Hostname: page-component-848d4c4894-5nwft Total loading time: 0 Render date: 2024-06-12T16:39:30.260Z Has data issue: false hasContentIssue false

Shotgun metagenomics reveals both taxonomic and tryptophan pathway differences of gut microbiota in major depressive disorder patients

Published online by Cambridge University Press:  05 November 2019

Wen-tao Lai
Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China
Wen-feng Deng
Laboratory of Brain Stimulation and Biological Psychiatry, Brain Function and Psychosomatic Medicine Institute, Second People's Hospital of Huizhou, Huizhou, Guangdong, China
Shu-xian Xu
Laboratory of Brain Stimulation and Biological Psychiatry, Brain Function and Psychosomatic Medicine Institute, Second People's Hospital of Huizhou, Huizhou, Guangdong, China
Jie Zhao
Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China
Dan Xu
Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China
Yang-hui Liu
Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China
Yuan-yuan Guo
Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China
Ming-bang Wang
Xiamen Branch, Shanghai Key Laboratory of Birth Defects, Division of Neonatology, Children's Hospital of Fudan University, National Center for Children's Health, Shanghai, China
Fu-sheng He
Imunobio, Shenzhen, Guangdong, China
Shu-wei Ye
Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China
Qi-fan Yang
Laboratory of Brain Stimulation and Biological Psychiatry, Brain Function and Psychosomatic Medicine Institute, Second People's Hospital of Huizhou, Huizhou, Guangdong, China
Tie-bang Liu
Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China
Ying-li Zhang
Department of Depression, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China
Sheng Wang
Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China
Min-zhi Li
Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China
Ying-jia Yang
Department of Depression, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China
Xin-hui Xie*
Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China Laboratory of Brain Stimulation and Biological Psychiatry, Brain Function and Psychosomatic Medicine Institute, Second People's Hospital of Huizhou, Huizhou, Guangdong, China Center of Acute Psychiatry Service, Second People's Hospital of Huizhou, Huizhou, Guangdong, China
Han Rong
Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China Affiliated Shenzhen Clinical College of Psychiatry, Jining Medical University, Jining, Shandong, China
Authors for correspondence: Xin-hui Xie, E-mail:; Han Rong, E-mail:



The microbiota–gut–brain axis, especially the microbial tryptophan (Trp) biosynthesis and metabolism pathway (MiTBamp), may play a critical role in the pathogenesis of major depressive disorder (MDD). However, studies on the MiTBamp in MDD are lacking. The aim of the present study was to analyze the gut microbiota composition and the MiTBamp in MDD patients.


We performed shotgun metagenomic sequencing of stool samples from 26 MDD patients and 29 healthy controls (HCs). In addition to the microbiota community and the MiTBamp analyses, we also built a classification based on the Random Forests (RF) and Boruta algorithm to identify the gut microbiota as biomarkers for MDD.


The Bacteroidetes abundance was strongly reduced whereas that of Actinobacteria was significantly increased in the MDD patients compared with the abundance in the HCs. Most noteworthy, the MDD patients had increased levels of Bifidobacterium, which is commonly used as a probiotic. Four Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologies (KOs) (K01817, K11358, K01626, K01667) abundances in the MiTBamp were significantly lower in the MDD group. Furthermore, we found a negative correlation between the K01626 abundance and the HAMD scores in the MDD group. Finally, RF classification at the genus level can achieve an area under the receiver operating characteristic curve of 0.890.


The present findings enabled a better understanding of the changes in gut microbiota and the related Trp pathway in MDD. Alterations of the gut microbiota may have the potential as biomarkers for distinguishing MDD patients form HCs.

Original Articles
Copyright © Cambridge University Press 2019

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)


The first three authors, Wen-tao Lai, Wen-feng Deng, and Shu-xian Xu contributed equally to this paper.


