Depression-associated Gut Microbes, Metabolites and Clinical Trials

Overview

Journal Front Microbiol

Specialty Microbiology

Date 2024 Feb 15

PMID 38357350

Authors

Meiling Wang

Zhaoqi Song

Shirong Lai

Furong Tang

Lijun Dou

Fenglong Yang

Affiliations

Soon will be listed here.

Abstract

Depression is one of the most prevalent mental disorders today. Over the past decade, there has been considerable attention given to the field of gut microbiota associated with depression. A substantial body of research indicates a bidirectional communication pathway between gut microbiota and the brain. In this review, we extensively detail the correlation between gut microbiota, including and , and metabolites such as short-chain fatty acids (SCFAs) and 5-hydroxytryptamine (5-HT) concerning depression. Furthermore, we delve into the potential health benefits of microbiome-targeted therapies, encompassing probiotics, prebiotics, and synbiotics, in alleviating depression. Lastly, we underscore the importance of employing a constraint-based modeling framework in the era of systems medicine to contextualize metabolomic measurements and integrate multi-omics data. This approach can offer valuable insights into the complex metabolic host-microbiota interactions, enabling personalized recommendations for potential biomarkers, novel drugs, and treatments for depression.

Citing Articles

A study on the differences in the gut microbiota and metabolism between male and female mice in different stress periods.

Qiao Y, Guo J, Xiao Q, Wang J, Zhang X, Liang X Exp Biol Med (Maywood). 2025; 250:10204.

PMID: 40008145 PMC: 11851196. DOI: 10.3389/ebm.2025.10204.

GOS enhances BDNF-mediated mammary gland development in pubertal mice via the gut-brain axis.

Ge Y, Cao Y, Zhang J, Li F, Wang J, Sun M NPJ Biofilms Microbiomes. 2024; 10(1):130.

PMID: 39562762 PMC: 11577074. DOI: 10.1038/s41522-024-00607-4.

The interplay of gut microbiota, obesity, and depression: insights and interventions.

Halabitska I, Petakh P, Kamyshna I, Oksenych V, Kainov D, Kamyshnyi O Cell Mol Life Sci. 2024; 81(1):443.

PMID: 39476179 PMC: 11525354. DOI: 10.1007/s00018-024-05476-w.

Alterations in Vagal Tone Are Associated with Changes in the Gut Microbiota of Adults with Anxiety and Depression Symptoms: Analysis of Fecal Metabolite Profiles.

Pasqualette L, Fidalgo T, Freitas-Fernandes L, Souza G, Imbiriba L, Lobo L Metabolites. 2024; 14(8).

PMID: 39195546 PMC: 11356408. DOI: 10.3390/metabo14080450.

Role of Glial Cells in Neuronal Function, Mood Disorders, and Drug Addiction.

Tizabi Y, Getachew B, Hauser S, Tsytsarev V, Manhaes A, da Silva V Brain Sci. 2024; 14(6).

PMID: 38928557 PMC: 11201416. DOI: 10.3390/brainsci14060558.

References

Tahara Y, Yamazaki M, Sukigara H, Motohashi H, Sasaki H, Miyakawa H . Gut Microbiota-Derived Short Chain Fatty Acids Induce Circadian Clock Entrainment in Mouse Peripheral Tissue. Sci Rep. 2018; 8(1):1395. PMC: 5780501. DOI: 10.1038/s41598-018-19836-7. View

Heidarzadeh-Rad N, Gokmen-Ozel H, Kazemi A, Almasi N, Djafarian K . Effects of a Psychobiotic Supplement on Serum Brain-derived Neurotrophic Factor Levels in Depressive Patients: A Analysis of a Randomized Clinical Trial. J Neurogastroenterol Motil. 2020; 26(4):486-495. PMC: 7547201. DOI: 10.5056/jnm20079. View

Mahmoudiandehkordi S, Bhattacharyya S, Brydges C, Jia W, Fiehn O, Rush A . Gut Microbiome-Linked Metabolites in the Pathobiology of Major Depression With or Without Anxiety-A Role for Bile Acids. Front Neurosci. 2022; 16:937906. PMC: 9350527. DOI: 10.3389/fnins.2022.937906. View

Li Y, Cai H, Wang Z, Xu J, Fang J . Systematic review with meta-analysis: long-term outcomes of faecal microbiota transplantation for Clostridium difficile infection. Aliment Pharmacol Ther. 2015; 43(4):445-57. DOI: 10.1111/apt.13492. View

