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image of Early-Life Microbiome and Neurodevelopmental Disorders: A Systematic Review and Meta-Analysis

Abstract

Background and Objectives

This systematic review intends to find out how neurodevelopmental disorders, including Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD), are influenced by the gut microbiota throughout early childhood. The study looks at the variety and types of microbes that a child is exposed to, the particular microbiome profiles associated with neurodevelopmental outcomes, and the molecular processes that underlie these relationships.

Methods

We performed a thorough search of PubMed, Scopus, the WHO Global Health Library (GHL), and ISI Web of Science. After screening 2,744 original studies based on predetermined eligibility criteria, 19 studies were included. Microbial groupings, presence (high/low), and related neurodevelopmental disorders were among the primary areas of data extraction. The methodological quality of the studies was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS).

Results

The investigated literature repeatedly showed a strong correlation between dysbiosis of the gut microbiota and neurodevelopmental disorders. Cases of ASD were associated with both a high number of species and a low number of species. On the other hand, a Low number of and a high number of the class phylum , genus and as well as the species , , and have been linked to ADHD. The NOS evaluation showed variation in the quality of the methodology; some studies had high scores, suggesting sound technique, while other studies had lower scores, indicating serious methodological flaws.

Conclusion

The results highlight the potential impact of the gut microbiome throughout early life on neurodevelopmental outcomes, indicating that microbial imbalances may play a role in the onset of disorders like ASD and ADHD. However, to improve the quality of data, larger-scale longitudinal studies would be required.

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2025-05-26
2025-09-13
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References

  1. Whitman W.B. Coleman D.C. Wiebe W.J. Prokaryotes: The unseen majority. Proc. Natl. Acad. Sci. USA 1998 95 12 6578 6583 10.1073/pnas.95.12.6578 9618454
    [Google Scholar]
  2. Zhu X. Han Y. Du J. Liu R. Jin K. Yi W. Microbiota-gut-brain axis and the central nervous system. Oncotarget 2017 8 32 53829 53838 10.18632/oncotarget.17754 28881854
    [Google Scholar]
  3. Principi N. Esposito S. Gut microbiota and central nervous system development. J. Infect. 2016 73 6 536 546 10.1016/j.jinf.2016.09.010 27725185
    [Google Scholar]
  4. Sorboni S.G. Moghaddam H.S. Jafarzadeh-Esfehani R. Soleimanpour S. A comprehensive review on the role of the gut microbiome in human neurological disorders. Clin. Microbiol. Rev. 2022 35 1 e00338 e20 10.1128/CMR.00338‑20 34985325
    [Google Scholar]
  5. Battle D.E. Diagnostic and statistical manual of mental disorders (DSM). CoDAS 2013 25 2 191 192 10.1590/S2317‑17822013000200017 24413388
    [Google Scholar]
  6. Muhle R.A. Reed H.E. Stratigos K.A. Veenstra-VanderWeele J. The emerging clinical neuroscience of autism spectrum disorder. JAMA Psychiatry 2018 75 5 514 523 10.1001/jamapsychiatry.2017.4685 29590280
