Microbiota Regulation of Brain Function and Disease

May 16-23, 2026

Director: John Cryan

University College, Cork, Ireland

Faculty:

Jane Foster, UT Southwestern, Dallas, USA

Rochellys Diaz Heijtz, Karolinska Institute, Stockholm, Sweden

Arpana Church, University of California, Los Angeles, USA

Jonathan Swann, University of Southampton, UK

Premysl Bercik, McMaster University, Hamilton, Canada

Mireia Valles-Colomer, Pompeu Fabra University, Barcelona, Spain

Aletta Kraneveld, Vrije Universiteit Amsterdam, Netherlands

John Cryan, University College, Cork, Ireland

The gut microbiome is now recognised as a key regulator of health and disease across virtually all body systems—including the brain. The microbiota–gut–brain axis has emerged as a major focus of research in neurodevelopmental, neurodegenerative, age-related, and psychiatric disorders. While much of the evidence derives from model systems, the precise pathways of gut–brain communication are still being clarified. Proposed routes include the vagus nerve, the immune system, tryptophan metabolism, the enteric nervous system, and microbial metabolites such as short-chain fatty acids (SCFAs).

Animal studies have shown that a healthy stress response depends on the microbiota. Early-life factors, including birth mode, antibiotic use, nutrition, infection, stress, and host genetics, shape microbiome development. In contrast, reduced microbial diversity in later life is often linked to poor health. Stress impacts the microbiota–gut–brain axis across the lifespan, contributing to disorders such as depression, anxiety, and irritable bowel syndrome. Beyond these, the microbiome has been implicated in conditions including autism spectrum disorder, traumatic brain injury, stroke, multiple sclerosis, Alzheimer’s disease, and Parkinson’s disease. At a mechanistic level, fundamental brain processes—from hippocampal neurogenesis and blood–brain barrier integrity to myelination and microglial activation—are now understood to be influenced by the microbiome.

This Advanced Course will explore the tools and strategies used to investigate how the microbiome influences brain function and behaviour. The Faculty will cover the full spectrum of microbiome science—from basic mechanisms to clinical medicine and population-level studies—highlighting its intersections with neuroimmunology, neuroendocrinology, nutrition, neurology, and psychiatry. The programme will also critically examine both the promise and the hype surrounding nutritional and microbial-based interventions for brain disorders. It is designed for basic and clinical scientists at all career stages. All sessions will emphasise open, interactive discussion, with strong encouragement for participants to actively engage with the Faculty.

Rochellys Diaz Heijtz

Mechanisms of the microbiota–gut–brain axis in neurodevelopmental disorders

The gut microbiota is a crucial regulator of brain development and behavior, and growing evidence suggests that changes in the maternal microbiome during pregnancy, as well as disruptions to early-life microbial colonization, may increase vulnerability to neurodevelopmental and psychiatric disorders. The lectures will offer an integrated overview of the main biological pathways through which the gut microbiota communicates with the developing brain, focusing on microbial metabolites, immune-mediated signalling, and the development and maturation of neural circuits. A major focus will be on how microbially derived metabolites, cytokines, and peptidoglycan fragments influence neurodevelopmental processes and shape brain circuit formation. Recent translational insights from human cohort studies and animal models will also be a significant topic, highlighting potential causal links between early-life dysbiosis and altered neurodevelopmental trajectories. Finally, we will delve into emerging microbiome-based interventions, including probiotics, postbiotics, and strategies to modulate the microbiome during the prenatal and postnatal periods, integrating evidence from both human and animal research that highlights their promise for early prevention and treatment of NDDs. Key challenges and future directions for advancing these approaches towards clinical application will be highlighted throughout the lectures.

John Cryan

Unravelling mechanisms of microbiota-gut-brain-axis signalling across the lifespan

These lectures highlight how recent evidence suggests that the communication between the microbiome and the brain along the gut–brain axis has gained prominence as a potential tractable target to modulate brain health. Over the past two decades, it has been shown that the microbiota and the brain communicate with each other via various routes, including the immune system, the vagus nerve and the enteric nervous system and microbial metabolites such as short-chain fatty acids, branched-chain amino acids, and peptidoglycans. Many factors can influence microbiota composition in early life, including infection, mode of birth delivery, use of antibiotic medications, the nature of nutritional provision, environmental stressors, and host genetics. At the other extreme of life, microbial diversity diminishes with aging. Stress, in particular, can significantly impact the microbiota-gut-brain axis at all stages of life. Animal models have been paramount in linking the regulation of fundamental neural processes, such as neurogenesis and myelination, to microbiome activation of microglia. Moreover, translational human studies are ongoing and will significantly enhance the field. Future studies will focus on understanding the causal mechanisms underlying the microbiota-gut-brain axis and attempt to elucidate microbial-based intervention and therapeutic strategies for neuropsychiatric disorders. Moreover, dietary factors are being harnessed to alter gut–brain signalling and a diet–microbiota–gut–brain has been proposed, which underpins health and well-being.

