{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T20:41:29Z","timestamp":1792528889329,"version":"4.5.0"},"reference-count":42,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T00:00:00Z","timestamp":1647216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82173500"],"award-info":[{"award-number":["82173500"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Recent studies have reported a strong association between gestational diabetes mellitus (GDM) and postpartum depression (PPD), but little is known about the underlying physiological mechanism. In this study, a GDM rat model was used to evaluate the direct effect of GDM on PPD and to explore the mechanism. After parturition, the GDM dams were divided into two groups: blood glucose not recovered group (GH group) and blood glucose recovered group (GL group). Fasting plasma glucose (FPG), cortisol (COR) and serotonin (5-hydroxytryptamine, 5-HT) metabolism were continuously monitored during the lactation period, until postnatal day 21. PPD was evaluated by behavioral tests. At the endpoint, the expression of the key enzymes of Trp metabolic pathway in colon and brain tissues was analyzed by immunohistochemistry and western blot. The microbe composition of colonic contents was determined by 16S rDNA gene sequencing. The results showed that GDM induced postpartum depression-like behavior in rats. The HPA axis hormone did not show the typical stress state of depression, but the level of 5-HT decreased significantly in serum, prefrontal cortex and hippocampus, and the Kyn\/Trp ratio increased significantly in serum and prefrontal cortex, implying the switch of the tryptophan (Trp) metabolism from the 5-HT pathway to the kynurenine (Kyn) pathway. The expression of Indoleamine 2,3-dioxygenase (IDO), a key rate-limiting enzyme in Kyn metabolism, was up-regulated in the colon and brain, which was an important reason for this switch. This switch was accelerated by a decrease in the expression of tryptophan hydroxylase (TPH), a key enzyme of the 5-HT production pathway, in the colon. GDM dams displayed significant changes in gut microbiome profiles, which were correlated with depression. The ratio of Firmicutes to Bacteroidetes decreased. Lactobacillus and Bacteroides were negatively correlated with 5-HT level and positively correlated with Kyn level, whereas Clostridium XlVa and Ruminococcus were positively correlated with 5-HT level. These results suggest that GDM disrupts both the Trp pathway and the composition of the gut microbiota, which provide a putative physiological basis for PPD.<\/jats:p>","DOI":"10.3390\/nu14061229","type":"journal-article","created":{"date-parts":[[2022,3,15]],"date-time":"2022-03-15T02:56:20Z","timestamp":1647312980000},"page":"1229","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Effect of Gestational Diabetes on Postpartum Depression-like Behavior in Rats and Its Mechanism"],"prefix":"10.3390","volume":"14","author":[{"given":"Runlong","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Peking University, No. 38 Xueyuan Road, Beijing 100083, China"},{"name":"PKUHSC\u2014China Feihe Joint Research Institute of Nutrition and Healthy Lifespan Development, No. 38 Xueyuan Road, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yalin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Peking University, No. 38 Xueyuan Road, Beijing 100083, China"},{"name":"PKUHSC\u2014China Feihe Joint Research Institute of Nutrition and Healthy Lifespan Development, No. 38 Xueyuan Road, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanxu","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Peking University, No. 38 Xueyuan Road, Beijing 100083, China"},{"name":"PKUHSC\u2014China Feihe Joint Research Institute of Nutrition and Healthy Lifespan Development, No. 38 Xueyuan Road, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanyun","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Peking University, No. 38 Xueyuan Road, Beijing 100083, China"},{"name":"PKUHSC\u2014China Feihe Joint Research Institute of Nutrition and Healthy Lifespan Development, No. 38 Xueyuan Road, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Lyu","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Peking University, No. 38 Xueyuan Road, Beijing 100083, China"},{"name":"PKUHSC\u2014China Feihe Joint Research Institute of Nutrition and Healthy Lifespan Development, No. 38 Xueyuan Road, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhang","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Peking University, No. 38 Xueyuan Road, Beijing 100083, China"},{"name":"PKUHSC\u2014China Feihe Joint Research Institute of Nutrition and Healthy Lifespan Development, No. 38 Xueyuan Road, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Peking University, No. 38 Xueyuan Road, Beijing 100083, China"},{"name":"PKUHSC\u2014China Feihe Joint Research Institute of Nutrition and Healthy Lifespan Development, No. 38 Xueyuan Road, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5791-4629","authenticated-orcid":false,"given":"Yajun","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Peking University, No. 38 Xueyuan Road, Beijing 100083, China"},{"name":"PKUHSC\u2014China Feihe Joint Research Institute of Nutrition and Healthy Lifespan Development, No. 38 Xueyuan Road, Beijing 100083, China"},{"name":"Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Peking University, No. 38 Xueyuan Road, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1001\/jamapsychiatry.2013.87","article-title":"Onset timing, thoughts of self-harm, and diagnoses in postpartum women with screen-positive depression findings","volume":"70","author":"Wisner","year":"2013","journal-title":"JAMA Psychiatry"},{"key":"ref_2","first-page":"9","article-title":"A Review of Postpartum Depression","volume":"1","year":"1999","journal-title":"Prim. Care Companion J. Clin. Psychiatry"},{"key":"ref_3","first-page":"926","article-title":"Postpartum major depression","volume":"82","author":"Hirst","year":"2010","journal-title":"Am. Fam. Phys."