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Gut microbiota: PNEI director of developmental age

DOI
https://doi.org/10.3280/pnei2026oa23591
Submitted
agosto 31, 2026
Published
2026-09-30

Abstract

The epistemological transition of modern pediatrics is marked by the overcoming of the reductionist model in favor of a systemic and integrated vision of the human organism. In this scenario, Psychoneuroendocrinoimmunology (PNEI) offers the theoretical framework to understand how adult health is programmed during the very early stages of ontogenetic development (Bottaccioli, Bottaccioli, 2020), and the gut microbiota no longer represents a cluster of commensal microorganisms but a true dynamic, plastic, and systemic psychoneuroendocrinoimmunological organ, capable of acting as the undisputed director of the pathway (Lozupone et al., 2012). Through the use of omics sciences (metagenomics, transcriptomics, metabolomics), contemporary research has revealed the functional profile of this microbial ecosystem (Turnbaugh et al., 2009; Milani et al., 2017), demonstrating how its chemical metabolites integrate into the host’s regulatory networks. This article delves into the biochemical and molecular mechanisms through which the microbiota modulates the bidirectional communication axes between the gut, immune system, endocrine system, and central nervous system in the first 1000 days of life (Cryan et al., 2019).

References

  1. Arrieta M.C., Stiemsma L.T., Dimitriu P.A., Thorson L., Russell S., & Yurist-Doutsch S. (2015). Early infancy microbial dysbiosis is associated with increased risk of asthma. Science Translational Medicine, 2015;7(307):307ra152. Doi: 10.1126/scitranslmed.aab2271
  2. Bäckhed F., Roswall J., Peng Y., Feng Q., Jia H., & Kovatcheva-Datchary P. (2015). Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host & Microbe, 2015;17(5):690-703. Doi: 10.1016/j.chom.2015.04.004
  3. Barker D.J.P. (1998). Mothers, babies and health in later life. Edinburgh: Churchill Livingstone.
  4. Bass J., & Takahashi J.S. (2010). Circadian integration of metabolism and energetics. Science, 2010;330(6009):1349-1354. Doi: 10.1126/science.1195027
  5. Belkaid Y., & Hand T.W. (2014). Role of the microbiota in immunity and inflammation. Cell, 2014;157(1):121-141. Doi: 10.1016/j.cell.2014.03.011
  6. Bode L. (2012). Human milk oligosaccharides: Every baby needs a sugar mama. Glycobiology, 2012;22(9):1147-1162. Doi: 10.1093/glycob/cws074
  7. Bottaccioli F., & Bottaccioli A.G. (2020). Psiconeuroendocrinoimmunologia e scienza della cura integrata. Il manuale. Milano: Edra.
  8. Cani P.D., Amar J., Iglesias M.A., Poggi M., Knauf C., & Bastelica D. (2007). Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes, 2007;56(7):1761-1772. Doi: 10.2337/db06-1491
  9. Clarke G., Grenham S., Scully P., Fitzgerald P., Moloney R.D., & Shanahan F. (2013). The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Molecular Psychiatry, 2013;18(6):666-673. Doi: 10.1038/mp.2012.77.
  10. Codoñer-Franch P., & Gombert M. (2018). Circadian rhythms in the pathogenesis of gastrointestinal diseases. World journal of gastroenterology, 2018;24(38):4297-4303. Doi: 10.3748/wjg.v24.i38.4297
  11. Cryan J.F., O’Riordan K.J., Cowan C.S.M., Sandhu K.V., Bastiaanssen T.F.S., & Boehme M. (2019). The microbiota-gut-brain axis. Physiological reviews, 2019;99(4):1877-2013. Doi: 10.1152/physrev.00018.2018.
  12. De Vadder F., Kovatcheva-Datchary P., Goncalves D., Vinera M., Zitoun C., & Duchampt A. (2014). Microbiota-generated metabolites promote metabolic benefits via gut gluconeogenesis. Cell, 2014;156(1-2):84-96. Doi: 10.1016/j.cell.2013.12.016.
  13. Diaz Heijtz R., Wang S., Anuar F., Qian Y., Björkholm B., & Samuelsson A. (2011). Normal gut microbiota modulates brain development and behavior. Proceedings of the National Academy of Sciences of the United States of America, 2011;108(7):3047-3052. Doi: 10.1073/pnas.1010529108.
  14. Dominguez-Bello M.G., Costello E.K., Contreras M., Magris M., Hidalgo G., & Fierer N. (2010). Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proceedings of the National Academy of Sciences of the United States of America, 2010;107(26):11971-11975. Doi: 10.1073/pnas.1002601107
  15. Erny D., Angelis A.L., Jaitin D., Wieghofer P., Staszewski O., & David E. (2015). Host microbiota constantly control maturation and function of microglia in the CNS. Nature Neuroscience, 2015;18(7):965-977. Doi: 10.1038/nn.4030
  16. Foster J.A., Rinaman L., & Cryan J.F. (2017). Stress & the gut-brain axis: Regulation by the microbiome. Neurobiology of Stress, 7, 124–136. Doi: 10.1016/j.ynstr.2017.03.001
  17. Gensollen T., Iyer S.S., Kasper D.L., & Blumberg R.S. (2016). How colonization by microbiota in early life shapes the immune system. Science, 2016;352(6285):539-544. Doi: 10.1126/science.aad9378