    [Google Scholar]
  7. Thomas R. Sanders S. Doust J. Beller E. Glasziou P. Prevalence of attention-deficit/hyperactivity disorder: A systematic review and meta-analysis. Pediatrics 2015 135 4 e994 e1001 10.1542/peds.2014‑3482 25733754
    [Google Scholar]
  8. Posner J. Polanczyk G.V. Sonuga-Barke E. Attention-deficit hyperactivity disorder. Lancet 2020 395 10222 450 462 10.1016/S0140‑6736(19)33004‑1 31982036
    [Google Scholar]
  9. Borre Y.E. O’Keeffe G.W. Clarke G. Stanton C. Dinan T.G. Cryan J.F. Microbiota and neurodevelopmental windows: Implications for brain disorders. Trends Mol. Med. 2014 20 9 509 518 10.1016/j.molmed.2014.05.002 24956966
    [Google Scholar]
  10. Clarke G. Grenham S. Scully P. Fitzgerald P. Moloney R.D. Shanahan F. Dinan T.G. Cryan J.F. The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Mol. Psychiatry 2013 18 6 666 673 10.1038/mp.2012.77 22688187
    [Google Scholar]
  11. Hsiao E.Y. McBride S.W. Hsien S. Sharon G. Hyde E.R. McCue T. Codelli J.A. Chow J. Reisman S.E. Petrosino J.F. Patterson P.H. Mazmanian S.K. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 2013 155 7 1451 1463 10.1016/j.cell.2013.11.024 24315484
    [Google Scholar]
  12. Warner B.B. The contribution of the gut microbiome to neurodevelopment and neuropsychiatric disorders. Pediatr. Res. 2019 85 2 216 224 10.1038/s41390‑018‑0191‑9 30283047
    [Google Scholar]
  13. Lacorte E. Gervasi G. Bacigalupo I. Vanacore N. Raucci U. Parisi P. A systematic review of the microbiome in children with neurodevelopmental disorders. Front. Neurol. 2019 10 727 10.3389/fneur.2019.00727 31417479
    [Google Scholar]
  14. Homberg J.R. Kolk S.M. Schubert D. Editorial perspective of the research topic “deciphering serotonin’s role in neurodevelopment”. Front. Cell. Neurosci. 2013 7 212 10.3389/fncel.2013.00212 24302896
    [Google Scholar]
  15. Kim C.S. Roles of diet-associated gut microbial metabolites on brain health: Cell-to-cell interactions between gut bacteria and the central nervous system. Adv. Nutr. 2024 15 1 100136 100136 10.1016/j.advnut.2023.10.008 38436218
    [Google Scholar]
  16. Barroso A. Mahler J.V. Fonseca-Castro P.H. Quintana F.J. The aryl hydrocarbon receptor and the gut-brain axis. Cell. Mol. Immunol. 2021 18 2 259 268 10.1038/s41423‑020‑00585‑5 33408340
    [Google Scholar]
  17. Colonna M. Butovsky O. Microglia function in the central nervous system during health and neurodegeneration. Annu. Rev. Immunol. 2017 35 1 441 468 10.1146/annurev‑immunol‑051116‑052358 28226226
    [Google Scholar]
  18. Chen B-R. Wu T. Chen T-H. Wang Y. Neuroimmune interactions and their roles in neurodegenerative diseases. Fundam. Res. 2024 4 2 251 261 10.1016/j.fmre.2023.04.002
    [Google Scholar]
  19. Tremlett H. Waubant E. Gut microbiome and pediatric multiple sclerosis. Mult. Scler. 2018 24 1 64 68 10.1177/1352458517737369 29307301
    [Google Scholar]
  20. Carabotti M. Scirocco A. Maselli M.A. Severi C. The gut-brain axis: Interactions between enteric microbiota, central and enteric nervous systems. Ann. Gastroenterol. 2015 28 2 203 209 25830558
    [Google Scholar]
