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Psychopharmacology of the Visceral Immune – Brain Axis

Being one of the most prevalent and severe mood disorders, major depression is deleterious to the patients’ quality of life and of enormous socio-economic impact. According to the World Health Organization, depression is the second most frequent cause of disability-adjusted life years in the age category of 15 – 44 years for both genders, with the number of patients continuing to grow. A proportion of some 40 % of the patients does not satisfactorily respond to the available antidepressant drugs, which reflects the incomplete understanding of the aetiology of affective disorders. Apart from vulnerability and psychosocial factors, chronic immune challenge has emerged as a circumstance relevant to the pathogenesis of mood disorders. The cytokine hypothesis of depression holds that systemic inflammatory processes associated with elevated levels of circulating proinflammatory cytokines disturb several brain mechanisms that control anxiety, mood, stress resilience and cognition.
Visceral immune activation and inflammation are associated with a variety of psychiatric abnormalities, and there is clinical evidence that constituents of the intestinal microbiota across a leaky mucosal barrier may be a factor underlying mood disorders. Preclinical evidence indicates that gastrointestinal infection and inflammation as well as intraperitoneal administration of bacterial lipopolysaccharide induce behavioural disturbances. The current research proposal sets out to specifically examine the visceral immune – brain axis in an innovative and comprehensive manner and to identify key mechanisms that are suitable for pharmacological modulation.
The main hypotheses to be addressed are that
• factors derived from the intestinal microbiota (lipopolysaccharide, pepidoglycan) or intestinal hormones under the regulatory influence of the microbiota (glucagon-like peptide, peptide YY) have an impact on the visceral immune – brain axis;
• visceral immune challenge has a short- and long-term impact on affective behaviour;
• specific brain signalling mechanisms involving receptor-activator of nuclear factor B ligand, cyclooxygenase-2 and brain-derived neurotrophic factor play a role in the behavioural effects of peripheral immune challenge; and
• activation of the visceral immune – brain axis is associated with deranged activity of the hypothalamic-pituitary-adrenal axis, disturbed glucocorticoid feedback on the brain and altered neurogenesis in the limbic system.
Mikrobielle Metaboliten
Project Leader:
Holzer Peter
Type of Research
basic research
Holzer P., Project Leader
Reichmann F., Co-worker
Farzi A., Co-worker
Jacan A., Co-worker
HASSAN A., Co-worker
Mayerhofer R., Co-worker
Fröhlich E., Co-worker
MUG Research Units
Division of Pharmacology
Funded by
FWF, Fonds zur Förderung der Wissenschaftlichen Forschung, Wien, Austria

FWF-Project-Link: P25912
Project results published
> Experimental colitis reduces microglial cell activ... Sci Rep. 2019; 9(1): 20217-20217.
> Diabesity and mood disorders: Multiple links throu... Mol Aspects Med. 2019; 66(2):80-93
> High-fat diet induces depression-like behaviour in... Nutr Neurosci. 2019; 22(12):877-893
> Neuropeptide Y in gut-brain communication.... NPY-PYY-PP 12th International Meeting; JUL 27-31, 2019; Edmonton, CANADA. 2019.
> Gut Microbiota and the Neuroendocrine System.... Neurotherapeutics. 2018; 15(1): 5-22.
> Diverse action of lipoteichoic acid and lipopolysa... Brain Behav Immun. 2017; 60(3):174-187
> Visceral Inflammation and Immune Activation Stress... Front Immunol. 2017; 8:1613-1613
> Visceral hyperalgesia caused by peptide YY deletio... Sci Rep. 2017; 7(6):40968-40968
> Neuropeptide Y: A stressful review.... Neuropeptides. 2016; 55:99-109
> Effects on the circulating metabolome in an antibi... The 1st International Conference on Microbiota-Gut-Brain Axis: Mind, Mood & Microbes; DEC 1-2, 2016; Amsterdam, THE NETHERLANDS. 2016.
> Gut-brain axis in antibiotic-induced gut dysbiosis... Abstracts of the GENIEUR Final Conference. 2016; 21-21.-COST Action BM 1106 GENIEUR Final Conference; MAR 14-15, 2016; Heidelberg, GERMANY.
> Darmhormone/Neuropeptide und die Darmmikrobiom-Geh... DACH-Tagung der DGE, ÖGES und SGED; MAY 26-28, 2016; Munich, GERMANY. 2016.
