Microbiota, the immune system, black moods and the brain—melancholia updated

There is now abundant evidence that the immune system and the brain have close functional interactions in both directions. This review focuses on the influence of the microbiota (the bacteria resident in the gut) on brain function in major depressive disorder (MDD) and related syndromes. The gut and the central nervous system communicate partly through the autonomic nervous system (ANS), consisting of the sympathetic (i.e., the splanchnic nerves) and the parasympathetic (i.e., the vagus nerve and the sacral parasympathetic pelvic nerves) nervous system. The brain integrates inputs from the digestive tract by a central autonomic network that includes the hypothalamus, limbic system and cerebral cortex with output to the ANS and hypothalamic-pituitary-adrenal gland (HPA) stress axis (Bonaz, 2013). There are also extensive chemical signaling systems via the blood.

• Publication year

  2014

• Venue

  Frontiers in Human Neuroscience

• Publication date

  2014-09-15

• Fields of study

  Medicine, Psychology

• Identifiers
  DOI 10.3389/fnhum.2014.00720PMID 25309394PMCID 4163975
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Expression of Toll-Like Receptors in peripheral blood mononuclear cells and response to cognitive-behavioral therapy in major depressive disorder.

  2014cited by this paper
• Immunology of Major Depression

  2014influential reference
• From stress to inflammation and major depressive disorder: a social signal transduction theory of depression.

  2014cited by this paper
• Probiotic gut effect prevents the chronic psychological stress‐induced brain activity abnormality in mice

  2014cited by this paper
• Nervous and immune systems signals and connections: cytokines in hippocampus physiology and pathology.

  2014cited by this paper
• Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity.

  2014cited by this paper
• The role of DNA methylation in stress-related psychiatric disorders.

  2014cited by this paper
• Extracellular Vesicle-Mediated Transfer of Genetic Information between the Hematopoietic System and the Brain in Response to Inflammation

  2014cited by this paper
• Is there an association between peripheral immune markers and structural/functional neuroimaging findings?

  2014cited by this paper
• Exosomes in the gut

  2014cited by this paper
• Stress-induced neuroinflammation: role of the Toll-like receptor-4 pathway.

  2013cited by this paper
• Melancholic microbes: a link between gut microbiota and depression?

  2013cited by this paper
• Bacteria activate sensory neurons that modulate pain and inflammation

  2013influential reference
• So depression is an inflammatory disease, but where does the inflammation come from?

  2013cited by this paper
• Depression, antidepressant medications, and risk of Clostridium difficile infection

  2013cited by this paper
• Role of the Toll Like Receptor (TLR) Radical Cycle in Chronic Inflammation: Possible Treatments Targeting the TLR4 Pathway

  2013cited by this paper
• Immune–neural connections: how the immune system’s response to infectious agents influences behavior

  2013cited by this paper
• Microbiota-mediated colonization resistance against intestinal pathogens

  2013cited by this paper
• Inflammatory bowel diseases: a dysfunction of brain-gut interactions?

  2013influential reference
• The role of psychosocial factors and psychiatric disorders in functional dyspepsia

  2013cited by this paper
• Body Fluid Exosomes Promote Secretion of Inflammatory Cytokines in Monocytic Cells via Toll-like Receptor Signaling*

  2013cited by this paper
• Stress and visceral pain: Focusing on irritable bowel syndrome

  2013cited by this paper
• Altered colonic function and microbiota profile in a mouse model of chronic depression

  2013cited by this paper
• In depression, bacterial translocation may drive inflammatory responses, oxidative and nitrosative stress (O&NS), and autoimmune responses directed against O&NS‐damaged neoepitopes

  2013cited by this paper
• TLR7 Negatively Regulates Dendrite Outgrowth through the Myd88–c-Fos–IL-6 Pathway

  2013cited by this paper
• Altered neuro-endocrine–immune pathways in the irritable bowel syndrome: the top-down and the bottom-up model

  2012cited by this paper
• Goblet cells deliver luminal antigen to CD103+ DCs in the small intestine

  2012cited by this paper
• Increased IgA and IgM responses against gut commensals in chronic depression: further evidence for increased bacterial translocation or leaky gut.

  2012cited by this paper
• Outer membrane vesicles of a human commensal mediate immune regulation and disease protection.

  2012cited by this paper
• Exposure to a social stressor alters the structure of the intestinal microbiota: implications for stressor-induced immunomodulation.

  2011cited by this paper
• Origin and consequences of brain Toll-like receptor 4 pathway stimulation in an experimental model of depression

  2011cited by this paper
• Depression is an inflammatory disease, but cell-mediated immune activation is the key component of depression.

