16 (1): 57–65. https://doi.org/10.1007/s11904-019-00435-8.
   PubMed Web of Science ®Google Scholar
• Uddin, M. N., K. Manley, and D. A. Lawrence. 2022. “Altered Meningeal Immunity Contributing to the Autism-Like Behavior of BTBR T+Itpr3tf /J Mice.” Brain, Behavior, & Immunity - Health 26:100563. https://doi.org/10.1016/j.bbih.2022.100563.
   PubMedGoogle Scholar
• Uddin, M. N., Y. Yao, T. K. Mondal, R. Matala, K. Manley, Q. Lin, and D. A. Lawrence. 2020. “Immunity and Autoantibodies of a Mouse Strain with Autistic-Like Behavior.” Brain, Behavior, & Immunity - Health 4:100069. https://doi.org/10.1016/j.bbih.2020.100069.
   PubMedGoogle Scholar
• Ullah, H., S. Arbab, Y. Tian, C. Q. Liu, Y. Chen, L. Qijie, M. I. U. Khan, I. U. Hassan, and K. Li. 2023. “The Gut Microbiota–Brain Axis in Neurological Disorder.” Frontiers in Neuroscience 17:1225875. https://doi.org/10.3389/fnins.2023.1225875.
   PubMedGoogle Scholar
• Van Dyken, P., and B. Lacoste. 2018. “Impact of Metabolic Syndrome on Neuroinflammation and the Blood–Brain Barrier.” Frontiers in Neuroscience 12:930. https://doi.org/10.3389/fnins.2018.00930.
   PubMed Web of Science ®Google Scholar
• van Son, J., L. L. Koekkoek, S. E. La Fleur, M. J. Serlie, and M. Nieuwdorp. 2021. “The Role of the Gut Microbiota in the Gut–Brain Axis in Obesity: Mechanisms and Future Implications.” International Journal of Molecular Sciences 22 (6): 2993. https://doi.org/10.3390/ijms22062993.
   PubMedGoogle Scholar
• Varady, K. A., S. Lin, V. M. Oddo, and S. Cienfuegos. 2024. “Debunking the Myths of Intermittent Fasting.” Nature Reviews Endocrinology. https://doi.org/10.1038/s41574-024-01009-4.
   PubMedGoogle Scholar
• Varady, K. A., M. C. Runchey, S. Reutrakul, A. P. Vidmar, and L. S. Chow. 2024. “Clinical Potential of Fasting in Type 1 Diabetes.” Trends in Endocrinology & Metabolism S1043-2760(24) 00021-3.35 (5): 413–424. https://doi.org/10.1016/j.tem.2024.01.007.
   PubMedGoogle Scholar
• Waligóra, A., S. Waligóra, M. Kozarska, A. Damasiewicz-Bodzek, P. Gorczyca, and K. Tyrpień-Golder. 2019. “Autism Spectrum Disorder (ASD) – Biomarkers of Oxidative Stress and Methylation and Transsulfuration Cycle.” Psychiatria polska 53 (4): 771–788. https://doi.org/10.12740/PP/89948.
   PubMedGoogle Scholar
• Wang, B. K., and W. L. Chen. 2022. “Detrimental Health Relationship Between Blood Lead and Cadmium and the Red Blood Cell Folate Level.” Scientific Reports 12 (1): 6628. https://doi.org/10.1038/s41598-022-10562-9.
   PubMedGoogle Scholar
• Wang, Q., Y. Luo, K. Ray Chaudhuri, R. Reynolds, E. K. Tan, and S. Pettersson. 2021. “The Role of Gut Dysbiosis in Parkinson’s Disease: Mechanistic Insights and Therapeutic Options.” Brain A Journal of Neurology 144 (9): 2571–2593. https://doi.org/10.1093/brain/awab156.
   PubMedGoogle Scholar
• Wang, R., R. Tang, B. Li, X. Ma, B. Schnabl, and H. Tilg. 2021. “Gut Microbiome, Liver Immunology, and Liver Diseases.” Cellular & Molecular Immunology 18 (1): 4–17. https://doi.org/10.1038/s41423-020-00592-6.
   PubMed Web of Science ®Google Scholar
• Wang, X., C. J. Menezes, Y. Jia, Y. Xiao, S. S. K. Venigalla, F. Cai, M. H. Hsieh, et al. 2024. “Metabolic Inflexibility Promotes Mitochondrial Health During Liver Regeneration.” Science 384 (6701): eadj4301. https://doi.org/10.1126/science.adj4301.
   PubMedGoogle Scholar
• Wang, X., P. Zhang, and X. Zhang. 2021. “Probiotics Regulate Gut Microbiota: An Effective Method to Improve Immunity.” Molecules 26 (19): 6076. https://doi.org/10.3390/molecules26196076.
   PubMed Web of Science ®Google Scholar
• Wijekoon, E. P., M. E. Brosnan, and J. T. Brosnan. 2007. “Homocysteine Metabolism in Diabetes.” Biochemical Society Transactions 35 (5): 1175–1179. https://doi.org/10.1042/BST0351175.
   PubMedGoogle Scholar
• Williams, K. T., and K. L. Schalinske. 2010. “Homocysteine Metabolism and Its Relation to Health and Disease.” Biofactors 36 (1): 19–24. https://doi.org/10.1002/biof.71.
   PubMedGoogle Scholar
• Xu, R., J. W. Cao, H. L. Lv, Y. Geng, and M. Y. Guo. 2024. “Polyethylene Microplastics Induced Gut Microbiota Dysbiosis Leading to Liver Injury via the TLR2/NF-κB/NLRP3 Pathway in Mice.” Science of the Total Environment 917:170518. https://doi.org/10.1016/j.scitotenv.2024.170518.
