Associations between short-chain fatty acid levels and mood disorder symptoms: a systematic review

ABSTRACTBackground: Available evidence points to a possible role of Short Chain Fatty Acids (SCFAs) in mood disorders. This is the first systematic review to map the associations between SCFA levels and mood disorder symptoms.Methods: Following the PRISMA guidelines, the databases PubMed, Embase, and PsycINFO were searched for studies that assessed SCFA levels in human populations with mood disorder symptoms, or animal models of mood disorder. Risk of bias was assessed by the Strengthening of Reporting of Observational Studies in Epidemiology (STROBE) checklist.Results: 19 studies were included and could be divided into animal (n=8) and human studies (n=11), with the animal studies including 166 animals and 100 controls, and the human studies including 662 participants and 330 controls. The studies were characterized by heterogeneity and methodological challenges on multiple parameters, limiting the validity and transferability of findings. Notably, only two of the clinical studies assessed the presence of mood disorder with diagnostic criteria, and no studies of mania or bipolar disorder met the inclusion criteria.Discussion: Despite significant methodological limitations, associations between SCFA levels and depressive symptoms were reported in most of the studies. However, the direction of these associations and the specific SCFAs identified varied. The quantification of SCFA levels in mood disorders is an emerging yet sparsely studied research field. Although there is some evidence suggesting a link between SCFAs and depressive symptoms, the directionality of effects and mechanisms are unclear and the relation to manic symptoms is uninvestigated.KEYWORDS: AcetateAffective disorders‌ButyrateDepressionGut-brain-axisMood disorderPropionate‌Short chain fatty acids Disclosure statementNo potential conflict of interest was reported by the author(s).Data availability statementData and materials are available upon request.Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.Notes on contributorsCaroline Fussing BruunCaroline Fussing Bruun, MD, is a PhD student at the Copenhagen Affective DIsorder research Centre (CADIC) at the Psychiatric Center Copenhagen and the University of Copenhagen.Tue Haldor HansenTue Haldor Hansen, MD, PhD, is a postdoc researcher at the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen. He is the author of 85 scientific papers.Maj VinbergMaj Vinberg is a professor in psychiatry at Mental Health Centre, Northern Zealand, and Copenhagen University. Dr. Vinberg´s area covers new integrated treatments, including biomarkers involving interdisciplinary clinical trials targeting patients with affective disorders to maintain and regain their functional ability, and she is the author of more than 250 scientific papers.Lars Vedel KessingLars Vedel Kessing has since 2002 been appointed as professor in psychiatry at the Psychiatric Center Copenhagen and at the University of Copenhagen. Dr. Kessing's scientific focus is within clinical, epidemiological and neurobiological research in affective disorders and he is the author of more than 550 scientific papers.Klara CoelloKlara Coello, MD, PhD, resident in psychiatry and postdoc researcher within the field of bipolar disorder and biological biomarkers. More specifically, her scientific focus is on accelerated aging, the gut-brain axis, and the prevention of illness onset and progression.