Preterm Birth by Cesarean Section: The Gut-Brain Axis, a Key Regulator of Brain Development

Understanding the long-term functional implications of gut microbial communities during the perinatal period is a bourgeoning area of research. Numerous studies have revealed the existence of a "gut-brain axis" and the impact of an alteration of gut microbiota composition in brain diseases. Recent research has highlighted how gut microbiota could affect brain development and behavior. Many factors in early life such as the mode of delivery or preterm birth could lead to disturbance in the assembly and maturation of gut microbiota. Notably, global rates of cesarean sections (C-sections) have increased in recent decades and remain important when considering premature delivery. Both preterm birth and C-sections are associated with an increased risk of neurodevelopmental disorders such as autism spectrum disorders; with neuroinflammation a major risk factor. In this review, we explore links between preterm birth by C-sections, gut microbiota alteration, and neuroinflammation. We also highlight C-sections as a risk factor for developmental disorders due to alterations in the microbiome.

[1]  M. Tremblay,et al.  The Outcomes of Maternal Immune Activation Induced with the Viral Mimetic Poly I:C on Microglia in Exposed Rodent Offspring , 2023, Developmental Neuroscience.

[2]  Peifeng Ji,et al.  Changes to gut amino acid transporters and microbiome associated with increased E/I ratio in Chd8+/− mouse model of ASD-like behavior , 2022, Nature Communications.

[3]  P. Gressens,et al.  miR‐146b Protects the Perinatal Brain against Microglia‐Induced Hypomyelination , 2021, Annals of neurology.

[4]  F. Zhao,et al.  Deterministic transition of enterotypes shapes the infant gut microbiome at an early age , 2021, Genome Biology.

[5]  J. Hajnal,et al.  Development of human white matter pathways in utero over the second and third trimester , 2021, Proceedings of the National Academy of Sciences.

[6]  R. Geha,et al.  Multi-kingdom ecological drivers of microbiota assembly in preterm infants , 2021, Nature.

[7]  Yen-Wenn Liu,et al.  Dysbiotic Gut Microbiota and Dysregulation of Cytokine Profile in Children and Teens With Autism Spectrum Disorder , 2021, Frontiers in Neuroscience.

[8]  Cassandra Willyard How gut microbes could drive brain disorders , 2021, Nature.

[9]  M. Yassour,et al.  Lessons learned from the prenatal microbiome controversy , 2021, Microbiome.

[10]  A. Franks,et al.  A pioneer calf foetus microbiome , 2020, Scientific Reports.

[11]  M. Prinz,et al.  How microbiota shape microglial phenotypes and epigenetics , 2020, Glia.

[12]  V. Arija,et al.  Composition of Gut Microbiota in Children with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis , 2020, Nutrients.

[13]  C. Power,et al.  Bacterial Peptidoglycan as a Driver of Chronic Brain Inflammation. , 2020, Trends in molecular medicine.

[14]  W. L. Lim,et al.  Antidepressive Mechanisms of Probiotics and Their Therapeutic Potential , 2020, Frontiers in Neuroscience.

[15]  B. Pereira,et al.  Association of Maternal Weight and Gestational Weight Gain with Maternal and Neonate Outcomes: A Prospective Cohort Study , 2019, Journal of clinical medicine.

[16]  T. Dinan,et al.  Gut Microbiota: A Perspective for Psychiatrists , 2019, Neuropsychobiology.

[17]  E. Petretto,et al.  Decreased microglial Wnt/β-catenin signalling drives microglial pro-inflammatory activation in the developing brain. , 2019, Brain : a journal of neurology.

[18]  R. Mori,et al.  Mode of delivery and pregnancy outcomes in preterm birth: a secondary analysis of the WHO Global and Multi-country Surveys , 2019, Scientific Reports.

[19]  G. Réus,et al.  Gut microbiota–brain axis in depression: The role of neuroinflammation , 2019, The European journal of neuroscience.

[20]  K. Ikeda,et al.  Different impacts on brain function depending on the mode of delivery , 2019, Brain Research.

[21]  Kieran Rea,et al.  The Microbiota-Gut-Brain Axis. , 2019, Physiological reviews.

