Review ArticleGut Microbiota: The Conductor in the Orchestra of Immune–Neuroendocrine Communication
Introduction
Our knowledge of the host–microbe interrelationship is accelerating because of the availability of rapidly expanding molecular techniques, especially in combination with the use of reductionist in vivo host models. A growing body of research continues to show that the normal mammalian structure and function are significantly dependent on their constant engagement in complex interactions with microbes.1 For example, the intestinal microbiota with its components and metabolites affects the host physiology in various ways to control energy homeostasis, gut barrier function, mucosal inflammation, and behavior.2, 3, 4 Subsequently, the host modifies many of the microbial activities, which suggests a feedback mechanism that could influence the microbiota and drive a further cycle of biological changes to host physiology.5 This multidirectional interactive dialogue seems to strongly influence an expanding repertoire of human disorders, including obesity, depression, and irritable bowel syndrome; the goal is to decipher the tête-à-tête between the host and its commensal organisms.6, 7
The present review highlights emerging evidence, which provides a framework for appreciating the impact of the host–microbiota interplay on health that is undoubtedly much broader than previously thought. This review outlines the impact of the gut microbiota on the immune system as well as the neuroendocrine system, both of which point to a potential role of the microbiota as crucial coordinators in the cross-talk between these systems.
Section snippets
Materials and Methods
Literature from a range of sources, including PubMed, Google Scholar, and MEDLINE, was searched to identify recent reports on the impact of the gut microbiota on the host immune and neuroendocrine systems in health and disease. All data were gathered for the latest available years.
The Host–Microbiota Dialogue
Over the past decade, remarkable advances toward a better understanding of how the host–microbe interactome is linked with most pathways that affect health, disease, and aging were made possible with novel technologies; these include high-throughput DNA sequencing, bioinformatics, and gnotobiotic animal models.1 The intimate interactions between the host and its microbes that outnumber the host’s cells by 10 to 1 are required to stimulate the complete maturation of an efficient intestinal
Conclusions
Over the past decade, preclinical trials, as well as a few clinical studies, have highlighted the crucial role of the gut microbiota in maintaining host homeostasis. Analogously, microbiota dysbiosis has been associated with a wide range of host disorders, including inflammatory bowel disorders, neuroendocrine disorders, and behavioral disorders. This growing body of research illustrates the significant direct effect that microbes have on the host immune and neuroendocrine systems. Nonetheless,
Conflicts of Interest
The authors’ research at the Alimentary Pharmabiotic Centre is funded by Science Foundation Ireland, through the Irish Government’s National Development Plan in collaboration with a variety of pharmaceutical and food industries. The authors have indicated that they have no other conflicts of interest regarding the content of this article.
Acknowledgments
Drs. Dinan and Cryan are supported by Science Foundation Ireland (grant no. 07/CE/B1368 and 12/RC/2273) and by the Irish Health Research Board, Health Research Awards (HRA_POR/2011/23) and (HRA_POR/2012/32). Sahar El Aidy contribution: literature search, figure creation, writing. Timothy G. Dinan and John Cryan: critical reviewing.
References (122)
Specialized metabolites from the microbiome in health and disease
Cell Metab
(2014)- et al.
Microbial determinants of biochemical individuality and their impact on toxicology and pharmacology
Cell Metab
(2014) The infant microbiome development: mom matters
Trends Mol Med
(2015)Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences
Cell
(2014)Microbiota and neurodevelopmental windows: implications for brain disorders
Trends Mol Med
(2014)Gut immune maturation depends on colonization with a host-specific microbiota
Cell
(2012)- et al.
Defective antigen-presenting cell function in human neonates
Clin Immunol
(2006) Temporal and spatial interplay of microbiota and intestinal mucosa drive establishment of immune homeostasis in conventionalized mice
Mucosal Immunol
(2012)An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system
Cell
(2005)The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses
Immunity
(2009)
Can we vaccinate against depression?
Drug Discov Today
Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders
Cell
Toll-like receptors are key players in neurodegeneration
Int Immunopharmacol
Antidepressant-like effects of the histone deacetylase inhibitor, sodium butyrate, in the mouse
Biol Psychiatry
Effects of the histone deacetylase inhibitor sodium butyrate in models of depression and anxiety
Neuropharmacology
Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine
Cell Host Microbe
Serotonin, tryptophan metabolism and the brain-gut-microbiome axis
Behav Brain Res
Physiological responses of guinea-pig myenteric neurons secondary to the release of endogenous serotonin by tryptamine
Neuroscience
Psychobiotics: a novel class of psychotropic
Biol Psychiatry
The microbiome revolution
J Clin Invest
Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour
Nat Rev Neurosci
Functional interactions between the gut microbiota and host metabolism
Nature
Interactions between the microbiota and the immune system
Science
The human microbiome: opportunities and challenges for clinical care
Intern Med J
The human gut microbiome: ecology and recent evolutionary changes
Annu Rev Microbiol
Diversity of the human intestinal microbial flora
Science
A human gut microbial gene catalogue established by metagenomic sequencing
Nature
Human nutrition, the gut microbiome and the immune system
Nature
Food, immunity, and the microbiome
Gastroenterology
Staphylococcus epidermidis: a differential trait of the fecal microbiota of breast-fed infants
BMC Microbiol
Development of the human infant intestinal microbiota
PLoS Biol
Intestinal microbiota during early life—impact on health and disease
Proc Nutr Soc
Factors influencing the composition of the intestinal microbiota in early infancy
Pediatrics
The human microbiome and its potential importance to pediatrics
Pediatrics
Gut microbiota composition correlates with diet and health in the elderly
Nature
Intestinal colonization: how key microbial players become established in this dynamic process: microbial metabolic activities and the interplay between the host and microbes
Bioessays
Therapeutic modulation of microbiota-host metabolic interactions
Sci Transl Med
Microbiota, disease, and back to health: a metastable journey
Sci Transl Med
Immune adaptations that maintain homeostasis with the intestinal microbiota
Nat Rev Immunol
Bifidobacterium animalis subsp. lactis fermented milk product reduces inflammation by altering a niche for colitogenic microbes
Proc Natl Acad Sci U S A
Deciphering the tete-a-tete between the microbiota and the immune system
J Clin Invest
Exploring host-microbiota interactions in animal models and humans
Genes Dev
Protection of the neonate by the innate immune system of developing gut and of human milk
Pediatr Res
Imbalanced cytokine secretion in newborns
Biol Neonate
Transient hypogammaglobulinemia and unclassified hypogammaglobulinemia: ‘similarities and differences’
Pediatr Allergy Immunol
Commensal microbiota and CD8+ T cells shape the formation of invariant NKT cells
J Immunol
Macrophages in the small intestinal muscularis externa of embryos, newborn and adult germ-free mice
J Mol Histol
Immune responses that adapt the intestinal mucosa to commensal intestinal bacteria
Immunology
Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut
Nat Med
The gut microbiota elicits a profound metabolic reorientation in the mouse jejunal mucosa during conventionalisation
Gut
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