Afgan, E, Baker, D, Batut, B, van den Beek, M, Bouvier, D, Cech, M, Chilton, J, Clements, D, Coraor, N, Gruning, BA, Guerler, A, Hillman-Jackson, J, Hiltemann, S, Jalili, V, Rasche, H, Soranzo, N, Goecks, J, Taylor, J, Nekrutenko, A and Blankenberg, D (2018) The Galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2018 update. Nucleic Acids Research 46, W537W544.CrossRefGoogle ScholarPubMed
Agus, A, Planchais, J and Sokol, H (2018) Gut microbiota regulation of tryptophan metabolism in health and disease. Cell Host & Microbe 23, 716724.CrossRefGoogle ScholarPubMed
Aizawa, E, Tsuji, H, Asahara, T, Takahashi, T, Teraishi, T, Yoshida, S, Ota, M, Koga, N, Hattori, K and Kunugi, H (2016) Possible association of Bifidobacterium and Lactobacillus in the gut microbiota of patients with major depressive disorder. Journal of Affective Disorders 202, 254257.CrossRefGoogle ScholarPubMed
Akkasheh, G, Kashani-Poor, Z, Tajabadi-Ebrahimi, M, Jafari, P, Akbari, H, Taghizadeh, M, Memarzadeh, MR, Asemi, Z and Esmaillzadeh, A (2016) Clinical and metabolic response to probiotic administration in patients with major depressive disorder: a randomized, double-blind, placebo-controlled trial. Nutrition 32, 315320.CrossRefGoogle ScholarPubMed
Alexeev, EE, Lanis, JM, Kao, DJ, Campbell, EL, Kelly, CJ, Battista, KD, Gerich, ME, Jenkins, BR, Walk, ST, Kominsky, DJ and Colgan, SP (2018) Microbiota-derived indole metabolites promote human and murine intestinal homeostasis through regulation of interleukin-10 receptor. The American Journal of Pathology 188, 11831194.CrossRefGoogle ScholarPubMed
American Psychiatric Association (2013) Diagnostic and Statistical Manual of Mental Disorders (DSM-5®). Philadelphia: American Psychiatric Pub.Google Scholar
Angst, J, Adolfsson, R, Benazzi, F, Gamma, A, Hantouche, E, Meyer, TD, Skeppar, P, Vieta, E and Scott, J (2005) The HCL-32: towards a self-assessment tool for hypomanic symptoms in outpatients. Journal of Affective Disorders 88, 217233.CrossRefGoogle ScholarPubMed
Bambury, A, Sandhu, K, Cryan, JF and Dinan, TG (2018) Finding the needle in the haystack: systematic identification of psychobiotics. British Journal of Pharmacology 175, 44304438.CrossRefGoogle ScholarPubMed
Benjamini, Y and Hochberg, Y (1995) Controlling the false discovery rate – a practical and powerful approach to multiple testing. Journal of the Royal Statistical Society. Series B: Methodological 57, 289300.Google Scholar
Bercik, P, Denou, E, Collins, J, Jackson, W, Lu, J, Jury, J, Deng, Y, Blennerhassett, P, Macri, J, McCoy, KD, Verdu, EF and Collins, SM (2011) The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. Gastroenterology 141, 599609.CrossRefGoogle ScholarPubMed
Bonvicini, C, Minelli, A, Scassellati, C, Bortolomasi, M, Segala, M, Sartori, R, Giacopuzzi, M and Gennarelli, M (2010) Serotonin transporter gene polymorphisms and treatment-resistant depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry 34, 934939.CrossRefGoogle ScholarPubMed
Booij, L, Van der Does, W, Benkelfat, C, Bremner, JD, Cowen, PJ, Fava, M, Gillin, C, Leyton, M, Moore, P, Smith, KA and Van der Kloot, WA (2002) Predictors of mood response to acute tryptophan depletion. A reanalysis. Neuropsychopharmacology 27, 852861.CrossRefGoogle ScholarPubMed
Bradley, AP (1997) The use of the area under the ROC curve in the evaluation of machine learning algorithms. Pattern Recognition 30, 11451159.CrossRefGoogle Scholar
Bravo, JA, Julio-Pieper, M, Forsythe, P, Kunze, W, Dinan, TG, Bienenstock, J and Cryan, JF (2012) Communication between gastrointestinal bacteria and the nervous system. Current Opinion in Pharmacology 12, 667672.CrossRefGoogle ScholarPubMed
Breiman, L (2001) Random forests. Machine Learning 45, 532.CrossRefGoogle Scholar
Bruce-Keller, AJ, Salbaum, JM and Berthoud, HR (2018) Harnessing gut microbes for mental health: getting from here to there. Biological Psychiatry 83, 214223.CrossRefGoogle Scholar
Butler, MI, Cryan, JF and Dinan, TG (2019) Man and the microbiome: a new theory of everything? Annual Review of Clinical Psychology 15, 371398.CrossRefGoogle Scholar
Cani, PD (2018) Human gut microbiome: hopes, threats and promises. Gut 67, 17161725.CrossRefGoogle ScholarPubMed
Chen, X and Ishwaran, H (2012) Random forests for genomic data analysis. Genomics 99, 323329.CrossRefGoogle ScholarPubMed
Chen, Z, Li, J, Gui, S, Zhou, C, Chen, J, Yang, C, Hu, Z, Wang, H, Zhong, X, Zeng, L, Chen, K, Li, P and Xie, P (2018) Comparative metaproteomics analysis shows altered fecal microbiota signatures in patients with major depressive disorder. Neuroreport 29, 417425.CrossRefGoogle ScholarPubMed
Chen, L, Chen, DQ, Liu, JR, Zhang, J, Vaziri, ND, Zhuang, S, Chen, H, Feng, YL, Guo, Y and Zhao, YY (2019) Unilateral ureteral obstruction causes gut microbial dysbiosis and metabolome disorders contributing to tubulointerstitial fibrosis. Experimental & Molecular Medicine 51, 38.CrossRefGoogle ScholarPubMed
