Abstract
Rationale
Growing evidence supports the role of microbiota in regulating gut-brain interactions and, thus, contributing to the pathogenesis of depression and the antidepressant actions. Adipose-derived mesenchymal stem cells (ADSCs), as important members of the stem cell family, were demonstrated to alleviate depression behaviors. However, the role of gut microbiota in ADSCs alleviating depression in chronic social defeat stress (CSDS) model is unknown.
Objectives
To examine the effects of ADSCs on depression symptoms and detect the changes in the composition of gut microbiota.
Results
We found that ADSCs administration significantly ameliorated CSDS-induced depression behaviors, which was accompanied by alteration in the gut microbiota. The principal co-ordinates analysis (PCoA) results showed that there was a significant difference between the gut microbiota among the groups. Remarkably, receiver operating characteristic (ROC) curves revealed that order Micrococcales, order Rhizobiales and species Bacteroides acidifaciens are potentially important biomarkers for the antidepressant effects of ADSCs in CSDS model.
Conclusions
ADSCs are effective in treating depression behaviors in CSDS model, which might be partly due to the regulation of abnormal composition of gut microbiota. Thus, ADSCs offer a promising therapeutic strategy for treating depression in patients.
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References
Aizawa E, Tsuji H, Asahara T, Takahashi T, Teraishi T, Yoshida S, Ota M, Koga N, Hattori K, Kunugi H (2016) Possible association of Bifidobacterium and Lactobacillus in the gut microbiota of patients with major depressive disorder. J Affect Disord 202:254–257. https://doi.org/10.1016/j.jad.2016.05.038
Alballaa SR, Qadri SM, al-Furayh O, al-Qatary K (1992) Urinary tract infection due to Rahnella aquatilis in a renal transplant patient. J Clin Microbiol 30(11):2948–2950. https://doi.org/10.1128/jcm.30.11.2948-2950.1992
Assis RAB, Polloni LC, Patané JSL, Thakur S, Felestrino ÉB, Diaz-Caballero J, Digiampietri LA, Goulart LR, Almeida NF, Nascimento R, Dandekar AM, Zaini PA, Setubal JC, Guttman DS, Moreira LM (2017) Identification and analysis of seven effector protein families with different adaptive and evolutionary histories in plant-associated members of the Xanthomonadaceae. Sci Rep 7(1):16133. https://doi.org/10.1038/s41598-017-16325-1
Barandouzi ZA, Starkweather AR, Henderson WA, Gyamfi A, Cong XS (2020) Altered Composition of gut microbiota in depression: a systematic review. Front Psychiatry 11:541. https://doi.org/10.3389/fpsyt.2020.00541
Barcenilla A, Pryde SE, Martin JC, Duncan SH, Stewart CS, Henderson C, Flint HJ (2000) Phylogenetic relationships of butyrate-producing bacteria from the human gut. Appl Environ Microbiol 66(4):1654–1661. https://doi.org/10.1128/aem.66.4.1654-1661.2000
Bienenstock J, Kunze W, Forsythe P (2015) Microbiota and the gut-brain axis. Nutr Rev 73 Suppl 1:28–31. https://doi.org/10.1093/nutrit/nuv019
Bojović K, Ignjatović ÐI, Soković Bajić S, Vojnović Milutinović D, Tomić M, Golić N, Tolinački M (2020) Gut microbiota dysbiosis associated with altered production of short chain fatty acids in children with neurodevelopmental disorders. Front Cell Infect Microbiol 10:223. https://doi.org/10.3389/fcimb.2020.00223
Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM, Dinan TG, Bienenstock J, Cryan JF (2011) 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 108(38):16050–16055. https://doi.org/10.1073/pnas.1102999108
Burokas A, Arboleya S, Moloney RD, Peterson VL, Murphy K, Clarke G, Stanton C, Dinan TG, Cryan JF (2017) Targeting the microbiota-gut-brain axis: prebiotics have anxiolytic and antidepressant-like effects and reverse the impact of chronic stress in mice. Biol Psychiatry 82(7):472–487. https://doi.org/10.1016/j.biopsych.2016.12.031
