John F Cryan

John F Cryan
University College Cork | UCC · Department of Anatomy and Neuroscience

Ph.D.

About

855
Publications
342,485
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66,141
Citations
Additional affiliations
January 2006 - December 2013
University College Cork
January 2003 - present

Publications

Publications (855)
Article
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A consequence of our progressively ageing global population is the increasing prevalence of worldwide age-related cognitive decline and dementia. In the absence of effective therapeutic interventions, identifying risk factors associated with cognitive decline becomes increasingly vital. Novel perspectives suggest that a dynamic bidirectional commun...
Article
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Irritable bowel syndrome (IBS) is a gut-brain disorder of multifactorial origin. Evidence of disturbed serotonergic function in IBS accumulated for the 5-HT3 receptor family. 5-HT3Rs are encoded by HTR3 genes and control GI function, and peristalsis and secretion, in particular. Moreover, 5-HT3R antagonists are beneficial in the treatment of diarrh...
Article
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Purpose of review: Diet is an essential modulator of the microbiota-gut-brain communication in health and disease. Consequently, diet-induced microbiome states can impact brain health and behaviour. The integration of microbiome into clinical nutrition perspectives of brain health is sparse. This review will thus focus on emerging evidence of micr...
Article
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Stress-related psychiatric disorders such as depression are among the leading causes of morbidity and mortality. Considering that many individuals fail to respond to currently available antidepressant drugs, there is a need for antidepressants with novel mechanisms. Polymorphisms in the gene encoding FK506-binding protein 51 (FKBP51), a co-chaperon...
Article
Scope: Milk fat globule membrane (MFGM) is an essential component of milk. Bovine MFGM (bMFGM) has been shown to support cognitive development and increase relative concentrations of serum phospholipids. This study investigated bioavailability of bMFGM components after oral administration in two preclinical models to explore whether dietary bMFGM...
Article
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Activated ghrelin receptor GHS-R1α triggers cell signalling pathways that modulate energy homeostasis and biosynthetic processes. However, the effects of ghrelin on mRNA translation are unknown. Using various reporter assays, here we demonstrate a rapid elevation of protein synthesis in cells within 15–30 min upon stimulation of GHS-R1α by ghrelin....
Article
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterised by deficits in social behaviour, increased repetitive behaviour, anxiety and gastrointestinal symptoms. The aetiology of ASD is complex and involves an interplay of genetic and environmental factors. Emerging pre-clinical and clinical studies have documented a potential r...
Article
Microbiome-to-nervous-system interactions are gaining much attention in fields that study health and disease, and diet is considered to be a key mediator in this communication. In a recent issue of Nature, Serger et al. show that, following nerve crush injury, intermittent fasting improves axonal regeneration through increased production of the mic...
Article
Background: Depression currently affects 4.4% of the global population, and 93.7% of this population suffer from major depressive disorder (MDD) according to 2017 statistics. MDD patients are more likely to suffer from co-morbidities such as cardiovascular disease and high body mass index (BMI), thus contributing to its large cost to society. Throu...
Article
Background and Aim Relative to men, women present with pain conditions more commonly. Although consistent differences exist between men and women in terms of physiological pain sensitivity, the underlying mechanisms are incompletely understood and yet could inform the development of effective sex specific treatments for pain. The gut microbiota can...
Preprint
Background Mental disorders, including major depressive disorder (MDD), are a leading cause of non-fatal burden of disease globally. Current conventional treatments for depression have significant limitations, and there have been few new treatments in decades. The microbiota-gut-brain- axis is now recognised as playing a role in mental and brain he...
Article
Sepsis Associated Encephalopathy, occurs in 70% of severe septic cases, following which survivors exhibit long-term cognitive impairment or global loss of cognitive function. Currently there is no clearly defined neurochemical basis of septic encephalopathy. Moreover, the lingering neurological complications associated with the severe acute respira...
Article
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Background There is emerging evidence that the gut microbiome composition is associated with several human health outcomes, which include cognitive performance. However, only a few prospective epidemiological studies exist and none among young adults. Here we address the gap in the literature by investigating whether the gut microbiome composition...
Article
Background: Depression currently affects 4.4% of the global population, and 93.7% of this population suffer from major depressive disorder (MDD) according to 2017 statistics. MDD patients are more likely to suffer from co-morbidities such as cardiovascular disease and high body mass index (BMI), thus contributing to its large cost to society. Throu...