Cheung, SG, Goldenthal, AR, Uhlemann, AC, Mann, JJ, Miller, JM and Sublette, ME (2019) Systematic review of gut microbiota and major depression. Frontiers in Psychiatry 10, 34.CrossRefGoogle ScholarPubMed
Cicchetti, DV (2001) The precision of reliability and validity estimates re-visited: distinguishing between clinical and statistical significance of sample size requirements. Journal of Clinical & Experimental Neuropsychology 23, 695700.CrossRefGoogle ScholarPubMed
Collins, SM and Bercik, P (2009) The relationship between intestinal microbiota and the central nervous system in normal gastrointestinal function and disease. Gastroenterology 136, 20032014.CrossRefGoogle ScholarPubMed
Cryan, JF and Dinan, TG (2012) Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nature Reviews. Neuroscience 13, 701712.CrossRefGoogle ScholarPubMed
Cryan, JF and O'Mahony, SM (2011) The microbiome-gut-brain axis: from bowel to behavior. Neurogastroenterology and Motility 23, 187192.CrossRefGoogle Scholar
Dash, S, Clarke, G, Berk, M and Jacka, FN (2015) The gut microbiome and diet in psychiatry: focus on depression. Current Opinion in Psychiatry 28, 16.CrossRefGoogle ScholarPubMed
De Palma, G, Lynch, MD, Lu, J, Dang, VT, Deng, Y, Jury, J, Umeh, G, Miranda, PM, Pigrau Pastor, M, Sidani, S, Pinto-Sanchez, MI, Philip, V, McLean, PG, Hagelsieb, MG, Surette, MG, Bergonzelli, GE, Verdu, EF, Britz-McKibbin, P, Neufeld, JD, Collins, SM and Bercik, P (2017) Transplantation of fecal microbiota from patients with irritable bowel syndrome alters gut function and behavior in recipient mice. Science Translational Medicine 9, eaaf6397.CrossRefGoogle ScholarPubMed
de Roos, NM and Katan, MB (2000) Effects of probiotic bacteria on diarrhea, lipid metabolism, and carcinogenesis: a review of papers published between 1988 and 1998. The American Journal of Clinical Nutrition 71, 405411.CrossRefGoogle ScholarPubMed
DeMyer, MK, Shea, PA, Hendrie, HC and Yoshimura, NN (1981) Plasma tryptophan and five other amino acids in depressed and normal subjects. Archives of General Psychiatry 38, 642646.CrossRefGoogle ScholarPubMed
Dhariwal, A, Chong, J, Habib, S, King, IL, Agellon, LB and Xia, J (2017) Microbiomeanalyst: a web-based tool for comprehensive statistical, visual and meta-analysis of microbiome data. Nucleic Acids Research 45, W180W188.CrossRefGoogle ScholarPubMed
Di Giaimo, R, Durovic, T, Barquin, P, Kociaj, A, Lepko, T, Aschenbroich, S, Breunig, CT, Irmler, M, Cernilogar, FM, Schotta, G, Barbosa, JS, Trumbach, D, Baumgart, EV, Neuner, AM, Beckers, J, Wurst, W, Stricker, SH and Ninkovic, J (2018) The aryl hydrocarbon receptor pathway defines the time frame for restorative neurogenesis. Cell Reports 25, 32413251.CrossRefGoogle ScholarPubMed
Dickerson, F, Severance, E and Yolken, R (2017) The microbiome, immunity, and schizophrenia and bipolar disorder. Brain, Behavior, and Immunity 62, 4652.CrossRefGoogle ScholarPubMed
Dinan, TG and Cryan, JF (2017) Gut-brain axis in 2016: brain-gut-microbiota axis – mood, metabolism and behaviour. Nature Reviews Gastroenterology & Hepatology 14, 6970.CrossRefGoogle ScholarPubMed
Dinan, TG, Stanton, C and Cryan, JF (2013) Psychobiotics: a novel class of psychotropic. Biological Psychiatry 74, 720726.CrossRefGoogle ScholarPubMed
Doolin, K, Allers, KA, Pleiner, S, Liesener, A, Farrell, C, Tozzi, L, O'Hanlon, E, Roddy, D, Frodl, T, Harkin, A and O'Keane, V (2018) Altered tryptophan catabolite concentrations in major depressive disorder and associated changes in hippocampal subfield volumes. Psychoneuroendocrinology 95, 817.CrossRefGoogle ScholarPubMed
Fakhoury, M (2016) Revisiting the serotonin hypothesis: implications for major depressive disorders. Molecular Neurobiology 53, 27782786.CrossRefGoogle ScholarPubMed
First, MB and Williams, JB (2016) SCID-5-CV: Structured Clinical Interview for DSM-5 Disorders: Clinician Version. Philadelphia: American Psychiatric Association Publishing.Google Scholar
Forbes, JD, Chen, CY, Knox, NC, Marrie, RA, El-Gabalawy, H, de Kievit, T, Alfa, M, Bernstein, CN and Van Domselaar, G (2018) A comparative study of the gut microbiota in immune-mediated inflammatory diseases-does a common dysbiosis exist? Microbiome 6, 221.CrossRefGoogle ScholarPubMed
Forsythe, P, Bienenstock, J and Kunze, WA (2014) Vagal pathways for microbiome-brain-gut axis communication. Advances in Experimental Medicine and Biology 817, 115133.CrossRefGoogle ScholarPubMed
Foster, JA and McVey Neufeld, K-A (2013) Gut–brain axis: how the microbiome influences anxiety and depression. Trends in Neurosciences 36, 305312.CrossRefGoogle ScholarPubMed
Franz, CM, Holzapfel, WH and Stiles, ME (1999) Enterococci at the crossroads of food safety? International Journal of Food Microbiology 47, 124.CrossRefGoogle ScholarPubMed
Franzosa, EA, Hsu, T, Sirota-Madi, A, Shafquat, A, Abu-Ali, G, Morgan, XC and Huttenhower, C (2015) Sequencing and beyond: integrating molecular ‘omics’ for microbial community profiling. Nature Reviews Microbiology 13, 360372.CrossRefGoogle Scholar