   PubMedGoogle Scholar
• Yakub, M., M. P. Iqbal, and R. Iqbal. 2010. “Dietary Patterns Are Associated with Hyperhomocysteinemia in an Urban Pakistani Population.” The Journal of Nutrition 140 (7): 1261–1266. https://doi.org/10.3945/jn.109.120477.
   PubMedGoogle Scholar
• Yan, M., S. Man, B. Sun, L. Ma, L. Guo, L. Huang, and W. Gao. 2023. “Gut Liver Brain Axis in Diseases: The Implications for Therapeutic Interventions.” Signal Transduction and Targeted Therapy 8 (1): 443. https://doi.org/10.1038/s41392-023-01673-4.
   PubMed Web of Science ®Google Scholar
• Yang, K., L. Li, Y. Wang, and J. Liu. 2020. “Effects of Substrate Fluctuation on the Performance, Microbial Community and Metabolic Function of a Biofilter for Gaseous Dichloromethane Treatment.” Chemosphere 249:126185. https://doi.org/10.1016/j.chemosphere.2020.126185.
   PubMedGoogle Scholar
• Yao, Y., M. N. Uddin, K. Manley, and D. A. Lawrence. 2022. “Improvements of Autism-Like Behaviors but Limited Effects on Immune Cell Metabolism After Mitochondrial Replacement in BTBR T+Itpr3tf/J Mice.” Journal of Neuroimmunology 368:577893. https://doi.org/10.1016/j.jneuroim.2022.577893.
   PubMedGoogle Scholar
• Yi, T., S. P. Gao, T. Zhu, H. Yin, and S. Jin. 2022. “Glymphatic System Dysfunction: A Novel Mediator of Sleep Disorders and Headaches.” Frontiers in Neurology 13:885020. https://doi.org/10.3389/fneur.2022.885020.).
   PubMedGoogle Scholar
• Yu, L., X. Hu, H. Li, and Y. Zhao. 2022. “Perivascular Spaces, Glymphatic System and MR.” Frontiers in Neurology 13:844938. https://doi.org/10.3389/fneur.2022.844938.
   PubMedGoogle Scholar
• Zhang, F., J. Yang, Y. Ji, M. Sun, J. Shen, J. Sun, J. Wang, et al. 2019. “Gut Microbiota Dysbiosis Is Not Independently Associated with Neurocognitive Impairment in People Living with HIV.” Frontiers in Microbiology 9. https://doi.org/10.3389/fmicb.2018.03352.
   Google Scholar
• Zhang, L., H. Kang, W. Zhang, J. Wang, Z. Liu, J. Jing, L. Han, and A. Gao. 2023. “Probiotics Ameliorate Benzene-Induced Systemic Inflammation and Hematopoietic Toxicity by Inhibiting Bacteroidaceae-Mediated Ferroptosis.” Science of the Total Environment 899:165678. https://doi.org/10.1016/j.scitotenv.2023.165678.
   PubMedGoogle Scholar
• Zhang, L., Y. Liu, Y. Sun, and X. Zhang. 2022. “Combined Physical Exercise and Diet: Regulation of Gut Microbiota to Prevent and Treat of Metabolic Disease: A Review.” Nutrients 14 (22): 4774. https://doi.org/10.3390/nu14224774.
   PubMedGoogle Scholar
• Zhang, P. 2022. “Influence of Foods and Nutrition on the Gut Microbiome and Implications for Intestinal Health.” International Journal of Molecular Sciences 23 (17): 9588. https://doi.org/10.3390/ijms23179588.
   PubMedGoogle Scholar
• Zhao, X., X. An, C. Yang, W. Sun, H. Ji, and F. Lian. 2023. “The Crucial Role and Mechanism of Insulin Resistance in Metabolic Disease.” Frontiers in Endocrinology 14:1149239. https://doi.org/10.3389/fendo.2023.1149239.
   PubMed Web of Science ®Google Scholar
• Zhou, A., Y. Yuan, M. Yang, Y. Huang, X. Li, S. Li, S. Yang, and B. Tang. 2022. “Crosstalk Between the Gut Microbiota and Epithelial Cells Under Physiological and Infectious Conditions.” Frontiers in Cellular & Infection Microbiology 12:832672. https://doi.org/10.3389/fcimb.2022.832672.
   PubMedGoogle Scholar
• Zhou, H., L. Sun, S. Zhang, X. Zhao, X. Gang, and G. Wang. 2020. “Evaluating the Causal Role of Gut Microbiota in Type 1 Diabetes and Its Possible Pathogenic Mechanisms.” Frontiers in Endocrinology 11:125. https://doi.org/10.3389/fendo.2020.00125.
   PubMedGoogle Scholar
• Zhou, P., C. Chen, S. Patil, and S. Dong. 2024. “Unveiling the Therapeutic Symphony of Probiotics, Prebiotics, and Postbiotics in Gut-Immune Harmony.” Frontiers in Nutrition 11:1355542. https://doi.org/10.3389/fnut.2024.1355542.
   PubMedGoogle Scholar
• Zhu, L., B. Zhang, Y. Dai, H. Li, and W. Xu. 2017. “A Review: Epigenetic Mechanism in Ochratoxin a Toxicity Studies.” Toxins (Basel) 9 (4): 113. https://doi.org/10.3390/toxins9040113.
   PubMedGoogle Scholar
• Zundler, S., C. Günther, A. E. Kremer, M. M. Zaiss, V. Rothhammer, and M. F. Neurath. 2023. “Gut Immune Cell Trafficking: Inter-Organ Communication and Immune-Mediated Inflammation.” Nature Reviews Gastroenterology & Hepatology 20 (1): 50–64. https://doi.org/10.1038/s41575-022-00663-1.
   PubMedGoogle Scholar