Microbes, immunity, and behavior: psychoneuroimmunology meets the microbiome
Open accessAbstract
There is now a large volume of evidence to support the view that the immune system is a key communication pathway between the gut and brain, which plays an important role in stress-related psychopathologies and thus provides a potentially fruitful target for psychotropic intervention. The gut microbiota is a complex ecosystem with a diverse range of organisms and a sophisticated genomic structure. Bacteria within the gut are estimated to weigh in excess of 1 kg in the adult human and the microbes within not only produce antimicrobial peptides, short chain fatty acids, and vitamins, but also most of the common neurotransmitters found in the human brain. That the microbial content of the gut plays a key role in immune development is now beyond doubt. Early disruption of the host-microbe interplay can have lifelong consequences, not just in terms of intestinal function but in distal organs including the brain. It is clear that the immune system and nervous system are in continuous communication in order to maintain a state of homeostasis. Significant gaps in knowledge remain about the effect of the gut microbiota in coordinating the immune-nervous systems dialogue. However, studies using germ-free animals, infective models, prebiotics, probiotics, and antibiotics have increased our understanding of the interplay. Early life stress can have a lifelong impact on the microbial content of the intestine and permanently alter immune functioning. That early life stress can also impact adult psychopathology has long been appreciated in psychiatry. The challenge now is to fully decipher the molecular mechanisms that link the gut microbiota, immune, and central nervous systems in a network of communication that impacts behavior patterns and psychopathology, to eventually translate these findings to the human situation both in health and disease. Even at this juncture, there is evidence to pinpoint key sites of communication where gut microbial interventions either with drugs or diet or perhaps fecal microbiota transplantation may positively impact mental health.
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ELS/CT may affect the signaling of the MGB axis in a major fashion and alter not only immune, but also CNS and stress system functioning with lifelong emotional and behavioral consequences (i.e., higher risk of neurodevelopmental disorders).
“As the microbiome plays an important role in the programming of the HPA axis and stress reactivity (244), ELS/CT may affect the signaling of the MGB axis in a major fashion and alter not only immune, but also CNS and stress system functioning with lifelong emotional and behavioral consequences (i.e., higher risk of neurodevelopmental disorders) (223, 239, 241, 245, 246).”
From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [239]
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Experimental — accuracy not yet measuredThe underrepresentation of infections and psychiatric disorders in animal studies may relate to differences in immune status, microbial exposure, and the scopes of behavioral assessments between animals and humans.
“which may relate to differences in immune status, microbial exposure, and the scopes of behavioral assessments between animals and humans (Dinan and Cryan, 2017; Huggins et al., 2019; Burger et al., 2023).”
From A large-scale concordance study of toxicity findings across preclinical species and humans for small molecules and biologics (2026) · cites this paper as Dinan and Cryan, 2017
The Future Research Directions section says that complex human gut microbial ecosystems are difficult to mimic and that translational investigations lag behind preclinical studies. It does not say that infections and psychiatric disorders are underrepresented in animal studies, or attribute such underrepresentation to differences in immune status, microbial exposure, or the scope of behavioral assessments. No page numbers are available in our copy. (LLM, conf=0.76)
Experimental — accuracy not yet measuredRecent data support a key role of gut microbiota and corresponding microbiota-derived PAMPs in central nervous processes like mood, cognition, pain, and eating behavior in animals, with first evidence for such a relationship in humans.
“recent data support a key role of gut microbiota and corresponding microbiota-derived PAMPs in central nervous processes like mood, cognition, pain, and eating behavior in animals, and there is also first evidence for such a relationship in humans (85, 150, 151, 394).”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [151]
Gaps in the current literature point to a dearth of longitudinal neurodevelopmental studies of children exposed to perinatal mental illness, with or without maternal use of psychotropics during pregnancy; few longitudinal studies to determine the mediating and moderating mechanisms through which PND exerts lasting effects on the child; and scant translational research on the potential role of the
“Gaps in the current literature point to a dearth of longitudinal neurodevelopmental studies of children exposed to perinatal mental illness, with or without maternal use of psychotropics during pregnancy; few longitudinal studies to determine the mediating and moderating mechanisms through which PND exerts lasting effects on the child; and scant translational research on the potential role of the”
From Perinatal Depression: Challenges and Opportunities (2021) · cites this paper as [33]
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References 198 · Cited by 246
Research works printed but not linked: 1
- [156]156. Sanders ME (1997). Overview of functional foods: emphasis on probiotic bacteria. In: Symposium on Functional Foods-Designer Foods for the Future. Elsevier Sci Ltd: Cork, Ireland.
- Authors
- Dinan, T. G., & Cryan, J. F.
- Affiliations
- University College Cork (IE)
- Venue
- Neuropsychopharmacology
- Published
- 2016-06-20
- Volume
- 42
- Issue
- 1
- Pages
- 178-192
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC5143479
- OpenAlex
- W2475333539
- Semantic Scholar
- c054e5b1b570b7379c2c0508ec730f37821f7b0c
- Cited by
- 246
- References
- 198
- Citations by year
- 2026: 5 · 2025: 25 · 2024: 29 · 2023: 29 · 2022: 25 · 2021: 28 · 2020: 35 · 2019: 23 · 2018: 21 · 2017: 22 · 2016: 4
- FWCI
- 2.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Mead Johnson Nutrition
- Danone
- Health Research Board (HRA_POR/2011/23, HRA_POR/2012/32, FP7/2007-2013)
- Science Foundation Ireland (SFI/12/RC/, 12/RC/2273, HRA_POR/2011/23, 12/RC/, SFI/12/RC/2273.)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- gut microbiota, gut-brain axis, psychoneuroimmunology, immune system, stress-related psychopathology, early life stress, probiotics, prebiotics, antibiotics, germ-free animals, fecal microbiota transplantation, neurotransmitters, short-chain fatty acids, antimicrobial peptides, mental health
- MeSH terms
- Gastrointestinal Microbiome, Animals, Mental Disorders, Brain, Humans, Immune System, Inflammation, Psychoneuroimmunology
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