Gauthier, C, Hassler, C, Mattar, L, Launay, JM, Callebert, J, Steiger, H, Melchior, JC, Falissard, B, Berthoz, S, Mourier-Soleillant, V, Lang, F, Delorme, M, Pommereau, X, Gerardin, P, Bioulac, S, Bouvard, M, Group, E and Godart, N (2014) Symptoms of depression and anxiety in anorexia nervosa: links with plasma tryptophan and serotonin metabolism. Psychoneuroendocrinology 39, 170178.CrossRefGoogle ScholarPubMed
González-Flores, D, Belén, V, Garrido, M, Gonzalez-Gomez, D, Lozano, M, Ayuso, M, Barriga, C, Paredes, S and Rodriguez, A (2011) Ingestion of Japanese plums (Prunus salicina Lindl. cv. Crimson Globe) increases the urinary 6 sulfatoxymelatonin and total antioxidant capacity levels in young, middle-aged and elderly humans: nutritional and functional characterization of their content. Journal of Food & Nutrition Research 50, 229236.Google Scholar
Gough, EK, Stephens, DA, Moodie, EE, Prendergast, AJ, Stoltzfus, RJ, Humphrey, JH and Manges, AR (2015) Linear growth faltering in infants is associated with Acidaminococcus sp. and community-level changes in the gut microbiota. Microbiome 3, 24.CrossRefGoogle ScholarPubMed
Groen, RN, de Clercq, NC, Nieuwdorp, M, Hoenders, HJR and Groen, AK (2018) Gut microbiota, metabolism and psychopathology: a critical review and novel perspectives. Critical Reviews in Clinical Laboratory Sciences 55, 283293.CrossRefGoogle ScholarPubMed
Hamilton, M (1959) The assessment of anxiety states by rating. British Journal of Medical Psychology 32, 5055.CrossRefGoogle ScholarPubMed
Hamilton, M (1960) A rating scale for depression. Journal of Neurology, Neurosurgery, and Psychiatry 23, 5662.CrossRefGoogle ScholarPubMed
Hayley, S, Audet, MC and Anisman, H (2016) Inflammation and the microbiome: implications for depressive disorders. Current Opinion in Pharmacology 29, 4246.CrossRefGoogle ScholarPubMed
Hong, WD, Dong, LM, Jiang, ZC, Zhu, QH and Jin, SQ (2011) Prediction of large esophageal varices in cirrhotic patients using classification and regression tree analysis. Clinics 66, 119124.CrossRefGoogle ScholarPubMed
Hooks, KB, Konsman, JP and O'Malley, MA (2018) Microbiota-gut-brain research: a critical analysis. Behavioral and Brain Sciences 42, E60.CrossRefGoogle Scholar
Hsiao, CY, Tsai, HC, Chi, MH, Chen, KC, Chen, PS, Lee, IH, Yeh, TL and Yang, YK (2016) The association between baseline subjective anxiety rating and changes in cardiac autonomic nervous activity in response to tryptophan depletion in healthy volunteers. Medicine 95, e3498.CrossRefGoogle ScholarPubMed
Hubbard, TD, Murray, IA and Perdew, GH (2015) Indole and tryptophan metabolism: endogenous and dietary routes to Ah receptor activation. Drug Metabolism and Disposition 43, 15221535.CrossRefGoogle ScholarPubMed
Huson, DH, Auch, AF, Qi, J and Schuster, SC (2007) MEGAN analysis of metagenomic data. Genome Research 17, 377386.CrossRefGoogle ScholarPubMed
Jiang, H, Ling, Z, Zhang, Y, Mao, H, Ma, Z, Yin, Y, Wang, W, Tang, W, Tan, Z, Shi, J, Li, L and Ruan, B (2015) Altered fecal microbiota composition in patients with major depressive disorder. Brain, Behavior, and Immunity 48, 186194.CrossRefGoogle ScholarPubMed
Kaluzna-Czaplinska, J and Blaszczyk, S (2012) The level of arabinitol in autistic children after probiotic therapy. Nutrition 28, 124126.CrossRefGoogle ScholarPubMed
Kanehisa, M and Goto, S (2000) KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Research 28, 2730.CrossRefGoogle ScholarPubMed
Karg, K, Burmeister, M, Shedden, K and Sen, S (2011) The serotonin transporter promoter variant (5-HTTLPR), stress, and depression meta-analysis revisited: evidence of genetic moderation. Archives of General Psychiatry 68, 444454.CrossRefGoogle ScholarPubMed
Kazemi, A, Noorbala, AA, Azam, K, Eskandari, MH and Djafarian, K (2019) Effect of probiotic and prebiotic vs placebo on psychological outcomes in patients with major depressive disorder: a randomized clinical trial. Clinical Nutrition 38, 522528.CrossRefGoogle ScholarPubMed
Kelly, JR, Borre, Y, O'Brien, C, Patterson, E, El Aidy, S, Deane, J, Kennedy, PJ, Beers, S, Scott, K, Moloney, G, Hoban, AE, Scott, L, Fitzgerald, P, Ross, P, Stanton, C, Clarke, G, Cryan, JF and Dinan, TG (2016) Transferring the blues: depression-associated gut microbiota induces neurobehavioural changes in the rat. Journal of Psychiatric Research 82, 109118.CrossRefGoogle ScholarPubMed
Kiecolt-Glaser, JK, Derry, HM and Fagundes, CP (2015) Inflammation: depression fans the flames and feasts on the heat. American Journal of Psychiatry 172, 10751091.CrossRefGoogle ScholarPubMed
Kim, YK, Na, KS, Myint, AM and Leonard, BE (2016) The role of pro-inflammatory cytokines in neuroinflammation, neurogenesis and the neuroendocrine system in major depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry 64, 277284.CrossRefGoogle ScholarPubMed
Kim, D, Hofstaedter, CE, Zhao, C, Mattei, L, Tanes, C, Clarke, E, Lauder, A, Sherrill-Mix, S, Chehoud, C, Kelsen, J, Conrad, M, Collman, RG, Baldassano, R, Bushman, FD and Bittinger, K (2017) Optimizing methods and dodging pitfalls in microbiome research. Microbiome 5, 52.CrossRefGoogle ScholarPubMed