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.psyneuen.2017.12.003","article-title":"Inability to suppress the stress-induced activation of the HPA axis during the peripartum period engenders deficits in postpartum behaviors in mice","volume":"90","author":"Hooper","year":"2018","journal-title":"Psychoneuroendocrinology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/j.pnpbp.2009.09.006","article-title":"Depression during pregnancy and postpartum: Contribution of stress and ovarian hormones","volume":"34","author":"Brummelte","year":"2010","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.tins.2008.06.006","article-title":"The HPA axis in major depression: Classical theories and new developments","volume":"31","author":"Pariante","year":"2008","journal-title":"Trends Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"949","DOI":"10.2174\/1381612822666151214104826","article-title":"Depression, Serotonin and Tryptophan","volume":"22","author":"Carmassi","year":"2016","journal-title":"Curr. Pharm. Des."},{"key":"ref_8","first-page":"274","article-title":"Plasma concentrations of neurotransmitters and postpartum depression","volume":"43","author":"Xie","year":"2018","journal-title":"Zhong Nan Da Xue Xue Bao Yi Xue Ban"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/s41564-018-0337-x","article-title":"The neuroactive potential of the human gut microbiota in quality of life and depression","volume":"4","author":"Falony","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.bbi.2015.03.016","article-title":"Altered fecal microbiota composition in patients with major depressive disorder","volume":"48","author":"Jiang","year":"2015","journal-title":"Brain Behav. Immun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1111\/jog.12471","article-title":"Predictors and incidence of post-partum depression: A longitudinal cohort study","volume":"40","author":"Abdollahi","year":"2014","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1002\/da.22597","article-title":"The risk factors for postpartum depression: A population-based study","volume":"34","author":"Silverman","year":"2017","journal-title":"Depress. Anxiety"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.jad.2019.05.001","article-title":"Gestational diabetes and risk of postpartum depressive symptoms: A meta-analysis of cohort studies","volume":"253","author":"Arafa","year":"2019","journal-title":"J. Affect. Disord."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"90","DOI":"10.3109\/0167482X.2013.786036","article-title":"A study of postpartum depression and maternal risk factors in Qatar","volume":"34","author":"Burgut","year":"2013","journal-title":"J. Psychosom. Obstet. Gynaecol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"102353","DOI":"10.1016\/j.ajp.2020.102353","article-title":"Risk factors for postpartum depression: An evidence-based systematic review of systematic reviews and meta-analyses","volume":"53","author":"Zhao","year":"2020","journal-title":"Asian J. Psychiatry"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"25","DOI":"10.2174\/1871530319666190626143832","article-title":"Future Perspective of Diabetic Animal Models","volume":"20","author":"Pandey","year":"2020","journal-title":"Endocr. Metab. Immune Disord. Drug Targets"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"473575","DOI":"10.1155\/2013\/473575","article-title":"Mild diabetes models and their maternal-fetal repercussions","volume":"2013","author":"Damasceno","year":"2013","journal-title":"J. Diabetes Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1515\/intox-2017-0006","article-title":"Animal tests for anxiety-like and depression-like behavior in rats","volume":"10","author":"Belovicova","year":"2017","journal-title":"Interdiscip. Toxicol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/978-1-4939-8994-2_4","article-title":"The Elevated Plus Maze Test for Measuring Anxiety-Like Behavior in Rodents","volume":"1916","author":"Kraeuter","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Yankelevitch-Yahav, R., Franko, M., Huly, A., and Doron, R. (2015). The forced swim test as a model of depressive-like behavior. J. Vis. Exp., e52587.","DOI":"10.3791\/52587"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.physbeh.2009.10.011","article-title":"Anhedonia in postpartum rats","volume":"99","author":"Navarre","year":"2010","journal-title":"Physiol. Behav."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.eururo.2019.06.030","article-title":"Prostate-specific Membrane Antigen Heterogeneity and DNA Repair Defects in Prostate Cancer","volume":"76","author":"Paschalis","year":"2019","journal-title":"Eur. Urol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.jad.2014.09.022","article-title":"Breastfeeding and depression: A systematic review of the literature","volume":"171","author":"Dias","year":"2015","journal-title":"J. Affect. Disord."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1017\/S0033291798006680","article-title":"Mood and neuropsychological function in depression: The role of corticosteroids and serotonin","volume":"28","author":"Ferrier","year":"1998","journal-title":"Psychol. Med."