Castrén E, Kojima M (2017) Brain-derived neurotrophic factor in mood disorders and antidepressant treatments. Neurobiol Dis 97(Pt B):119–126. https://doi.org/10.1016/j.nbd.2016.07.010
Cattaneo A, Cattane N, Galluzzi S, Provasi S, Lopizzo N, Festari C, Ferrari C, Guerra UP, Paghera B, Muscio C, Bianchetti A, Volta GD, Turla M, Cotelli MS, Gennuso M, Prelle A, Zanetti O, Lussignoli G, Mirabile D, Bellandi D, Gentile S, Belotti G, Villani D, Harach T, Bolmont T, Padovani A, Boccardi M, Frisoni GB (2017) Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly. Neurobiol Aging 49:60–68. https://doi.org/10.1016/j.neurobiolaging.2016.08.019
Chen X, Meng S, Li S, Zhang L, Wu L, Zhu H, Zhang Y (2021a) Role of 5-hydroxytryptamine and intestinal flora on depressive-like behavior induced by lead exposure in rats. Biomed Res Int 2021:5516604. https://doi.org/10.1155/2021/5516604
Chen Y, Meng P, Cheng S, Jia Y, Wen Y, Yang X, Yao Y, Pan C, Li C, Zhang H, Zhang J, Zhang Z, Zhang F (2021b) Assessing the effect of interaction between C-reactive protein and gut microbiome on the risks of anxiety and depression. Mol Brain 14(1):133. https://doi.org/10.1186/s13041-021-00843-1
Cheng S, Han B, Ding M, Wen Y, Ma M, Zhang L, Qi X, Cheng B, Li P, Kafle OP, Liang X, Liu L, Du Y, Zhao Y, Zhang F (2020) Identifying psychiatric disorder-associated gut microbiota using microbiota-related gene set enrichment analysis. Brief Bioinform 21(3):1016–1022. https://doi.org/10.1093/bib/bbz034
Cheung SG, Goldenthal AR, Uhlemann AC, Mann JJ, Miller JM, Sublette ME (2019) Systematic review of gut microbiota and major depression. Front Psychiatry 10:34. https://doi.org/10.3389/fpsyt.2019.00034
Choi JW, Kim GJ, Kim HJ, Nam JW, Kim J, Chin J, Park JH, Choi H, Park KD (2020) Identification and evaluation of a napyradiomycin as a potent Nrf2 activator: anti-oxidative and anti-inflammatory activities. Bioorg Chem 105:104434. https://doi.org/10.1016/j.bioorg.2020.104434
Ciocan D, Cassard AM, Becquemont L, Verstuyft C, Voican CS, El Asmar K, Colle R, David D, Trabado S, Feve B, Chanson P, Perlemuter G, Corruble E (2021) Blood microbiota and metabolomic signature of major depression before and after antidepressant treatment: a prospective case-control study. J Psychiatry Neurosci 46(3):E358-e368. https://doi.org/10.1503/jpn.200159
Constantin G, Marconi S, Rossi B, Angiari S, Calderan L, Anghileri E, Gini B, Bach SD, Martinello M, Bifari F, Galiè M, Turano E, Budui S, Sbarbati A, Krampera M, Bonetti B (2009) Adipose-derived mesenchymal stem cells ameliorate chronic experimental autoimmune encephalomyelitis. Stem Cells 27(10):2624–2635. https://doi.org/10.1002/stem.194
Cussotto S, Strain CR, Fouhy F, Strain RG, Peterson VL, Clarke G, Stanton C, Dinan TG, Cryan JF (2019) Differential effects of psychotropic drugs on microbiome composition and gastrointestinal function. Psychopharmacology 236(5):1671–1685. https://doi.org/10.1007/s00213-018-5006-5
Davis DJ, Hecht PM, Jasarevic E, Beversdorf DQ, Will MJ, Fritsche K, Gillespie CH (2017) Sex-specific effects of docosahexaenoic acid (DHA) on the microbiome and behavior of socially-isolated mice. Brain Behav Immun 59:38–48. https://doi.org/10.1016/j.bbi.2016.09.003
Deaver JA, Eum SY, Toborek M (2018) Circadian disruption changes gut microbiome taxa and functional gene composition. Front Microbiol 9:737. https://doi.org/10.3389/fmicb.2018.00737
Despres J, Forano E, Lepercq P, Comtet-Marre S, Jubelin G, Yeoman CJ, Miller ME, Fields CJ, Terrapon N, Le Bourvellec C, Renard CM, Henrissat B, White BA, Mosoni P (2016) Unraveling the pectinolytic function of Bacteroides xylanisolvens using a RNA-seq approach and mutagenesis. BMC Genomics 17:147. https://doi.org/10.1186/s12864-016-2472-1
Dinan TG, Cryan JF (2017) The Microbiome-gut-brain axis in health and disease. Gastroenterol Clin North Am 46(1):77–89. https://doi.org/10.1016/j.gtc.2016.09.007