  18. Gibson G.R., Hutkins R., Sanders M.E., Prescott S.L., Reimer R.A., & Salminen S. (2017). Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nature Reviews. Gastroenterology & Hepatology, 2017;14(8):491-502. Doi: 10.1038/nrgastro.2017.75
  19. Hill C., Guarner F., Reid G., Gibson G.R., Merenstein D.J., & Pot B. (2014). Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the scope and appropriate use of the term probiotic. Nature Reviews. Gastroenterology & Hepatology, 2014;11(8):506-514. Doi: 10.1038/nrgastro.2014.66
  20. Koenig J.E., Spor A., Scalfone N., Fricker A.D., Stombaugh J., & Knight R. (2011). Succession of microbial communities in the infant gut and its relation to formatting the adult community. Proceedings of the National Academy of Sciences of the United States of America, 1(Suppl 1), 4578–4585. Doi: 10.1073/pnas.1000081107
  21. Koh A., Vadder F., Kovatcheva-Datchary P., & Bäckhed F. (2016). From dietary fiber to host physiology: Short-chain fatty acids as key bacterial metabolites. Cell, 2016;165(6):1332-1345. Doi: 10.1016/j.cell.2016.05.041
  22. Lozupone C.A., Stombaugh J.I., Gordon J.I., Jansson J.K., & Knight R. (2012). Diversity, stability and resilience of the human gut microbiota. Nature, 2012;489(7415):220-230. Doi: 10.1038/nature11550.
  23. Milani C., Duranti S., Bottacini F., Casey E., Turroni F., & Mahony J. (2017). The first microbial colonizers of the human gut: Composition, activities, and health implications of the infant gut microbiota. Microbiology and Molecular Biology Reviews : MMBR, 2017;81(4):e00036-17. Doi: 10.1128/mmbr.00036-17
  24. Neu J., & Rushing J. (2011). Cesarean versus vaginal delivery: Long-term infant outcomes and the hygiene hypothesis. Clinics in Perinatology, 2011;38(2):321-331. Doi: 10.1016/j.clp.2011.03.008
  25. O’Mahony S.M., Marchesi S. JR, P C., C C., AM Q., & E.M.M. (2009). Early life stress alters behavior, immunity, and microbiota in rats: Implications for irritable bowel syndrome. Biological Psychiatry, 2009;65(3):263-267. Doi: 10.1016/j.biopsych.2008.06.026.
  26. Ridaura V.K., Faith J.J., Rey F.E., Cheng J., Duncan A.E., & Kau A.L. (2013). Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science, 2013;341(6150):1241214. Doi: 10.1126/science.1241214
  27. Round J.L., & Mazmanian S.K. (2009). The gut microbiota shapes intestinal immune responses during health and disease. Nature reviews. Immunology, 2009;9(5):313-323. Doi: 10.1038/nri2515
  28. Salminen S., Collado M.C., Endo A., Hill C., Lebeer S., & Quigley E.M.M. (2021). The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics. Nature Reviews. Gastroenterology & Hepatology, 2021;18(9):649-667. Doi: 10.1038/s41575-021-00440-6
  29. Sampson T.R., Debelius J.W., Thron T., Janssen S., Shastri G.G., & Ilhan Z.E. (2016). Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson’s disease. Cell, 2016;167(6):1469-1480. Doi: 10.1016/j.cell.2016.11.018
  30. Sharon G., Sampson T.R., Geschwind D.H., & Mazmanian S.K. (2016). The central nervous system and the gut microbiome. Cell, 2016;167(4):915-932. Doi: 10.1016/j.cell.2016.10.027
  31. Stilling R. M., Dinan T. G. & Cryan, J. F. (2014). Microbial genes, brain & behaviour—epigenetic regulation of the gut–brain axis. Genes, Brain and Behavior, 13(1), 69–86. Doi: 10.1111/gbb.12109.
  32. Subramanian S., Huq S., Yatsunenko T., Haque R., Mahfuz M., & Alam M.A. (2014). Persistent gut microbiota immaturity in malnourished Bangladeshi children. Nature, 2014;510(7505):417-421. Doi: 10.1038/nature13421.
  33. Sudo N., Chida Y., Aiba Y., Sonoda J., Oyama N., & Yu X.N. (2004). Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. The Journal of Physiology, 2004;558(Pt 1):263-275. Doi: 10.1113/jphysiol.2004.063388
  34. Tamburini S., Shen N., Wu H.C., & Clemente J.C. (2016). The microbiome in early life: Implications for health outcomes. Nature Medicine, 2016;22(7):713-722. Doi: 10.1038/nm.4142
  35. Turnbaugh P.J., Hamady M., Yatsunenko T., Cantarel B.L., Duncan A., & Ley R.E. (2009). A core gut microbiome in obese and lean twins. Nature, 2009;457(7228):480-484. Doi: 10.1038/nature07540
  36. Vuong H.E., Pronovost G.N., Williams D.W., Coley E.J.L., Siegler E.L., & Carey A. (2020). The maternal microbiome modulates fetal neurodevelopment in mice. Nature, 2020;586(7828):281-286. Doi: 10.1038/s41586-020-2745-3.
  37. Wopereis H., Oozeer R., Knipping K., Kraneveld A.D., & Garssen J. (2014). The first thousand days - intestinal microbiology of early life: Establishing a symbiosis. Pediatric Allergy and Immunology : Official Publication of the European Society of Pediatric Allergy and Immunology, 2014;25(5):428-438. Doi: 10.1111/pai.12232
  38. Yano J.M., Yu K., Donaldson G.P., Shastri G.G., Ann P., & Ma L. (2015). Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell, 2015;161(2):264-276. Doi: 10.1016/j.cell.2015.02.047