Article
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The modulation of host and dietary metabolites by gut microbiota (GM) is important for maintaining correct host physiology and in the onset of various pathologies. An ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry method was developed for the targeted quantitation in human plasma, serum, and urine of 89...
Article
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Objective: An altered gut microbiota has been associated with insulin resistance, a metabolic dysfunction consisting of cellular insulin signaling impairment. The aim of the present study is to determine the taxonomic and functional fecal microbiota signatures associated with HOMA-IR index in a population with high cardiovascular risk. Methods:...
Article
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The blood-brain barrier (BBB) is vital for maintaining brain homeostasis by enabling an exquisite control of exchange of compounds between the blood and the brain parenchyma. Moreover, the BBB prevents unwanted toxins and pathogens from entering the brain. This barrier, however, breaks down with age and further disruption is a hallmark of many age-...
Article
In this issue of Cell Host & Microbe, Li et al. take a step toward a better understanding of the microbiome-gut-brain axis in mental health. They report gastrointestinal testosterone degradation by a specific bacterial strain as a potential mechanism impacting symptom expression in males with depression.
Article
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Nutritional approaches have emerged over the past number of years as suitable interventions to ameliorate the enduring effects of early life stress. Maternal separation (MS) is a rodent model of early life stress which induces widespread changes across the microbiota-gut-brain axis. Milk fat globule membrane (MFGM) is a neuroactive membrane structu...
Article
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Depression is considered a major public health concern, where existing pharmacological treatments are not equally effective across all patients. The pathogenesis of depression involves the interaction of complex biological components such as the immune system and the microbiota‐gut‐brain axis. Adjunctive lifestyle‐oriented approaches for depression...
Chapter
Neurodegenerative diseases are characterised by a progressive loss of neurons that leads to a range of cognitive and/or motor dysfunctions. During recent decades, some common pathways leading to neurodegeneration have been identified, such as protein misfolding, neuroinflammation, and the dysfunction of mitochondria and protein clearance systems. M...
Article
There has been a significant increase in Caesarean section (C-section) births worldwide over the past two decades and although it is can be a life-saving procedure, the enduring effects on host physiology are now undergoing further scrutiny. Indeed, epidemiological data have linked C-section birth with multiple immune, metabolic and neuropsychiatri...
Article
The role of the intestinal microbiota as a regulator of gut-brain axis signalling has risen to prominence in recent years. Understanding the relationship between the gut microbiota, the metabolites it produces, and the brain will be critical for the subsequent development of new therapeutic approaches, including the identification of novel psychobi...
Article
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Exposure to repeated social stress may cause maladaptive emotional reactions that can be reduced by healthy nutritional supplementation. Histaminergic neurotransmission has a central role in orchestrating specific behavioural responses depending on the homeostatic state of a subject, but it remains to be established if it participates in the protec...
Chapter
The gut microbiota is now well recognized as a key component in regulating various human processes, including metabolism, cardiovascular system, immunity, as well as brain and cognitive function. Diet has emerged as a main contributor to the microbiota composition and functional capacity; as such, increasing research is also now deciphering the foo...
Article
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The bed nucleus of the stria terminalis (BNST) is a focal point for the convergence of inputs from canonical stress-sensitive structures to fine-tune the response to stress. However, its role in mediating phenotypes of stress resilience or susceptibility is yet to be fully defined. In this study, we carried out unbiased RNA-sequencing to analyse th...
Article
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Scope: Increasing scientific evidence is validating the use of dietary strategies to support and improve brain health throughout the lifespan, with tailored nutritional interventions catering for specific life stages. Dietary phospholipid supplementations in early life and adulthood have been shown to alleviate some of the behavioural consequences...
Article
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Birth by Caesarean-section (C-section), which increases the risk for metabolic and immune disorders, disrupts the normal initial microbial colonisation of the gut, in addition to preventing early priming of the stress and immune-system priming. Animal studies have shown there are enduring psychological processes in C-section born mice. However, the...
Article
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Purpose of review: The gut microbiota has emerged as a key conduit in mental health and is a promising target for interventions. This review provides an update on recent advances in using microbiota-targeted approaches for the management of mental health. Recent findings: Approaches that have emerged as microbiota-targeted interventions in the m...
Article
Despite extensive evidence implicating the microbiota in regulating the immune system, the precise mechanisms underlying microbial control of microglial maturation remain unclear. In a methodological tour de force, Erny et al. (2021) identify acetate as an essential microbiota-derived molecule driving microglial metabolic pathways and functions dur...