Kiseleva, EP, Mikhailopulo, KI, Sviridov, OV, Novik, GI, Knirel, YA and Szwajcer Dey, E (2011) The role of components of Bifidobacterium and Lactobacillus in pathogenesis and serologic diagnosis of autoimmune thyroid diseases. Beneficial Microbes 2, 139154.CrossRefGoogle ScholarPubMed
Kiseleva, EP, Mikhailopulo, KI, Novik, GI, Szwajcer Dey, E, Zdorovenko, EL, Shashkov, AS and Knirel, YA (2013) Isolation and structural identification of glycopolymers of Bifidobacterium bifidum BIM B-733D as putative players in pathogenesis of autoimmune thyroid diseases. Beneficial Microbes 4, 375391.CrossRefGoogle ScholarPubMed
Kohler, S, Cierpinsky, K, Kronenberg, G and Adli, M (2016) The serotonergic system in the neurobiology of depression: relevance for novel antidepressants. Journal of Psychopharmacology 30, 1322.CrossRefGoogle ScholarPubMed
Kraus, C, Castren, E, Kasper, S and Lanzenberger, R (2017) Serotonin and neuroplasticity – links between molecular, functional and structural pathophysiology in depression. Neuroscience & Biobehavioral Reviews 77, 317326.CrossRefGoogle ScholarPubMed
Kursa, MB and Rudnicki, WR (2010) Feature selection with the Boruta package. Journal of Statistical Software 36, 113.CrossRefGoogle Scholar
Lam, YY, Ha, CW, Campbell, CR, Mitchell, AJ, Dinudom, A, Oscarsson, J, Cook, DI, Hunt, NH, Caterson, ID, Holmes, AJ and Storlien, LH (2012) Increased gut permeability and microbiota change associate with mesenteric fat inflammation and metabolic dysfunction in diet-induced obese mice. PLoS ONE 7, e34233.CrossRefGoogle ScholarPubMed
Lam, YY, Zhang, C and Zhao, L (2018) Causality in dietary interventions-building a case for gut microbiota. Genome Medicine 10, 62.CrossRefGoogle ScholarPubMed
Lamas, B, Natividad, JM and Sokol, H (2018) Aryl hydrocarbon receptor and intestinal immunity. Mucosal Immunology 11, 10241038.CrossRefGoogle ScholarPubMed
Latchney, SE, Hein, AM, O'Banion, MK, DiCicco-Bloom, E and Opanashuk, LA (2013) Deletion or activation of the aryl hydrocarbon receptor alters adult hippocampal neurogenesis and contextual fear memory. Journal of Neurochemistry 125, 430445.CrossRefGoogle ScholarPubMed
Leroi, AM, Lalaude, O, Antonietti, M, Touchais, JY, Ducrotte, P, Menard, JF and Denis, P (2000) Prolonged stationary colonic motility recording in seven patients with severe constipation secondary to antidepressants. Neurogastroenterology and Motility 12, 149154.CrossRefGoogle Scholar
Li, B, Evivie, SE, Jin, D, Meng, Y, Li, N, Yan, F, Huo, G and Liu, F (2018) Complete genome sequence of Enterococcus durans KLDS6.0933, a potential probiotic strain with high cholesterol removal ability. Gut Pathogens 10, 32.CrossRefGoogle ScholarPubMed
Lin, P, Ding, B, Feng, C, Yin, S, Zhang, T, Qi, X, Lv, H, Guo, X, Dong, K, Zhu, Y and Li, Q (2017) Prevotella and Klebsiella proportions in fecal microbial communities are potential characteristic parameters for patients with major depressive disorder. Journal of Affective Disorders 207, 300304.CrossRefGoogle ScholarPubMed
Ling, CX, Huang, J and Zhang, H (2003) AUC: a better measure than accuracy in comparing learning algorithms. In Xiang, Y and Chaib-draa, B (eds), Conference of the Canadian Society for Computational Studies of Intelligence. Berlin, Heidelberg: Springer, pp. 329341.Google Scholar
Loh, WY (2012) Variable selection for classification and regression in large p, small n problems. In Barbour A, Chan HP and Siegmund D (eds), Probability Approximations and Beyond. New York, NY: Springer, pp. 135159.CrossRefGoogle Scholar
Lynch, SV and Pedersen, O (2016) The human intestinal microbiome in health and disease. New England Journal of Medicine 375, 23692379.CrossRefGoogle ScholarPubMed
Mahar, I, Bambico, FR, Mechawar, N and Nobrega, JN (2014) Stress, serotonin, and hippocampal neurogenesis in relation to depression and antidepressant effects. Neuroscience & Biobehavioral Reviews 38, 173192.CrossRefGoogle ScholarPubMed
Manzella, C, Singhal, M, Alrefai, WA, Saksena, S, Dudeja, PK and Gill, RK (2018) Serotonin is an endogenous regulator of intestinal CYP1A1 via AhR. Scientific Reports 8, 6103.CrossRefGoogle ScholarPubMed
Mawe, GM and Hoffman, JM (2013) Serotonin signalling in the gut – functions, dysfunctions and therapeutic targets. Nature Reviews Gastroenterology & Hepatology 10, 473486.CrossRefGoogle ScholarPubMed
Messaoudi, M, Lalonde, R, Violle, N, Javelot, H, Desor, D, Nejdi, A, Bisson, JF, Rougeot, C, Pichelin, M, Cazaubiel, M and Cazaubiel, JM (2011 a) Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. British Journal of Nutrition 105, 755764.CrossRefGoogle ScholarPubMed
Messaoudi, M, Violle, N, Bisson, JF, Desor, D, Javelot, H and Rougeot, C (2011 b) Beneficial psychological effects of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in healthy human volunteers. Gut Microbes 2, 256261.CrossRefGoogle Scholar