[22]  S. Lippmann,et al.  Gut microbiota and health , 2019, Postgraduate medicine.

[23]  J. Swann,et al.  Editorial overview: CNS diseases and the microbiome. , 2019, Current opinion in pharmacology.

[24]  D. Charnock-Jones,et al.  Human placenta has no microbiome but can harbour potential pathogens , 2019, Nature.

[25]  A. Edwards,et al.  Interneuron Development Is Disrupted in Preterm Brains With Diffuse White Matter Injury: Observations in Mouse and Human , 2019, Front. Physiol..

[26]  P. Crack,et al.  The influence of neuroinflammation in Autism Spectrum Disorder , 2019, Brain, Behavior, and Immunity.

[27]  Y. Ben-Ari,et al.  Term or Preterm Cesarean Section Delivery Does Not Lead to Long-term Detrimental Consequences in Mice. , 2019, Cerebral cortex.

[28]  Young-Mo Kim,et al.  Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice , 2019, Cell.

[29]  F. Tao,et al.  Elective caesarean delivery and offspring’s cognitive impairment: Implications of methylation alteration in hippocampus glucocorticoid signaling genes , 2019, Brain Research Bulletin.

[30]  E. Claud,et al.  Connection between gut microbiome and brain development in preterm infants. , 2018, Developmental psychobiology.

[31]  A. Castillo-Ruiz,et al.  Birth delivery mode alters perinatal cell death in the mouse brain , 2018, Proceedings of the National Academy of Sciences.

[32]  P. Gressens,et al.  Neuroinflammation in preterm babies and autism spectrum disorders , 2018, Pediatric Research.

[33]  Yifei Wang,et al.  The Gut-Microglia Connection: Implications for Central Nervous System Diseases , 2018, Front. Immunol..

[34]  S. Peddada,et al.  Preterm infants have distinct microbiomes not explained by mode of delivery, breastfeeding duration or antibiotic exposure. , 2018, International journal of epidemiology.

[35]  Ceymi Doenyas Gut Microbiota, Inflammation, and Probiotics on Neural Development in Autism Spectrum Disorder , 2018, Neuroscience.

[36]  K. Korpela,et al.  Intestinal microbiota development and gestational age in preterm neonates , 2018, Scientific Reports.

[37]  D. Rowitch,et al.  Reactive astrocyte COX2‐PGE2 production inhibits oligodendrocyte maturation in neonatal white matter injury , 2017, Glia.

[38]  Enrico Petretto,et al.  Integrative genomics of microglia implicates DLG4 (PSD95) in the white matter development of preterm infants , 2017, Nature Communications.

[39]  M. Bozkurt,et al.  Platelet-to-lymphocyte ratio: A new inflammatory marker for the diagnosis of preterm premature rupture of membranes , 2017, Journal of the Turkish German Gynecological Association.

[40]  R. Loos,et al.  The prenatal gut microbiome: are we colonized with bacteria in utero? , 2017, Pediatric obesity.

[41]  M. Underwood,et al.  The Microbiota of the Extremely Preterm Infant , 2017, Clinics in Perinatology.

[42]  I. Hertz-Picciotto,et al.  Neonatal Cytokine Profiles Associated With Autism Spectrum Disorder , 2017, Biological Psychiatry.

[43]  A. Guastella,et al.  The Immune System, Cytokines, and Biomarkers in Autism Spectrum Disorder , 2017, Neuroscience Bulletin.

[44]  M. Gissler,et al.  Caesarean section and risk of autism across gestational age: a multi-national cohort study of 5 million births. , 2016, International journal of epidemiology.

[45]  R. Ristl,et al.  Effect of delivery mode on neonatal outcome among preterm infants: an observational study , 2016, Wiener klinische Wochenschrift.

[46]  H. Forssberg,et al.  The bacterial peptidoglycan-sensing molecule Pglyrp2 modulates brain development and behavior , 2016, Molecular Psychiatry.

[47]  T. Dinan,et al.  Transferring the blues: Depression-associated gut microbiota induces neurobehavioural changes in the rat. , 2016, Journal of psychiatric research.