Article
Background The tryptophan-kynurenine pathway is of major interest in psychiatry and is altered in patients with depression, schizophrenia and panic disorder. Stress and immune alterations can impact this system, through cortisol- and cytokine-induced activation. In addition, there is emerging evidence that the kynurenine pathway is associated with...
Article
Huntington's disease (HD) is a neurodegenerative disorder caused by a mutation in the huntingtin (HTT) gene, leading to a toxic version of the HTT protein. There are currently no disease-modifying therapies available. In this scenario, gene-based treatments for HD aimed at lowering HTT levels have become one of the most promising emerging therapeut...
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The particularly interdisciplinary nature of human microbiome research makes the organization and reporting of results spanning epidemiology, biology, bioinformatics, translational medicine and statistics a challenge. Commonly used reporting guidelines for observational or genetic epidemiology studies lack key features specific to microbiome studie...
Article
Changes in the microbiota are associated with alterations in nervous system structure-function and behavior and have been implicated in the etiology of neuropsychiatric and neurodegenerative disorders. Most of these studies have centered on mammalian models due to their phylogenetic proximity to humans. Indeed, the germ-free mouse has been a partic...
Article
Accumulating evidence suggests that the hippocampus is functionally segregated along its longitudinal axis into a dorsal (dHi) sub-region, shown to play roles in learning & memory and a ventral sub-region (vHi), involved anxiety and antidepressant action. Recent studies also suggest that the intermediate hippocampus (iHi) might be functionally inde...
Article
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The global public health crisis caused by COVID-19 has lasted longer than many of us would have hoped and expected. With its high uncertainty and limited control, the COVID-19 pandemic has undoubtedly asked a lot from all of us. One important central question is: how resilient have we proved in face of the unprecedented and prolonged coronavirus pa...
Article
Stress during critical periods of neurodevelopment is associated with an increased risk of developing stress-related psychiatric disorders which are more common in women than men. Hippocampal neurogenesis (the birth of new neurons) is vulnerable to maternal separation and inflammatory stressors, and emerging evidence suggests that hippocampal neuro...
Article
Background: Gut and oral microbiota are intrinsically linked to human health. Recent studies suggest a direct link with mental health through bidirectional gut–brain pathways. Emerging evidence suggests that the composition and/or function of intestinal microbiome differs in those with psychosis and schizophrenia as compared with controls. There is...
Article
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Fecal microbiota transplant (FMT) is a powerful tool used to connect changes in gut microbial composition with a variety of disease states and pathologies. While FMT enables potential causal relationships to be identified, the experimental details reported in preclinical FMT protocols are highly inconsistent and/or incomplete. This limitation refle...
Article
Aims: The novel coronavirus pandemic (COVID-19) has impacted the lives of people worldwide since March 2020. Social restrictions aimed at flattening the curve may be associated with an increase in mental health problems and have raised concerns regarding their effect on alcohol consumption. The objective of this study was to characterize changes in...
Chapter
The rapidly growing field of immunopsychiatry combines expertise and insights from immunology, psychiatry and neuroscience to understand the role of inflammation and other immune processes in causing and treating mental illness. This represents a major shift in mental health science, traditionally focused on psychological and neuronal mechanisms of...
Article
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Recent findings linked gastrointestinal disorders characterized by abdominal pain to gut microbiota composition. The present work aimed to evaluate the power of gut microbiota as a visceral pain modulator and, consequently, the relevance of its manipulation as a therapeutic option in reversing post-inflammatory visceral pain persistence. Colitis wa...
Article
Various lifestyle and environmental factors are known to influence sleep. Increasingly, evidence points to a role for the microbiota in regulating brain and behaviour. This article explores how the microbiota-gut-brain axis affects sleep directly and indirectly. We summarize the possible molecular mechanisms underlying sleep-microbiome interactions...
Article
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Interactions between the intestinal microbiota, immune system and nervous system are essential for homeostasis in the gut. Inflammasomes contribute to innate immunity and brain-gut interactions, but their role in microbiota-neuro-immune interactions is not clear. Therefore, we investigated the effect of the inflammasome on visceral pain and local a...
Article
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Recent investigations in neuroscience implicate the role of microbial-derived metabolites, such as short-chain fatty acids (SCFAs) in brain health and disease. The SCFAs acetate, propionate and butyrate have pleiotropic effects within the nervous system. They are crucial for the maturation of the brain’s innate immune cells, the microglia, and modu...