Metidji, A, Omenetti, S, Crotta, S, Li, Y, Nye, E, Ross, E, Li, V, Maradana, MR, Schiering, C and Stockinger, B (2018) The environmental sensor AHR protects from inflammatory damage by maintaining intestinal stem cell homeostasis and barrier integrity. Immunity 49, 353362.CrossRefGoogle ScholarPubMed
Miller, AH and Raison, CL (2016) The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nature Reviews Immunology 16, 2234.CrossRefGoogle Scholar
Munoz-Bellido, JL, Munoz-Criado, S and Garcia-Rodriguez, JA (2000) Antimicrobial activity of psychotropic drugs: selective serotonin reuptake inhibitors. International Journal of Antimicrobial Agents 14, 177180.CrossRefGoogle ScholarPubMed
Naseribafrouei, A, Hestad, K, Avershina, E, Sekelja, M, Linlokken, A, Wilson, R and Rudi, K (2014) Correlation between the human fecal microbiota and depression. Neurogastroenterology and Motility 26, 11551162.CrossRefGoogle ScholarPubMed
Natividad, JM, Agus, A, Planchais, J, Lamas, B, Jarry, AC, Martin, R, Michel, ML, Chong-Nguyen, C, Roussel, R, Straube, M, Jegou, S, McQuitty, C, Le Gall, M, da Costa, G, Lecornet, E, Michaudel, C, Modoux, M, Glodt, J, Bridonneau, C, Sovran, B, Dupraz, L, Bado, A, Richard, ML, Langella, P, Hansel, B, Launay, JM, Xavier, RJ, Duboc, H and Sokol, H (2018) Impaired aryl hydrocarbon receptor ligand production by the gut microbiota is a key factor in metabolic syndrome. Cell Metabolism 28, 737749.CrossRefGoogle ScholarPubMed
Natori, Y, Kano, Y and Imamoto, F (1990) Nucleotide sequences and genomic constitution of five tryptophan genes of Lactobacillus casei. The Journal of Biochemistry 107, 248255.CrossRefGoogle ScholarPubMed
O'Mahony, SM, Clarke, G, Borre, YE, Dinan, TG and Cryan, JF (2015) Serotonin, tryptophan metabolism and the brain-gut-microbiome axis. Behavioural Brain Research 277, 3248.CrossRefGoogle ScholarPubMed
Ogawa, S, Fujii, T, Koga, N, Hori, H, Teraishi, T, Hattori, K, Noda, T, Higuchi, T, Motohashi, N and Kunugi, H (2014) Plasma L-tryptophan concentration in major depressive disorder: new data and meta-analysis. The Journal of Clinical Psychiatry 75, e906e915.CrossRefGoogle ScholarPubMed
Ogawa, S, Koga, N, Hattori, K, Matsuo, J, Ota, M, Hori, H, Sasayama, D, Teraishi, T, Ishida, I, Yoshida, F, Yoshida, S, Noda, T, Higuchi, T and Kunugi, H (2018) Plasma amino acid profile in major depressive disorder: analyses in two independent case-control sample sets. Journal of Psychiatric Research 96, 2332.CrossRefGoogle ScholarPubMed
Pamer, C, Serpi, T and Finkelstein, J (2008) Analysis of Maryland poisoning deaths using classification and regression tree (CART) analysis. AMIA Annual Symposium Proceedings, pp. 550554.Google Scholar
Paulson, JN, Stine, OC, Bravo, HC and Pop, M (2013) Differential abundance analysis for microbial marker-gene surveys. Nature Methods 10, 12001202.CrossRefGoogle ScholarPubMed
Qin, J, Li, Y, Cai, Z, Li, S, Zhu, J, Zhang, F, Liang, S, Zhang, W, Guan, Y, Shen, D, Peng, Y, Zhang, D, Jie, Z, Wu, W, Qin, Y, Xue, W, Li, J, Han, L, Lu, D, Wu, P, Dai, Y, Sun, X, Li, Z, Tang, A, Zhong, S, Li, X, Chen, W, Xu, R, Wang, M, Feng, Q, Gong, M, Yu, J, Zhang, Y, Zhang, M, Hansen, T, Sanchez, G, Raes, J, Falony, G, Okuda, S, Almeida, M, LeChatelier, E, Renault, P, Pons, N, Batto, JM, Zhang, Z, Chen, H, Yang, R, Zheng, W, Li, S, Yang, H, Wang, J, Ehrlich, SD, Nielsen, R, Pedersen, O, Kristiansen, K and Wang, J (2012) A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490, 5560.CrossRefGoogle ScholarPubMed
Ridaura, VK, Faith, JJ, Rey, FE, Cheng, J, Duncan, AE, Kau, AL, Griffin, NW, Lombard, V, Henrissat, B, Bain, JR, Muehlbauer, MJ, Ilkayeva, O, Semenkovich, CF, Funai, K, Hayashi, DK, Lyle, BJ, Martini, MC, Ursell, LK, Clemente, JC, Van Treuren, W, Walters, WA, Knight, R, Newgard, CB, Heath, AC and Gordon, JI (2013) Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 341, 1241214.CrossRefGoogle ScholarPubMed
Rieder, R, Wisniewski, PJ, Alderman, BL and Campbell, SC (2017) Microbes and mental health: a review. Brain, Behavior, and Immunity 66, 917.CrossRefGoogle ScholarPubMed
Robinson, OJ, Overstreet, C, Allen, PS, Pine, DS and Grillon, C (2012) Acute tryptophan depletion increases translational indices of anxiety but not fear: serotonergic modulation of the bed nucleus of the stria terminalis? Neuropsychopharmacology 37, 19631971.CrossRefGoogle Scholar
Rogers, GB, Keating, DJ, Young, RL, Wong, ML, Licinio, J and Wesselingh, S (2016) From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways. Molecular Psychiatry 21, 738748.CrossRefGoogle ScholarPubMed
Rong, H, Xie, XH, Zhao, J, Lai, WT, Wang, MB, Xu, D, Liu, YH, Guo, YY, Xu, SX, Deng, WF, Yang, QF, Xiao, L, Zhang, YL, He, FS, Wang, S and Liu, TB (2019) Similarly in depression, nuances of gut microbiota: evidences from a shotgun metagenomics sequencing study on major depressive disorder versus bipolar disorder with current major depressive episode patients. Journal of Psychiatric Research 113, 9099.CrossRefGoogle Scholar