  21. Gao K. Mu C. Farzi A. Zhu W. Tryptophan metabolism: A link between the gut microbiota and brain. Adv. Nutr. 2020 11 3 709 723 10.1093/advances/nmz127 31825083
    [Google Scholar]
  22. Chen Y. Xu J. Chen Y. Regulation of neurotransmitters by the gut microbiota and effects on cognition in neurological disorders. Nutrients 2021 13 6 2099 10.3390/nu13062099 34205336
    [Google Scholar]
  23. Rutsch A. Kantsjö J.B. Ronchi F. The gut-brain axis: How microbiota and host inflammasome influence brain physiology and pathology. Front. Immunol. 2020 11 604179 10.3389/fimmu.2020.604179 33362788
    [Google Scholar]
  24. Rogers G.B. Keating D.J. Young R.L. Wong M-L. Licinio J. Wesselingh S. From gut dysbiosis to altered brain function and mental illness: Mechanisms and pathways. Mol. Psychiatry 2016 21 6 738 748 10.1038/mp.2016.50 27090305
    [Google Scholar]
  25. Grochowska M. Wojnar M. Radkowski M. The gut microbiota in neuropsychiatric disorders. Acta Neurobiol. Exp. 2018 78 2 69 81 10.21307/ane‑2018‑008 30019700
    [Google Scholar]
  26. Sampson T.R. Debelius J.W. Thron T. Janssen S. Shastri G.G. Ilhan Z.E. Challis C. Schretter C.E. Rocha S. Gradinaru V. Chesselet M.F. Keshavarzian A. Shannon K.M. Krajmalnik-Brown R. Wittung-Stafshede P. Knight R. Mazmanian S.K. Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson’s disease. Cell 2016 167 6 1469 1480.e12 10.1016/j.cell.2016.11.018 27912057
    [Google Scholar]
  27. de Theije C.G.M. Wopereis H. Ramadan M. van Eijndthoven T. Lambert J. Knol J. Garssen J. Kraneveld A.D. Oozeer R. Altered gut microbiota and activity in a murine model of autism spectrum disorders. Brain Behav. Immun. 2014 37 197 206 10.1016/j.bbi.2013.12.005 24333160
    [Google Scholar]
  28. Kang D.W. Adams J.B. Gregory A.C. Borody T. Chittick L. Fasano A. Khoruts A. Geis E. Maldonado J. McDonough-Means S. Pollard E.L. Roux S. Sadowsky M.J. Lipson K.S. Sullivan M.B. Caporaso J.G. Krajmalnik-Brown R. Microbiota transfer therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: An open-label study. Microbiome 2017 5 1 10 10.1186/s40168‑016‑0225‑7 28122648
    [Google Scholar]
  29. Polanczyk G.V. Salum G.A. Sugaya L.S. Caye A. Rohde L.A. Annual research review: A meta of the worldwide prevalence of mental disorders in children and adolescents. J. Child Psychol. Psychiatry 2015 56 3 345 365 10.1111/jcpp.12381 25649325
    [Google Scholar]
  30. Polanczyk G.V. Willcutt E.G. Salum G.A. Kieling C. Rohde L.A. ADHD prevalence estimates across three decades: An updated systematic review and meta-regression analysis. Int. J. Epidemiol. 2014 43 2 434 442 10.1093/ije/dyt261 24464188
    [Google Scholar]
  31. Nøvik T.S. Hervas A. Ralston S.J. Dalsgaard S. Rodrigues Pereira R. Lorenzo M.J. Influence of gender on attentiondeficit/hyperactivity disorder in Europe--ADORE. Eur Child Adolesc Psychiatry 2006 15 S1 i15 i24 10.1007/s00787‑006‑1003‑z 17177011
    [Google Scholar]
  32. Lai M.C. Lombardo M.V. Baron-Cohen S. Autism. Lancet 2014 383 9920 896 910 10.1016/S0140‑6736(13)61539‑1 24074734
    [Google Scholar]
  33. Whittaker R.H. Evolution and measurement of species diversity. Taxon 1972 21 2-3 213 251 10.2307/1218190
    [Google Scholar]