> Die Darmmikrobiom-Gehirn-Achse: Neurogastroenterol... Abstrakts, Psychosomatischer Freitag. 2016; -Psychosomatischer Freitag; JUL 1, 2016; Hohenems, AUSTRIA.
> Antibiotic- and nutrition-induced disturbances of ... 3rd Theodor Escherich Symposium on Medical Microbiome Research; NOV 4, 2016; Graz, AUSTRIA. 2016.
> Die Mikrobiom-Darm-Gehirn-Achse.... Abstracts, Programm und Informationen. 2016; 34-39.-Pharmacon. 46. Internationale Pharmazeutische Fortbildungswoche der Bundesapothekerkammer; JAN 17-22, 2016; Schladming, AUSTRIA.
> Cognitive impairment by antibiotic-induced gut dys... Brain Behav Immun. 2016; 56(6):140-155
> Antibiotic-induced gut dysbiosis affects cerebral ... 22nd Scientific Symposium of APHAR; SEP 8-10, 2016; Vienna, AUSTRIA. 2016.
> Neuropeptides, Microbiota, and Behavior.... Int Rev Neurobiol. 2016; 131(12):67-89
> Neurogastroenterologie: Darm und Gehirn im Fokus.... Neurologisch. 2016; Ausgabe 2/16(2): 28-30.
> Lifestyle and the Gut: Pathophysiology and Treatme... In: Sommer, C; editors(s). Pain 2016: Refresher Courses, 16th World Congress on Pain. Washington, D.C.: IASP Press; p. 439 - 446. 2016
> Antibiotic- and diet-induced effects on the gut mi... Abstracts of Physiology 2016. 2016; 47P-48P.-Physiology 2016 (Joint Meeting of the American Physiological Society and The Physiological Society); JUL 29-31, 2016; Dublin, IRELAND.
> Mikrobiom und Gehirn.... Qualitätszirkel der Fachgruppe Psychiatrie der Ärztekammer OÖ; MAY 24, 2016; Linz, AUSTRIA. 2016.
> Das Gehirn unter dem Einfluss des Darmmikrobioms.... Neurologisch. 2015; 1/15(1/15): 45-49.
> Neuropeptide und die Mikrobiota-Darm-Gehirn-Achse.... 19. Jahrestagung der Sektion Neuroendokrinologie der Deutschen Gesellschaft für Endokrinologie; Nov 20, 2015; Munich, GERMANY. 2015.
> Die Mikrobiom-Darm-Hirn-Achse... Nutrition News. 2015; 12(3/15): 1-4.
> Neuropeptide Y knockout alters behavioural effects... Intrinsic Activity. 2015; 3(Suppl. 2): -21st Scientific Symposium of the Austrian Pharmacological Society: Joint Meeting with the British Pharmacological Society and the Pharmacological Societies of Croatia, Serbia and Slovenia; SEP 16-18, 2015; Graz, AUSTRIA.
> Neuroimmune pharmacological approaches.... Curr Opin Pharmacol. 2015; 25:13-22
> Dextran sulfate sodium-induced colitis alters stre... Sci Rep. 2015; 5(6):9970-9970
> Toll-like receptor 4 contributes to the inhibitory... Sci Rep. 2015; 5(5):9499-9499
> Reevaluating the hype: four bacterial metabolites ... Eur J Microbiol Immunol (Bp). 2015; 5(1):1-13
> The homeostatic role of neuropeptide Y in immune f... Acta Physiol (Oxf). 2015; 213(3):603-627
> ANXIOLYTIC EFFECTS OF ENVIRONMENTAL ENRICHMENT ARE... Abstract Book of the 1st joint meeting of the European Brain and Behaviour Society and the European Behavioural Pharmacological Society. 2015; -1st joint meeting of the European Brain and Behaviour Society and the European Behavioural Pharmacological Society ; SEP 12-15, 2015; Verona, ITALY.
> A novel unbiased counting method for the quantific... J Neurosci Methods. 2015; 240(6):13-21
> Synergistic effects of NOD1 or NOD2 and TLR4 activ... Brain Behav Immun. 2015; 44(1):106-120
> Behavioral and molecular processing of visceral pa... Front Behav Neurosci. 2015; 9(5):177-177
> Neuropeptides and the microbiota-gut-brain axis.... Adv Exp Med Biol. 2014; 817(4):195-219
> Repeated predictable stress causes resilience agai... Front Behav Neurosci. 2014; 8(6):386-386
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