Rothhammer, V and Quintana, FJ (2019) The aryl hydrocarbon receptor: an environmental sensor integrating immune responses in health and disease. Nature Reviews. Immunology 19, 184197.CrossRefGoogle ScholarPubMed
Rothhammer, V, Mascanfroni, ID, Bunse, L, Takenaka, MC, Kenison, JE, Mayo, L, Chao, CC, Patel, B, Yan, R, Blain, M, Alvarez, JI, Kebir, H, Anandasabapathy, N, Izquierdo, G, Jung, S, Obholzer, N, Pochet, N, Clish, CB, Prinz, M, Prat, A, Antel, J and Quintana, FJ (2016) Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor. Nature Medicine 22, 586597.CrossRefGoogle ScholarPubMed
Rothhammer, V, Borucki, DM, Tjon, EC, Takenaka, MC, Chao, CC, Ardura-Fabregat, A, de Lima, KA, Gutierrez-Vazquez, C, Hewson, P, Staszewski, O, Blain, M, Healy, L, Neziraj, T, Borio, M, Wheeler, M, Dragin, LL, Laplaud, DA, Antel, J, Alvarez, JI, Prinz, M and Quintana, FJ (2018) Microglial control of astrocytes in response to microbial metabolites. Nature 557, 724728.CrossRefGoogle ScholarPubMed
Rudzki, L, Ostrowska, L, Pawlak, D, Malus, A, Pawlak, K, Waszkiewicz, N and Szulc, A (2019) Probiotic Lactobacillus Plantarum 299v decreases kynurenine concentration and improves cognitive functions in patients with major depression: a double-blind, randomized, placebo controlled study. Psychoneuroendocrinology 100, 213222.CrossRefGoogle ScholarPubMed
Salameh, A, Klotz, SA and Zangeneh, TT (2012) Disseminated infection caused by Eggerthella lenta in a previously healthy young man: a case report. Case Reports in Infectious Diseases 2012, 517637.CrossRefGoogle Scholar
Schiering, C, Wincent, E, Metidji, A, Iseppon, A, Li, Y, Potocnik, AJ, Omenetti, S, Henderson, CJ, Wolf, CR, Nebert, DW and Stockinger, B (2017) Feedback control of AHR signalling regulates intestinal immunity. Nature 542, 242245.CrossRefGoogle ScholarPubMed
Segata, N, Izard, J, Waldron, L, Gevers, D, Miropolsky, L, Garrett, WS and Huttenhower, C (2011) Metagenomic biomarker discovery and explanation. Genome Biology 12, R60.CrossRefGoogle ScholarPubMed
Shaaban, SY, El Gendy, YG, Mehanna, NS, El-Senousy, WM, El-Feki, HSA, Saad, K and El-Asheer, OM (2018) The role of probiotics in children with autism spectrum disorder: a prospective, open-label study. Nutritional Neuroscience 21, 676681.CrossRefGoogle ScholarPubMed
Sheehan, DV, Lecrubier, Y, Sheehan, KH, Amorim, P, Janavs, J, Weiller, E, Hergueta, T, Baker, R and Dunbar, GC (1998) The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. The Journal of Clinical Psychiatry 59(suppl. 20), 2233.Google ScholarPubMed
Sherwin, E, Sandhu, KV, Dinan, TG and Cryan, JF (2016) May the force be with you: the light and dark sides of the microbiota-gut-brain axis in neuropsychiatry. CNS Drugs 30, 10191041.CrossRefGoogle ScholarPubMed
Smits, SA, Leach, J, Sonnenburg, ED, Gonzalez, CG, Lichtman, JS, Reid, G, Knight, R, Manjurano, A, Changalucha, J, Elias, JE, Dominguez-Bello, MG and Sonnenburg, JL (2017) Seasonal cycling in the gut microbiome of the Hadza hunter-gatherers of Tanzania. Science 357, 802806.CrossRefGoogle ScholarPubMed
Snyder, JS, Soumier, A, Brewer, M, Pickel, J and Cameron, HA (2011) Adult hippocampal neurogenesis buffers stress responses and depressive behaviour. Nature 476, 458461.CrossRefGoogle ScholarPubMed
Stevens, BR, Goel, R, Seungbum, K, Richards, EM, Holbert, RC, Pepine, CJ and Raizada, MK (2018) Increased human intestinal barrier permeability plasma biomarkers zonulin and FABP2 correlated with plasma LPS and altered gut microbiome in anxiety or depression. Gut 67, 15551557.CrossRefGoogle ScholarPubMed
Strawbridge, R, Arnone, D, Danese, A, Papadopoulos, A, Herane Vives, A and Cleare, AJ (2015) Inflammation and clinical response to treatment in depression: a meta-analysis. European Neuropsychopharmacology 25, 15321543.CrossRefGoogle ScholarPubMed
Surget, A, Tanti, A, Leonardo, ED, Laugeray, A, Rainer, Q, Touma, C, Palme, R, Griebel, G, Ibarguen-Vargas, Y, Hen, R and Belzung, C (2011) Antidepressants recruit new neurons to improve stress response regulation. Molecular Psychiatry 16, 11771188.CrossRefGoogle ScholarPubMed
Tack, J, Broekaert, D, Corsetti, M, Fischler, B and Janssens, J (2006) Influence of acute serotonin reuptake inhibition on colonic sensorimotor function in man. Alimentary Pharmacology & Therapeutics 23, 265274.CrossRefGoogle ScholarPubMed
Thota, VR, Dacha, S, Natarajan, A and Nerad, J (2011) Eggerthella lenta bacteremia in a Crohn's disease patient after ileocecal resection. Future Microbiology 6, 595597.CrossRefGoogle Scholar
Tomova, A, Husarova, V, Lakatosova, S, Bakos, J, Vlkova, B, Babinska, K and Ostatnikova, D (2015) Gastrointestinal microbiota in children with autism in Slovakia. Physiology & Behavior 138, 179187.CrossRefGoogle ScholarPubMed
Valles-Colomer, M, Falony, G, Darzi, Y, Tigchelaar, EF, Wang, J, Tito, RY, Schiweck, C, Kurilshikov, A, Joossens, M, Wijmenga, C, Claes, S, Van Oudenhove, L, Zhernakova, A, Vieira-Silva, S and Raes, J (2019) The neuroactive potential of the human gut microbiota in quality of life and depression. Nature Microbiology 4, 623632.CrossRefGoogle ScholarPubMed