  34. Sordillo J.E. Korrick S. Laranjo N. Carey V. Weinstock G.M. Gold D.R. O’Connor G. Sandel M. Bacharier L.B. Beigelman A. Zeiger R. Litonjua A.A. Weiss S.T. Association of the infant gut microbiome with early childhood neurodevelopmental outcomes. JAMA Netw. Open 2019 2 3 e190905 10.1001/jamanetworkopen.2019.0905 30901046
    [Google Scholar]
  35. Tamana S.K. Tun H.M. Konya T. Chari R.S. Field C.J. Guttman D.S. Becker A.B. Moraes T.J. Turvey S.E. Subbarao P. Sears M.R. Pei J. Scott J.A. Mandhane P.J. Kozyrskyj A.L. Bacteroides-dominant gut microbiome of late infancy is associated with enhanced neurodevelopment. Gut Microbes 2021 13 1 1930875 10.1080/19490976.2021.1930875 34132157
    [Google Scholar]
  36. Gao W. Salzwedel A.P. Carlson A.L. Xia K. Azcarate-Peril M.A. Styner M.A. Thompson A.L. Geng X. Goldman B.D. Gilmore J.H. Knickmeyer R.C. Gut microbiome and brain functional connectivity in infants-a preliminary study focusing on the amygdala. Psychopharmacology 2019 236 5 1641 1651 10.1007/s00213‑018‑5161‑8 30604186
    [Google Scholar]
  37. Tomlinson M.S. Santos H.P. Stewart J.R. Joseph R. Leviton A. Onderdonk A.B. Kuban K.C.K. Heeren T. O’Shea T.M. Fry R.C. Shah B. Singh R. Van Marter L. Martin C. Ware J. Cole C. Perrin E. Bednarek F. Frazier J.A. Ehrenkranz R. Benjamin J. O’Shea T.M. Bose C. Warner D. Engelke S. Poortenga M. Pastyrnak S. Karna P. Paneth N. Lenski M. Schreiber M. Hunter S. Msall M. Batton D. Klarr J. Christianson K. Klein D. Pimental M. Hallisey C. Coster T. Nylen E. Neger E. Mattern K. Venuti L. Powers B. Foley A. Williams J. Romano E. Hiatt D. Peters N. Brown P. Ansusinha E. Bose G. Wereszczak J. Bernhardt J. Adams J. Wilson D. Darden-Saad N. Sutton D. Rathbun J. Miras K. Weiland D. Yoon G. Ramoskaite R. Wiggins S. Washington K. Martin R. Prendergast B. Kring B. Smith A. McQuiston S. Butler S. Wilson R. McGhee K. Lee P. Asgarian A. Sadhwani A. Henson B. Keller C. Walkowiak J. Barron S. Miller A. Dessureau B. Wood M. Damon-Minow J. Romano E. Mayes L. Tsatsanis K. Chawarska K. Kim S. Dieterich S. Bearrs K. Waldrep E. Friedman J. Hounshell G. Allred D. Helms R. Whitley L. Stainback G. Bostic L. Jacobson A. McKeeman J. Meyer E. Pastyrnak S. Price J. Lloyd M. Plesha-Troyke S. Scott M. Solomon K.M. Brooklier K. Vogt K. Neurocognitive and social-communicative function of children born very preterm at 10 years of age: Associations with microorganisms recovered from the Placenta parenchyma. J. Perinatol. 2020 40 2 306 315 10.1038/s41372‑019‑0505‑8 31624322
    [Google Scholar]
  38. Hursitoglu M. Kural A. Kuras S. Akdeniz E. Sezer S. Caypinar S.S. Kazezoglu C. Yaprak B. Karandere F. Guven H.Z. Maternal gut microbiota in pregnancies resulting in down syndrome newborns - A pilot study. Acta Clin. Croat. 2021 60 4 722 730 10.20471/acc.2021.60.04.20 35734495
    [Google Scholar]
  39. Zuffa S. Schimmel P. Gonzalez-Santana A. Belzer C. Knol J. Bölte S. Falck-Ytter T. Forssberg H. Swann J. Diaz Heijtz R. Early-life differences in the gut microbiota composition and functionality of infants at elevated likelihood of developing autism spectrum disorder. Transl. Psychiatry 2023 13 1 257 10.1038/s41398‑023‑02556‑6 37443359
    [Google Scholar]
  40. Sun Z. Xu W. Cong X. Li G. Chen K. Log-contrast regression with functional compositional predictors: Linking preterm infants’ gut microbiome trajectories to neurobehavioral outcome. Ann. Appl. Stat. 2020 14 3 1535 1556 10.1214/20‑AOAS1357 34163544
