The Relationship Between the Gut Microbiome-Immune System-Brain Axis and Major Depressive Disorder
Despite some controversies and some as yet unanswered questions about integration and about composition of the gut microbiome, the axis involving the gut, the immune system and brain function has exciting implications for furthering our understanding of the etiology of MDD and for its treatment.
Microbiota-immune alterations in adolescents following early life adversity: A proof of concept study
This proof-of-concept paper examined the microbiota composition in US adolescents born in the US or internationally adopted in the first few years of life. It mapped long-term changes in the microbiome and their association with immune phenotype.
Modulating brain function with microbiota
Microbial metabolites identified in animal models and human neurological diseases could be therapeutic targets.
Targeting the microbiome for mental health: Hype or hope?
This TINS review (highly cited paper – 536 as of May 12, 2019) and the Biological Psychiatry commentary were invited publications in high impact journals and reflect the international reputation of the Foster Lab research program. The cover of the May TINS issue that included this report was an artwork generated in collaboration between science, art, philosophy and technology.
Decoding Microbiome Research for Clinical Psychiatry
Overall, evidence in healthy and clinical populations show that microbes influence brain function and behavior. Much of the work to date has examined gut microbiome composition, and more studies are needed that utilize functional readouts such as metagenomics and metabolomics. Active studies continue to add to our knowledge of how genes and environment influence microbiota–brain interactions in mental health.
Metabolomic signature associated with depression and predictors of antidepressant response in humans: A CAN-BIND-1 report
This paper identified sex-specific predictors of anti-depressant response in a large clinical trial using metabolomic phenotyping in combination with clinical characteristics and anti-depressant response. The integration of these predictive signatures with other markers identified via different modalities by the CAN-BIND network will facilitate the construction of a multi-level, personalized signature of MDD and of antidepressant response useful for clinical practice. Efforts to optimize the treatment pipeline are essential to counter the pressing, growing burden of MDD toward accurate personalized treatments.
MicroRNAs 146a/b-5p, 424-3p, and 24-3p are consistent markers of antidepressant response and regulate MAPK/Wnt system genes.
This paper is representative of the molecular work that is being conducted in the CAN-BIND network in partnership with clinical researchers, molecular researchers, and industry. Dr. Gustavo Turecki from the Douglas Hospital Research Institute and Dr. Foster co-lead the Molecular Program for the CAN-BIND program.
Gut-brain axis: How the microbiome influences anxiety and depression.
Significant progress has been made over the past decade in recognizing the importance of gut microbiota to brain function. Key findings show that stress influences the composition of the gut microbiota and that bidirectional communication between microbiota and the CNS influences stress reactivity. Several studies have shown that microbiota influence behavior and that immune challenges that influence anxiety- and depressive-like behaviors are associated with alterations in microbiota.
A pilot dose finding study of piloglitazone in children with ASD
This paper stems from ongoing collaborative clinical work examining immune alterations in children with autism between the Foster Lab and Dr. Evdokia Anagnostou at Bloorview Research Institute in Toronto. Related to this work, I am the lead of the Immune Platform for the POND network. The development of the POND Immune Platform was a direct result of the basic science research program in the Foster Lab examining immune-brain communication in brain development and behavior. Pioglitazone is well-tolerated and shows a potential signal in measures of social withdrawal, repetitive, and externalizing behaviors. Randomized controlled trials using the confirmed dose are warranted.
Microbe-Immune Crosstalk: Evidence That T Cells Influence the Development of the Brain Metabolome
The present study demonstrated that T-cell deficiency alters the development of the gut microbiota and of the host’s gastrointestinal and brain metabolome. While the influence of the microbiome on immune development is well-established [4], the results of the current study demonstrate clearly the bidirectional nature of this relationship and identify several key taxa that are important to microbiota-immune crosstalk during postnatal development. Notably, the gut-related changes in microbial composition, diversity, and metabolite profile were accompanied by parallel changes in the hippocampal and hypothalamic metabolome.
Loss of T cells influences sex differences in behavior and brain structure
This is a key paper in a series of related papers from Foster Lab 1.0 that links T lymphocytes to brain function and behavior. Importantly, we have established that sex differences in these domains are influenced by the peripheral immune system in mice and ongoing work examines this association in clinical populations.
Reduced anxiety-like behavior and central neurochemical change in germ free mice.
We conclude that the presence or absence of conventional intestinal microbiota influences the development of behavior and is accompanied by neurochemical changes in the brain.
Microbe-Immune-Stress Interactions Impact Behavior during Postnatal Development
Integrated analyses of microbiota and behavior in the context of immunocompromise revealed key behavioral related taxa that may be important to brain development. These findings are important to determining the influence of genetic and environmental factors on gut microbiota and advances our understanding microbiome-brain signaling pathways on neurodevelopment and behavior.
Is Anxiety Associated with the Gut Microbiota?
Consideration of anxiety-like behavior in animal models of metabolic and inflammatory disorders expands the scope of the work and correlates in clinical studies are emerging. This chapter highlights the work done to date in animal studies and reviews the recent clinical literature translating these observations to anxiety disorders.
Microbes and mental health: Can the microbiome help explain clinical heterogeneity in psychiatry?
This review provides an overview of the factors contributing to individual differences in the microbiome, reviews recent work in psychiatric disorders, and considers what is needed to advance a better understanding of how the microbiome impacts mental health which may help us understand the heterogeneity observed in clinical psychiatric populations.
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