Article
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The gut microbiota is increasingly recognized as an important regulator of host immunity and brain health. The aging process yields dramatic alterations in the microbiota, which is linked to poorer health and frailty in elderly populations. However, there is limited evidence for a mechanistic role of the gut microbiota in brain health and neuroimmu...
Article
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Long-term high-fat diet (HFD) consumption commonly leads to obesity, a major health concern of western societies and a risk factor for Alzheimer's disease (AD). Both conditions present glial activation and inflammation and show sex differences in their incidence, clinical manifestation, and disease course. HFD intake has an important impact on gut...
Article
The last decade has witnessed a dramatic rise in the field of microbiota-gut-brain axis research, with strong evidence linking the composition of the gut microbiota with the structure and function of the brain. Emerging evidence highlights the crucial role of gut microbiota in orchestrating central nervous system (CNS) myelination. However, the mec...
Article
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In recent years, studies investigating the role of the gut microbiota in health and diseases have increased enormously-making it essential to deepen and question the research methodology employed. Fecal microbiota transplantation (FMT) in rodent studies (either from human or animal donors) allows us to better understand the causal role of the intes...
Article
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Visceral hypersensitivity (VH) is a hallmark of many functional gastrointestinal disorders including irritable bowel syndrome and is categorised by a dull, diffuse sensation of abdominal pain. Recently, the gut microbiota has been implicated in visceral hypersensitivity in male mice, but the effects in females has yet to be explored fully. To this...
Article
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Hippocampal neurogenesis has been shown to play roles in learning, memory, and stress responses. These diverse roles may be related to a functional segregation of the hippocampus along its longitudinal axis. Indeed, the dorsal hippocampus (dHi) plays a predominant role in spatial learning and memory, while the ventral hippocampus (vHi) is predomina...
Article
Full-text available
Autism spectrum disorder (ASD) is one of the most severe developmental disorders, affecting on average 1 in 150 children worldwide. There is a great need for more effective strategies to improve quality of life in ASD subjects. The gut microbiome has emerged as a potential therapeutic target in ASD. A novel modulator of the gut microbiome, the trad...
Article
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Functional GABAB receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on GABAB receptors [11, 71]) are formed from the heterodimerization of two similar 7TM subunits termed GABAB1 and GABAB2 [11, 70, 28, 71, 87]. GABAB receptors are widespread in the CNS and regulate both pre- and postsynaptic activity. The GABAB1 subunit, when expressed...
Preprint
Full-text available
Background/Objectives: Faecal microbiota transplant (FMT) is a powerful tool used to connect changes in gut microbial composition with a variety of disease states and pathologies. While FMT enables potential causal relationships to be identified, the experimental details reported in preclinical FMT protocols are highly inconsistent and/or incomplet...
Article
Full-text available
Whey protein isolate (WPI) is considered a dietary solution to obesity. However, the exact mechanism of WPI action is still poorly understood but is probably connected to its beneficial effect on energy balance, adiposity, and metabolism. More recently its ability to modulate the gut microbiota has received increasing attention. Here, we used a mic...
Article
Full-text available
Stress is a fundamental biological response that can be associated with alterations in cognitive processes. Unhealthy dietary habits are proposed to modulate this effect, notably through their pro-inflammatory potential. This cross-sectional study aimed to evaluate the influence of an obesogenic dietary pattern with inflammatory potential on stress...
Article
Full-text available
Irritable bowel syndrome (IBS) is a gut‐brain disorder in which symptoms are shaped by serotonin acting centrally and peripherally. The serotonin transporter gene SLC6A4 has been implicated in IBS pathophysiology, but the underlying genetic mechanisms remain unclear. We sequenced the alternative P2 promoter driving intestinal SLC6A4 expression and...
Article
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The oxytocin (OXT) system has been strongly implicated in the regulation of social behaviour and anxiety, potentially contributing to the aetiology of a wide range of neuropathologies. Birth by Caesarean-section (C-section) results in alterations in microbiota diversity in early-life, alterations in brain development and has recently been associate...
Chapter
Since the beginning of life on earth, microorganisms have played a significant role in evolution. Throughout the history of Homo sapiens and its precursor humanoid forms, microorganisms have been present at birth and proliferated until death. It is at these extremes of life that the microbiome, especially that within the gastrointestinal tract, is...
Chapter
The gut-brain axis is a bidirectional communication system which allows the central nervous system and gastrointestinal tract to interact with and respond to each other rapidly and effectively. It is becoming increasingly clear that major players in this complex system are gut bacteria. The mechanisms of signal transmission from bacteria to the bra...