    [Google Scholar]
  41. Cassidy-Bushrow A.E. Sitarik A.R. Johnson C.C. Johnson-Hooper T.M. Kassem Z. Levin A.M. Lynch S.V. Ownby D.R. Phillips J.M. Yong G.J.M. Wegienka G. Straughen J.K. Early-life gut microbiota and attention deficit hyperactivity disorder in preadolescents. Pediatr. Res. 2023 93 7 2051 2060 10.1038/s41390‑022‑02051‑6 35440767
    [Google Scholar]
  42. Oliphant K. Ali M. D’Souza M. Hughes P.D. Sulakhe D. Wang A.Z. Xie B. Yeasin R. Msall M.E. Andrews B. Claud E.C. Bacteroidota and Lachnospiraceae integration into the gut microbiome at key time points in early life are linked to infant neurodevelopment. Gut Microbes 2021 13 1 1997560 10.1080/19490976.2021.1997560 34839801
    [Google Scholar]
  43. Sun Z. Lee-Sarwar K. Kelly R.S. Lasky-Su J.A. Litonjua A.A. Weiss S.T. Liu Y.Y. Revealing the importance of prenatal gut microbiome in offspring neurodevelopment in humans. EBioMedicine 2023 90 104491 10.1016/j.ebiom.2023.104491 36868051
    [Google Scholar]
  44. Axelsson P.B. Clausen T.D. Petersen A.H. Hageman I. Pinborg A. Kessing L.V. Bergholt T. Rasmussen S.C. Keiding N. Løkkegaard E.C.L. Investigating the effects of cesarean delivery and antibiotic use in early childhood on risk of later attention deficit hyperactivity disorder. J. Child Psychol. Psychiatry 2019 60 2 151 159 10.1111/jcpp.12961 30136734
    [Google Scholar]
  45. Wang M. Zhou J. He F. Cai C. Wang H. Wang Y. Lin Y. Rong H. Cheng G. Xu R. Zhou W. Alteration of gut microbiota-associated epitopes in children with autism spectrum disorders. Brain Behav. Immun. 2019 75 192 199 10.1016/j.bbi.2018.10.006 30394313
    [Google Scholar]
  46. Senn E. Symeonides C. Vuillermin P. Ponsonby A.L. Early life microbial exposure, child neurocognition and behaviour at 2 years of age: A birth cohort study. J. Paediatr. Child Health 2020 56 4 590 599 10.1111/jpc.14695 31782587
    [Google Scholar]
  47. Kelsey C.M. Prescott S. McCulloch J.A. Trinchieri G. Valladares T.L. Dreisbach C. Alhusen J. Grossmann T. Gut microbiota composition is associated with newborn functional brain connectivity and behavioral temperament. Brain Behav. Immun. 2021 91 472 486 10.1016/j.bbi.2020.11.003 33157257
    [Google Scholar]
  48. Carissimi C. Laudadio I. Palone F. Fulci V. Cesi V. Cardona F. Alfonsi C. Cucchiara S. Isoldi S. Stronati L. Functional analysis of gut microbiota and immunoinflammation in children with autism spectrum disorders. Dig. Liver Dis. 2019 51 10 1366 1374 10.1016/j.dld.2019.06.006 31320306
    [Google Scholar]
  49. Carlson A.L. Xia K. Azcarate-Peril M.A. Goldman B.D. Ahn M. Styner M.A. Thompson A.L. Geng X. Gilmore J.H. Knickmeyer R.C. Infant gut microbiome associated with cognitive development. Biol. Psychiatry 2018 83 2 148 159 10.1016/j.biopsych.2017.06.021 28793975
    [Google Scholar]
  50. Sanctuary M.R. Kain J.N. Chen S.Y. Kalanetra K. Lemay D.G. Rose D.R. Yang H.T. Tancredi D.J. German J.B. Slupsky C.M. Ashwood P. Mills D.A. Smilowitz J.T. Angkustsiri K. Pilot study of probiotic/colostrum supplementation on gut function in children with autism and gastrointestinal symptoms. PLoS One 2019 14 1 e0210064 10.1371/journal.pone.0210064 30625189