Vonaesch, P, Anderson, M and Sansonetti, PJ (2018) Pathogens, microbiome and the host: emergence of the ecological Koch's postulates. FEMS Microbiology Reviews 42, 273292.CrossRefGoogle ScholarPubMed
Vrieze, A, Van Nood, E, Holleman, F, Salojarvi, J, Kootte, RS, Bartelsman, JF, Dallinga-Thie, GM, Ackermans, MT, Serlie, MJ, Oozeer, R, Derrien, M, Druesne, A, Van Hylckama Vlieg, JE, Bloks, VW, Groen, AK, Heilig, HG, Zoetendal, EG, Stroes, ES, de Vos, WM, Hoekstra, JB and Nieuwdorp, M (2012) Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology 143, 913916.CrossRefGoogle ScholarPubMed
Wang, M, Wan, J, Rong, H, He, F, Wang, H, Zhou, J, Cai, C, Wang, Y, Xu, R, Yin, Z and Zhou, W (2019) Alterations in gut glutamate metabolism associated with changes in gut microbiota composition in children with autism spectrum disorder. mSystems 4, e00321e00318.CrossRefGoogle ScholarPubMed
Wen, C, Zheng, Z, Shao, T, Liu, L, Xie, Z, Le Chatelier, E, He, Z, Zhong, W, Fan, Y, Zhang, L, Li, H, Wu, C, Hu, C, Xu, Q, Zhou, J, Cai, S, Wang, D, Huang, Y, Breban, M, Qin, N and Ehrlich, SD (2017) Quantitative metagenomics reveals unique gut microbiome biomarkers in ankylosing spondylitis. Genome Biology 18, 142.CrossRefGoogle ScholarPubMed
Winter, G, Hart, RA, Charlesworth, RPG and Sharpley, CF (2018) Gut microbiome and depression: what we know and what we need to know. Reviews in the Neurosciences 29, 629643.CrossRefGoogle ScholarPubMed
Wohleb, ES, Franklin, T, Iwata, M and Duman, RS (2016) Integrating neuroimmune systems in the neurobiology of depression. Nature Reviews. Neuroscience 17, 497511.CrossRefGoogle ScholarPubMed
Xu, HB, Fang, L, Hu, ZC, Chen, YC, Chen, JJ, Li, FF, Lu, J, Mu, J and Xie, P (2012) Potential clinical utility of plasma amino acid profiling in the detection of major depressive disorder. Psychiatry Research 200, 10541057.CrossRefGoogle ScholarPubMed
Young, SL, Simon, MA, Baird, MA, Tannock, GW, Bibiloni, R, Spencely, K, Lane, JM, Fitzharris, P, Crane, J, Town, I, Addo-Yobo, E, Murray, CS and Woodcock, A (2004) Bifidobacterial species differentially affect expression of cell surface markers and cytokines of dendritic cells harvested from cord blood. Clinical and Diagnostic Laboratory Immunology 11, 686690.CrossRefGoogle ScholarPubMed
Yuan, X, Zhang, P, Wang, Y, Liu, Y, Li, X, Kumar, BU, Hei, G, Lv, L, Huang, XF, Fan, X and Song, X (2018) Changes in metabolism and microbiota after 24-week risperidone treatment in drug naive, normal weight patients with first episode schizophrenia. Schizophrenia Research 201, 299306.CrossRefGoogle ScholarPubMed
Zelante, T, Iannitti, RG, Cunha, C, De Luca, A, Giovannini, G, Pieraccini, G, Zecchi, R, D'Angelo, C, Massi-Benedetti, C, Fallarino, F, Carvalho, A, Puccetti, P and Romani, L (2013) Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity 39, 372385.CrossRefGoogle ScholarPubMed
Zhang, C, Zhang, W, Zhang, J, Jing, Y, Yang, M, Du, L, Gao, F, Gong, H, Chen, L, Li, J, Liu, H, Qin, C, Jia, Y, Qiao, J, Wei, B, Yu, Y, Zhou, H, Liu, Z, Yang, D and Li, J (2018) Gut microbiota dysbiosis in male patients with chronic traumatic complete spinal cord injury. Journal of Translational Medicine 16, 353.CrossRefGoogle ScholarPubMed
Zhao, L, Zhang, Q, Ma, W, Tian, F, Shen, H and Zhou, M (2017) A combination of quercetin and resveratrol reduces obesity in high-fat diet-fed rats by modulation of gut microbiota. Food & Function 8, 46444656.CrossRefGoogle ScholarPubMed
Zheng, P, Zeng, B, Zhou, C, Liu, M, Fang, Z, Xu, X, Zeng, L, Chen, J, Fan, S, Du, X, Zhang, X, Yang, D, Yang, Y, Meng, H, Li, W, Melgiri, ND, Licinio, J, Wei, H and Xie, P (2016) Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host's metabolism. Molecular Psychiatry 21, 786796.CrossRefGoogle ScholarPubMed
Zhou, S, Wang, Z, He, F, Qiu, H, Wang, Y, Wang, H, Zhou, J, Zhou, J, Cheng, G, Zhou, W, Xu, R and Wang, M (2019) Association of serum bilirubin in newborns affected by jaundice with gut microbiota dysbiosis. The Journal of Nutritional Biochemistry 63, 5461.CrossRefGoogle ScholarPubMed
Zmora, N, Suez, J and Elinav, E (2019) You are what you eat: diet, health and the gut microbiota. Nature Reviews. Gastroenterology & Hepatology 16, 3556.CrossRefGoogle ScholarPubMed
Supplementary material: File

Lai et al. supplementary material

Lai et al. supplementary material 1

Download Lai et al. supplementary material(File)
File 29.8 KB
Supplementary material: Image

Lai et al. supplementary material

Lai et al. supplementary material 2

Download Lai et al. supplementary material(Image)
Image 3.2 MB
Supplementary material: File

Lai et al. supplementary material

Lai et al. supplementary material 3

Download Lai et al. supplementary material(File)
File 66.2 KB
Supplementary material: File

Lai et al. supplementary material

Lai et al. supplementary material 4

Download Lai et al. supplementary material(File)
File 19.6 KB