  2011cited by this paper
• Inflammatory mechanisms in major depressive disorder

  2011cited by this paper
• Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve

  2011cited by this paper
• A meta-analysis of cytokines in major depression.

  2010cited by this paper
• Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression.

  2009cited by this paper
• A Meta-Analysis

  2009cited by this paper
• Available online at:

  2009cited by this paper
• Chronic Interpersonal Stress Predicts Activation of Pro- and Anti-Inflammatory Signaling Pathways 6 Months Later

  2009cited by this paper
• Nerve growth factor, interoception, and sympathetic neuron: lesson from congenital insensitivity to pain with anhidrosis.

  2009cited by this paper
• The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression.

  2008cited by this paper
• Toll-like receptors — taking an evolutionary approach

  2008cited by this paper
• TLR-4, IL-1R and TNF-R signaling to NF-κB: variations on a common theme

  2008cited by this paper
• STAT3 activation and c-FOS expression in the brain following peripheral administration of bacterial DNA.

  2005cited by this paper
• Inflammatory mechanisms.

  2001cited by this paper
• The role of inflammatory mediators in the biology of major depression: central nervous system cytokines modulate the biological substrate of depressive symptoms, regulate stress-responsive systems, and contribute to neurotoxicity and neuroprotection

  1999cited by this paper
• Involvement of reactive oxygen intermediates in cyclooxygenase-2 expression induced by interleukin-1, tumor necrosis factor-alpha, and lipopolysaccharide.

  1995cited by this paper
• Depression and immunity: a meta-analytic review.

  1993cited by this paper

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• Chronic skin damage induces small intestinal damage via IL-13-induced apoptosis.

  2024cites this paper
• The Gut Microbiota and Major Depressive Disorder: Current Understanding and Novel Therapeutic Strategies.

  2024cites this paper
• Microbiome-Induced Autoimmunity and Novel Therapeutic Intervention.

  2023cites this paper
• Beneficial Bacteria Isolated from Food in Relation to the Next Generation of Probiotics

  2023cites this paper
• Psychobiotics: Are they the future intervention for managing depression and anxiety? A literature review

  2023cites this paper
• Monoamine Neurotransmitters Control Basic Emotions and Affect Major Depressive Disorders

  2022cites this paper
• Knowledge, patterns of consumption, and attitudes of patients with major depression disorders toward probiotics

  2021cites this paper
• Effectiveness of vestibular stimulation on selected biochemical parameters in young adults

  2020cites this paper
• Potential role of phytochemicals in brain plasticity: Focus on polyunsaturated fatty acids

  2020cites this paper
• The future of quantum dot fluorescent labelling of extracellular vesicles for biomedical applications

  2020cites this paper
• Physiological phenotypes and urinary metabolites associated with the psychological changes of healthy human: A study in ‘‘lunar palace 365”

  2020cites this paper
• Perioperative neurocognitive dysfunction: thinking from the gut?

  2020influential citation
• Emerging role of Gut-microbiota-brain axis in depression and therapeutic implication.

  2020cites this paper
• Art and the Microbiome

  2020cites this paper
• Gut Microbiome in Health and Disease

  2019cites this paper
• Fecal Microbiota Transplantation in the Treatment-Resistant Psychiatric Disorders

  2018cites this paper
• Gut-Microbiota-Brain Axis and Depression

  2018cites this paper
• Brain Plasticity and Experience

  2018cites this paper
• Gut-Brain Psychology: Rethinking Psychology From the Microbiota–Gut–Brain Axis

  2018cites this paper
• [The intestinal microbiota: A new player in depression?]

  2017cites this paper
• Microbiome: The Missing Link in Neuropsychiatric Disorders

  2017cites this paper
• Stress & the gut-brain axis: Regulation by the microbiome

  2017cites this paper
• Early interventions in risk groups for schizophrenia: what are we waiting for?

  2016cites this paper
• GutMicrobiota-derivedOuterMembrane Vesicles:UnderRecognizedMajorPlayers inHealthandDisease? MAu r Iz Io Mu r AcA , L or eNz A Pu t IgNANI , A LeSSANdr A FIer Abr AccI , ANNA t et I , ANd gIor gIo Per ILoNgo

  2015cites this paper
• News Feature: Microbes on the mind

  2015cites this paper
• Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders

  2015cites this paper
• Zinc in Gut-Brain Interaction in Autism and Neurological Disorders

  2015cites this paper
• Tuning the Brain-Gut Axis in Health and Disease

  2015cites this paper
• The Gut-Brain Axis: The Missing Link in Depression

  2015cites this paper
• Bağirsak Beyin Ekseni: Psikiyatrik Bozukluklarda Bağirsak Mikrobiyotasinin Rolü-Brain Axis: The Role of Gut Microbiota in Psychiatric Disorders

  2015cites this paper