    [Google Scholar]
  51. Gondalia S.V. Palombo E.A. Knowles S.R. Cox S.B. Meyer D. Austin D.W. Molecular characterisation of gastrointestinal microbiota of children with autism (with and without gastrointestinal dysfunction) and their neurotypical siblings. Autism Res. 2012 5 6 419 427 10.1002/aur.1253 22997101
    [Google Scholar]
  52. Acosta A.M. Chavez C.B. Flores J.T. Olotegui M.P. Pinedo S.R. Trigoso D.R. Vasquez A.O. Ahmed I. Alam D. Ali A. Bhutta Z.A. Qureshi S. Shakoor’ S. Soofi S. Turab A. Yousafzai A.K. Zaidi A.K.M. Bodhidatta L. Mason C.J. Babji S. Bose A. John S. Kang G. Kurien B. Muliyil J. Raghava M.V. Ramachandran A. Rose A. Pan W. Ambikapathi R. Carreon D. Charu V. Dabo L. Doan V. Graham J. Hoest C. Knobler S. Lang D. McCormick B. McGrath M. Miller M. Mohale A. Nayyar G. Psaki S. Rasmussen Z. Richard S. Seidman J. Wang V. Blank R. Gottlieb M. Tountas K. Amour C. Mduma E. Ahmed T. Ahmed A.M.S. Dinesh M. Tofail F. Haque R. Hossain I. Islam M. Mahfuz M. Chandyo R.K. Shrestha P.S. Shrestha R. Ulak M. Black R. Caulfield L. Checkley W. Chen P. Kosek M. Lee G. Yori P.P. Murray-Kolb L. Schaefer B. Pendergast L. Abreu C. Binda A. Costa H. Di Moura A. Filho J.Q. Leite A. Lima A. Lima N. Lima I. Maciel B. Moraes M. Mota F. Oria R. Quetz J. Soares A. Svensen E. Tor S. Patil C. Bessong P. Mahopo C. Mapula A. Nesamvuni C. Nyathi E. Samie A. Barrett L. Gratz J. Guerrant R. Houpt E. Olmsted L. Petri W. Platts-Mills J. Scharf R. Shrestha B. Shrestha S.K. The MAL-ED study: A multinational and multidisciplinary approach to understand the relationship between enteric pathogens, malnutrition, gut physiology, physical growth, cognitive development, and immune responses in infants and children up to 2 years of age in rearticle-title-poor environments. Clin. Infect. Dis. 2014 59 S193 S206 (Suppl. 4) 10.1093/cid/ciu653 25305287
    [Google Scholar]
  53. Mayer E.A. Gut feelings: The emerging biology of gut–brain communication. Nat. Rev. Neurosci. 2011 12 8 453 466 10.1038/nrn3071 21750565
    [Google Scholar]
  54. Hack M. Klein N.K. Taylor H.G. Long-term developmental outcomes of low birth weight infants. Future Child. 1995 5 1 176 196 10.2307/1602514 7543353
    [Google Scholar]
  55. Werling D.M. Geschwind D.H. Sex differences in autism spectrum disorders. Curr. Opin. Neurol. 2013 26 2 146 153 10.1097/WCO.0b013e32835ee548 23406909
    [Google Scholar]
  56. Bradley R.H. Corwyn R.F. Socioeconomic status and child development. Annu. Rev. Psychol. 2002 53 1 371 399 10.1146/annurev.psych.53.100901.135233 11752490
    [Google Scholar]
  57. Dominguez-Bello M.G. Costello E.K. Contreras M. Magris M. Hidalgo G. Fierer N. Knight R. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc. Natl. Acad. Sci. USA 2010 107 26 11971 11975 10.1073/pnas.1002601107 20566857
    [Google Scholar]
  58. Borre Y.E. Moloney R.D. Clarke G. Dinan T.G. Cryan J.F. The impact of microbiota on brain and behavior: Mechanisms & therapeutic potential. In: Microbial Endocrinology. The Microbiota-Gut-Brain Axis in Health and Disease 2014 Vol. 817 373 403 10.1007/978‑1‑4939‑0897‑4_17
    [Google Scholar]
  59. De Angelis M. Francavilla R. Piccolo M. De Giacomo A. Gobbetti M. Autism spectrum disorders and intestinal microbiota. Gut Microbes 2015 6 3 207 213 10.1080/19490976.2015.1035855 25835343