},{"key":"ref_25","first-page":"103","article-title":"Chronic unpredictable mild stress paradigm in male Wistar rats: Effect on anxiety- and depressive-like behavior","volume":"37","author":"Koprdova","year":"2016","journal-title":"Neuro Endocrinol. Lett."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.yhbeh.2010.07.012","article-title":"Chronic corticosterone during pregnancy and postpartum affects maternal care, cell proliferation and depressive-like behavior in the dam","volume":"58","author":"Brummelte","year":"2010","journal-title":"Horm. Behav."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1038\/mp.2012.128","article-title":"Lack of brain serotonin affects postnatal development and serotonergic neuronal circuitry formation","volume":"18","author":"Migliarini","year":"2013","journal-title":"Mol. Psychiatry"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1002\/ijgo.13351","article-title":"Predictive value of serum CRH\/5-HT ratio for postpartum depression","volume":"151","author":"Cao","year":"2020","journal-title":"Int. J. Gynaecol. Obstet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1016\/j.pnpbp.2008.04.010","article-title":"Sequential serotonin and noradrenalin associated processes involved in postpartum blues","volume":"32","author":"Doornbos","year":"2008","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1178646919852996","DOI":"10.1177\/1178646919852996","article-title":"Microorganisms, Tryptophan Metabolism, and Kynurenine Pathway: A Complex Interconnected Loop Influencing Human Health Status","volume":"12","author":"Dehhaghi","year":"2019","journal-title":"Int. J. Tryptophan Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1080\/15622975.2018.1468031","article-title":"Reduced peripheral availability of tryptophan and increased activation of the kynurenine pathway and cortisol correlate with major depression and suicide","volume":"20","author":"Messaoud","year":"2019","journal-title":"World J. Biol. Psychiatry"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Laugeray, A., Launay, J.M., Callebert, J., Mutlu, O., Guillemin, G.J., Belzung, C., and Barone, P.R. (2016). Chronic Treatment with the IDO1 Inhibitor 1-Methyl-D-Tryptophan Minimizes the Behavioural and Biochemical Abnormalities Induced by Unpredictable Chronic Mild Stress in Mice\u2014Comparison with Fluoxetine. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0164337"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Tao, X., Yan, M., Wang, L., Zhou, Y., Wang, Z., Xia, T., Liu, X., Pan, R., and Chang, Q. (2020). Homeostasis Imbalance of Microglia and Astrocytes Leads to Alteration in the Metabolites of the Kynurenine Pathway in LPS-Induced Depressive-Like Mice. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041460"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/nature24628","article-title":"Salt-responsive gut commensal modulates T(H)17 axis and disease","volume":"551","author":"Wilck","year":"2017","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/19490976.2020.1869501","article-title":"Involvement of the microbiota-gut-brain axis in chronic restraint stress: Disturbances of the kynurenine metabolic pathway in both the gut and brain","volume":"13","author":"Deng","year":"2021","journal-title":"Gut Microbes"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3045","DOI":"10.1128\/IAI.00193-08","article-title":"Deficiency of indoleamine 2,3-dioxygenase enhances commensal-induced antibody responses and protects against Citrobacter rodentium-induced colitis","volume":"76","author":"Harrington","year":"2008","journal-title":"Infect. Immun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"547","DOI":"10.3389\/fnins.2018.00547","article-title":"Involvement of Innate and Adaptive Immune Systems Alterations in the Pathophysiology and Treatment of Depression","volume":"12","author":"Lowell","year":"2018","journal-title":"Front. Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Park, H.J., Kim, S.A., Kang, W.S., and Kim, J.W. (2021). Early-Life Stress Modulates Gut Microbiota and Peripheral and Central Inflammation in a Sex-Dependent Manner. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041899"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.ebiom.2017.09.020","article-title":"Microbiota-related Changes in Bile Acid & Tryptophan Metabolism are Associated with Gastrointestinal Dysfunction in a Mouse Model of Autism","volume":"24","author":"Golubeva","year":"2017","journal-title":"EBioMedicine"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1038\/ismej.2015.127","article-title":"Microorganisms linked to inflammatory bowel disease-associated dysbiosis differentially impact host physiology in gnotobiotic mice","volume":"10","author":"Hoffmann","year":"2016","journal-title":"ISME J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1016\/0016-5085(94)90526-6","article-title":"Microflora modulates endocrine cells in the gastrointestinal mucosa of the rat","volume":"107","author":"Uribe","year":"1994","journal-title":"Gastroenterology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/s11427-014-4615-4","article-title":"Ingestion of Lactobacillus strain reduces anxiety and improves cognitive function in the hyperammonemia rat","volume":"57","author":"Luo","year":"2014","journal-title":"Sci. China Life Sci."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/6\/1229\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:36:28Z","timestamp":1760135788000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/6\/1229"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,14]]},"references-count":42,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["nu14061229"],"URL":"https:\/\/doi.org\/10.3390\/nu14061229","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,14]]}}}