Tian T, Mao Q, Xie J, Wang Y, Shao W, Zhong Q . Multi-omics data reveals the disturbance of glycerophospholipid metabolism caused by disordered gut microbiota in depressed mice. J Adv Res. 2022; 39:135-145. PMC: 9263645. DOI: 10.1016/j.jare.2021.10.002. View

Kazemi A, Noorbala A, Azam K, Eskandari M, Djafarian K . Effect of probiotic and prebiotic vs placebo on psychological outcomes in patients with major depressive disorder: A randomized clinical trial. Clin Nutr. 2018; 38(2):522-528. DOI: 10.1016/j.clnu.2018.04.010. View

Paternain L, Martisova E, Campion J, Martinez J, Ramirez M, Milagro F . Methyl donor supplementation in rats reverses the deleterious effect of maternal separation on depression-like behaviour. Behav Brain Res. 2015; 299:51-8. DOI: 10.1016/j.bbr.2015.11.031. View

Agus A, Planchais J, Sokol H . Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease. Cell Host Microbe. 2018; 23(6):716-724. DOI: 10.1016/j.chom.2018.05.003. View

Bravo J, Forsythe P, Chew M, Escaravage E, Savignac H, Dinan T . Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci U S A. 2011; 108(38):16050-5. PMC: 3179073. DOI: 10.1073/pnas.1102999108. View

10.

Qu Y, Su C, Zhao Q, Shi A, Zhao F, Tang L . Gut Microbiota-Mediated Elevated Production of Secondary Bile Acids in Chronic Unpredictable Mild Stress. Front Pharmacol. 2022; 13:837543. PMC: 8936594. DOI: 10.3389/fphar.2022.837543. View

11.

Gao L, Liu X, Yu L, Wu J, Xu M, Liu Y . Folic acid exerts antidepressant effects by upregulating brain-derived neurotrophic factor and glutamate receptor 1 expression in brain. Neuroreport. 2017; 28(16):1078-1084. DOI: 10.1097/WNR.0000000000000887. View

12.

Bercik P . The microbiota-gut-brain axis: learning from intestinal bacteria?. Gut. 2011; 60(3):288-9. DOI: 10.1136/gut.2010.226779. View

13.

Baiao R, Capitao L, Higgins C, Browning M, Harmer C, Burnet P . Multispecies probiotic administration reduces emotional salience and improves mood in subjects with moderate depression: a randomised, double-blind, placebo-controlled study. Psychol Med. 2022; 53(8):3437-3447. PMC: 10277723. DOI: 10.1017/S003329172100550X. View

14.

Macpherson A, Harris N . Interactions between commensal intestinal bacteria and the immune system. Nat Rev Immunol. 2004; 4(6):478-85. DOI: 10.1038/nri1373. View

15.

Bonaz B, Sinniger V, Pellissier S . The Vagus Nerve in the Neuro-Immune Axis: Implications in the Pathology of the Gastrointestinal Tract. Front Immunol. 2017; 8:1452. PMC: 5673632. DOI: 10.3389/fimmu.2017.01452. View

16.

Russell D . The enzymes, regulation, and genetics of bile acid synthesis. Annu Rev Biochem. 2003; 72:137-74. DOI: 10.1146/annurev.biochem.72.121801.161712. View

17.

Miyaoka T, Kanayama M, Wake R, Hashioka S, Hayashida M, Nagahama M . Clostridium butyricum MIYAIRI 588 as Adjunctive Therapy for Treatment-Resistant Major Depressive Disorder: A Prospective Open-Label Trial. Clin Neuropharmacol. 2018; 41(5):151-155. DOI: 10.1097/WNF.0000000000000299. View

18.

Yu Y, Villalobos-Hernandez E, Pradhananga S, Baker C, Keating C, Grundy D . Deoxycholic acid activates colonic afferent nerves via 5-HT receptor-dependent and -independent mechanisms. Am J Physiol Gastrointest Liver Physiol. 2019; 317(3):G275-G284. DOI: 10.1152/ajpgi.00016.2019. View

19.

McCoy C, Rana S, Stringfellow S, Day J, Wyss J, Clinton S . Neonatal maternal separation stress elicits lasting DNA methylation changes in the hippocampus of stress-reactive Wistar Kyoto rats. Eur J Neurosci. 2016; 44(10):2829-2845. PMC: 5656998. DOI: 10.1111/ejn.13404. View

20.

Bonaz B, Bazin T, Pellissier S . The Vagus Nerve at the Interface of the Microbiota-Gut-Brain Axis. Front Neurosci. 2018; 12:49. PMC: 5808284. DOI: 10.3389/fnins.2018.00049. View