    [Google Scholar]
  60. Jung T.H. Hwang H.J. Han K.S. Correlation of attention deficit hyperactivity disorder with gut microbiota according to the dietary intake of Korean elementary school students. PLoS One 2022 17 9 e0275520 10.1371/journal.pone.0275520 36178961
    [Google Scholar]
  61. Jin C.J. Engstler A.J. Sellmann C. Ziegenhardt D. Landmann M. Kanuri G. Lounis H. Schröder M. Vetter W. Bergheim I. Sodium butyrate protects mice from the development of the early signs of non-alcoholic fatty liver disease: Role of melatonin and lipid peroxidation. Br. J. Nutr. 2016 116 10 1682 1693 10.1017/S0007114516004025 27876107
    [Google Scholar]
  62. Ameen A.O. Nielsen S.W. Kjær M.W. Andersen J.V. Westi E.W. Freude K.K. Aldana B.I. Metabolic preferences of astrocytes: Functional metabolic mapping reveals butyrate outcompetes acetate. J. Cereb. Blood Flow Metab. 2025 45 3 528 541 10.1177/0271678X241270457 39340267
    [Google Scholar]
  63. Maes M. Anderson G. Betancort Medina S.R. Seo M. Ojala J.O. Integrating autism spectrum disorder pathophysiology: Mitochondria, vitamin A, CD38, oxytocin, serotonin and melatonergic alterations in the placenta and gut. Curr. Pharm. Des. 2020 25 41 4405 4420 10.2174/1381612825666191102165459 31682209
    [Google Scholar]
  64. da Silveira Cruz-Machado S. Guissoni Campos L.M. Fadini C.C. Anderson G. Markus R.P. Pinato L. Disrupted nocturnal melatonin in autism: Association with tumor necrosis factor and sleep disturbances. J. Pineal Res. 2021 70 3 e12715 10.1111/jpi.12715 33421193
    [Google Scholar]
  65. de Souza A.L.D.M. Giacheti C.M. Do Couto M.C.H. Galina Spilla C.S. da Silva N.C. Proença M. Pinato L. Sleep disturbance in children with attention-deficit hyperactivity disorder: Relationship with melatonin and behavior. Neurol. Res. 2024 46 9 803 811 10.1080/01616412.2024.2359261 38832631
    [Google Scholar]
  66. Gevezova M. Sarafian V. Anderson G. Maes M. Inflammation and mitochondrial dysfunction in autism spectrum disorder. CNS Neurol. Disord. Drug Targets 2020 19 5 320 333 10.2174/1871527319666200628015039 32600237
    [Google Scholar]
  67. Seo M. Anderson G. Gut-amygdala interactions in autism spectrum disorders: Developmental roles via regulating mitochondria, exosomes, immunity and microRNAs. Curr. Pharm. Des. 2020 25 41 4344 4356 10.2174/1381612825666191105102545 31692435
    [Google Scholar]
  68. Anderson G. Betancort M.S.R. Autism spectrum disorders: Role of pre- and post-natal gammadelta (γδ) T cells and immune regulation. Curr. Pharm. Des. 2020 25 41 4321 4330 10.2174/1381612825666191102170125 31682211
    [Google Scholar]
  69. Volkova A. Ruggles K. Schulfer A. Gao Z. Ginsberg S.D. Blaser M.J. Effects of early-life penicillin exposure on the gut microbiome and frontal cortex and amygdala gene expression. iScience 2021 24 7 102797 10.1016/j.isci.2021.102797 34355145
    [Google Scholar]
  70. Silva Y.P. Bernardi A. Frozza R.L. The role of short-chain fatty acids from gut microbiota in gut-brain communication. Front. Endocrinol. 2020 11 25 25 10.3389/fendo.2020.00025 32082260
    [Google Scholar]
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