Mireia Valles-Colomer

Elucidating the role of the microbiota and its neuroactive potential in neuropsychiatry

These lectures will introduce cutting-edge computational methods for analysing microbiome data to better understand the role of gut microorganisms in brain function and mental health. Participants will gain insights into bioinformatic and statistical strategies for integrating metagenomic, metabolomic, and clinical data, enabling the identification of microbial taxa and metabolic pathways linked to neuropsychiatric outcomes. The sessions will also explore the social aspect of the microbiome, presenting recent evidence that behaviour shapes the interpersonal transmission of microbial communities, which may subsequently affect host physiology and mental health. Building on findings from large-scale population studies, the lectures will highlight how microbial neuroactive compounds could impact mental health, providing mechanistic insights into the microbiota-gut-brain axis. Finally, future directions will be discussed, including the integration of longitudinal and multi-omics datasets, causal inference frameworks, and experimental validation to unravel how microbiota variation affects brain function. These advances will be crucial for translating microbiome research into predictive models and microbiota-targeted interventions aimed at improving mental health and well-being.

Arpana Church

Stress, human brain imaging and the microbiome

This session will focus on how environmental stressors become embedded within the brain-gut microbiome system. The lectures will outline how these stressors are linked to a higher risk of developing adverse health outcomes such as obesity, abnormal eating behaviours, psychiatric and cognitive disorders. By emphasising adverse environmental factors, the session aims to highlight individuals who are at an increased risk of developing disease due to disadvantaged backgrounds. Additionally, examples will be provided of how resilience within the brain-gut microbiome system can be targeted to protect against or reduce the negative impacts of a stressful environment.

Jane Foster

Microbes and mental health: translating preclinical findings to clinical practice

For over 15 years, animal studies have shown that gut-brain signalling affects brain development, behaviour, and brain function, including key neural processes such as neurotransmission and neuroplasticity. Preclinical research demonstrates a mechanistic role for microbiota-host signalling in brain function and behaviour at multiple levels, including the microbiome, gut, metabolites, immune response, and brain. These studies provide a strong rationale to investigate specific gut-brain signalling pathways as biological mechanisms underlying clinical symptoms. Translating our understanding of microbiota-host mechanisms based on insight gleaned from preclinical studies to the clinic is the next frontier in clinical neuroscience research. In fact, several studies have emphasised the translational potential of the microbiome in animal models, which is further enhanced by functional mapping of candidate microbes to causal pathways in gut-brain communication and the parallel analysis of microbe-related biomarkers in human studies. Beyond case-control comparisons, it is essential to test mechanistic hypotheses within clinical populations. The lectures will offer a current overview of translational research related to the Microbiota Regulation of Brain Function and Disease.

Jonathan Swann

Deciphering the biomolecular language of the microbiota-gut-brain axis

The extensive influence of the intestinal microbiota on human health and disease is now well recognised. Co-evolution between the human host and its resident microbiota has produced a complex and dynamic holobiont whose fitness is determined by the combined contributions and interactions of these pan-kingdom entities. Over the past two decades, increasing evidence has convincingly demonstrated the existence of the microbiota-gut-brain axis, which has the potential to influence neurodevelopment, function (e.g., behaviour, cognition), and neurodegeneration. This bi-directional communication occurs through biochemical, immunological, and nervous pathways. Here, the main classes of metabolites involved in the biochemical aspects of this communication will be discussed, including short-chain fatty acids, bile acids, amino acid degradation products, and cell wall components. Additionally, the possibility of modulating these signals through dietary components will be explored, along with future perspectives for this field.

Aletta Kraneveld

Microbiome, neuroimmunology & neurodegeneration

Changes in the composition and activity of intestinal bacteria, the compromised intestinal barrier, and disturbed mucosal neuro-immune system, as well as low-grade systemic inflammation in patients, highlight the importance of the microbiota-gut-immune-brain axis in neurodegeneration. Based on (pre)clinical data, the lectures will examine the potential mechanisms of crosstalk between gut bacteria, the immune system, and the brain in Parkinson’s disease (PD), with a focus on neuroimmune mechanisms. Additionally, we will present our recent findings on the role of neuroimmune interactions in the enteric nervous system, a possible gateway to the brain.
There is a significant need for additional PD therapies that address both motor and non-motor symptoms. Recently, we demonstrated that pharmacological targeting of toll-like receptor 4 produces a beneficial effect in a pesticide-induced mouse model of PD. Additionally, we have shown that a diet containing nutritional precursors and cofactors, known to improve synaptic function, along with prebiotic fibres, had therapeutic effects in the same mouse model of PD and enhanced the efficacy of oral L-DOPA therapy. These and other reports highlight important interactions between diet, microbiota, and pharmaceuticals in PD.
Poor gut function leads to poor brain function, and vice versa. Therefore, targeting the microbiota-gut-immune-brain axis with nutritional interventions and/or pharmaceutical compounds could be a new approach for the (additional) therapy of PD, addressing both motor and non-motor dysfunctions.

Premysl Bercik

Bacterial metabolites in health and disease

The gut microbiome has been increasingly recognised as a key factor influencing gastrointestinal tract function, including intestinal permeability, motility, and visceral sensitivity. Gut microbiota produce diverse bioactive metabolites that signal through the immune system or directly interact with the neuromuscular apparatus. These microbiome-host interactions are not confined to the colon; they also occur in the small intestine, which has the highest density of immune cells in the digestive tract and where most food components are digested. Long-term diet is a major determinant of microbiota composition and function, providing gut bacteria with substrates for neuroactive and immunomodulatory metabolites. In this session, we will discuss the role of bacterial metabolites, such as histamine and bioactive phospholipids, in chronic abdominal pain, as well as comorbid anxiety and depression, in patients with Irritable Bowel Syndrome and Inflammatory Bowel Disease.