[48]  J Licinio,et al.  Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host’s metabolism , 2016, Molecular Psychiatry.

[49]  T. Dinan,et al.  Regulation of prefrontal cortex myelination by the microbiota , 2016, Translational Psychiatry.

[50]  I. Amit,et al.  Host microbiota constantly control maturation and function of microglia in the CNS , 2015, Nature Neuroscience.

[51]  P. Kearney,et al.  Research review: Birth by caesarean section and development of autism spectrum disorder and attention-deficit/hyperactivity disorder: a systematic review and meta-analysis. , 2015, Journal of child psychology and psychiatry, and allied disciplines.

[52]  Rustem F. Ismagilov,et al.  Indigenous Bacteria from the Gut Microbiota Regulate Host Serotonin Biosynthesis , 2015, Cell.

[53]  B. Branger,et al.  Survival and morbidity of preterm children born at 22 through 34 weeks' gestation in France in 2011: results of the EPIPAGE-2 cohort study. , 2015, JAMA pediatrics.

[54]  K. Bønnelykke,et al.  Cesarean Section and Chronic Immune Disorders , 2015, Pediatrics.

[55]  Cathleen K. Yoshida,et al.  Neonatal cytokines and chemokines and risk of Autism Spectrum Disorder: the Early Markers for Autism (EMA) study: a case-control study , 2014, Journal of Neuroinflammation.

[56]  L. Kasper,et al.  The role of microbiome in central nervous system disorders , 2014, Brain, Behavior, and Immunity.

[57]  J. Petrosino,et al.  Microbiota Modulate Behavioral and Physiological Abnormalities Associated with Neurodevelopmental Disorders , 2013, Cell.

[58]  L. Desbonnet,et al.  Microbiota is essential for social development in the mouse , 2013, Molecular Psychiatry.

[59]  Myron Sasser,et al.  Hypothesis for a systems connectivity model of Autism Spectrum Disorder pathogenesis: links to gut bacteria, oxidative stress, and intestinal permeability. , 2013, Medical hypotheses.

[60]  R. Dziarski,et al.  Peptidoglycan recognition proteins: modulators of the microbiome and inflammation , 2011, Nature Reviews Immunology.

[61]  Scott M. Williams,et al.  An integrated systems biology approach to the study of preterm birth using "-omic" technology - a guideline for research , 2011, BMC pregnancy and childbirth.

[62]  K. McCoy,et al.  The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. , 2011, Gastroenterology.

[63]  H. Forssberg,et al.  Normal gut microbiota modulates brain development and behavior , 2011, Proceedings of the National Academy of Sciences.

[64]  L. T. Angenent,et al.  Succession of microbial consortia in the developing infant gut microbiome , 2010, Proceedings of the National Academy of Sciences.

[65]  R. Knight,et al.  Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns , 2010, Proceedings of the National Academy of Sciences.

[66]  R. Gaykema,et al.  Campylobacter jejuni infection increases anxiety-like behavior in the holeboard: Possible anatomical substrates for viscerosensory modulation of exploratory behavior , 2008, Brain, Behavior, and Immunity.

[67]  J. W. Rudy,et al.  Neonatal infection induces memory impairments following an immune challenge in adulthood. , 2005, Behavioral neuroscience.

[68]  Y. Chida,et al.  Postnatal microbial colonization programs the hypothalamic–pituitary–adrenal system for stress response in mice , 2004, The Journal of physiology.

[69]  J. Moutquin Classification and heterogeneity of preterm birth , 2003, BJOG : an international journal of obstetrics and gynaecology.

[70]  M. Dombrowski,et al.  The Preterm Prediction Study: prediction of preterm premature rupture of membranes through clinical findings and ancillary testing. The National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. , 2000, American journal of obstetrics and gynecology.

[71]  R. Diaz Heijtz Fetal, neonatal, and infant microbiome: Perturbations and subsequent effects on brain development and behavior. , 2016, Seminars in fetal & neonatal medicine.

[72]  V. Tremaroli,et al.  Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life. , 2015, Cell host & microbe.