Donohoe DR, Curry KP, Bultman SJ (2013) Microbial oncotarget: bacterial-produced butyrate, chemoprevention and Warburg effect. Oncotarget 4(2):182–183. https://doi.org/10.18632/oncotarget.915
Gaitán JI, Bronze MS (2010) Infection caused by Rahnella aquatilis. Am J Med Sci 339(6):577–579. https://doi.org/10.1097/maj.0b013e3181dd0cca
Gegunde S, Alfonso A, Alvariño R, Pérez-Fuentes N, Botana LM (2021) Anhydroexfoliamycin, a streptomyces secondary metabolite, mitigates microglia-driven inflammation. ACS Chem Neurosci 12(13):2336–2346. https://doi.org/10.1021/acschemneuro.1c00033
González MA, Gonzalez-Rey E, Rico L, Büscher D, Delgado M (2009) Adipose-derived mesenchymal stem cells alleviate experimental colitis by inhibiting inflammatory and autoimmune responses. Gastroenterology 136(3):978–989. https://doi.org/10.1053/j.gastro.2008.11.041
Gu L, Ren F, Fang X, Yuan L, Liu G, Wang S (2021) Exosomal microrna-181a derived from mesenchymal stem cells improves gut microbiota composition, barrier function, and inflammatory status in an experimental colitis model. Front Med 8:660614. https://doi.org/10.3389/fmed.2021.660614
Hall AB, Yassour M, Sauk J, Garner A, Jiang X, Arthur T, Lagoudas GK, Vatanen T, Fornelos N, Wilson R, Bertha M, Cohen M, Garber J, Khalili H, Gevers D, Ananthakrishnan AN, Kugathasan S, Lander ES, Blainey P, Vlamakis H, Xavier RJ, Huttenhower C (2017) A novel Ruminococcus gnavus clade enriched in inflammatory bowel disease patients. Genome Med 9(1):103. https://doi.org/10.1186/s13073-017-0490-5
Hehemann JH, Kelly AG, Pudlo NA, Martens EC, Boraston AB (2012) Bacteria of the human gut microbiome catabolize red seaweed glycans with carbohydrate-active enzyme updates from extrinsic microbes. Proc Natl Acad Sci U S A 109(48):19786–19791. https://doi.org/10.1073/pnas.1211002109
Huang N, Hua D, Zhan G, Li S, Zhu B, Jiang R, Yang L, Bi J, Xu H, Hashimoto K, Luo A, Yang C (2019) Role of Actinobacteria and Coriobacteriia in the antidepressant effects of ketamine in an inflammation model of depression. Pharmacol Biochem Behav 176:93–100. https://doi.org/10.1016/j.pbb.2018.12.001
Huang X, Fei GQ, Liu WJ, Ding J, Wang Y, Wang H, Ji JL, Wang X (2020) Adipose-derived mesenchymal stem cells protect against CMS-induced depression-like behaviors in mice via regulating the Nrf2/HO-1 and TLR4/NF-κB signaling pathways. Acta Pharmacol Sin 41(5):612–619. https://doi.org/10.1038/s41401-019-0317-6
Huang C, Wang Y, Wu Z, Xu J, Zhou L, Wang D, Yang L, Zhu B, Chen G, Liu C, Yang C (2021) miR-98-5p plays a critical role in depression and antidepressant effect of ketamine. Transl Psychiatry 11(1):454–454. https://doi.org/10.1038/s41398-021-01588-0
Huang R, Wang K, Hu J (2016) Effect of probiotics on depression: a systematic review and meta-analysis of randomized controlled trials. Nutrients 8(8). https://doi.org/10.3390/nu8080483
Ikarashi S, Tsuchiya A, Kawata Y, Kojima Y, Watanabe T, Takeuchi S, Igarashi K, Ideta-Otsuka M, Oki K, Takamura M, Terai S (2019) Effects of Human adipose tissue-derived and umbilical cord tissue-derived mesenchymal stem cells in a dextran sulfate sodium-induced mouse model. Biores Open Access 8(1):185–199. https://doi.org/10.1089/biores.2019.0022
Jiang H, Ling Z, Zhang Y, Mao H, Ma Z, Yin Y, Wang W, Tang W, Tan Z, Shi J, Li L, Ruan B (2015) Altered fecal microbiota composition in patients with major depressive disorder. Brain Behav Immun 48:186–194. https://doi.org/10.1016/j.bbi.2015.03.016
Jiang X, Lu N, Zhao H, Yuan H, Xia D, Lei H (2020) The Microbiome-metabolome response in the colon of piglets under the status of weaning stress. Front Microbiol 11:2055. https://doi.org/10.3389/fmicb.2020.02055
Kang HJ, Kim SY, Bae KY, Kim SW, Shin IS, Yoon JS, Kim JM (2015) Comorbidity of depression with physical disorders: research and clinical implications. Chonnam Med J 51(1):8–18. https://doi.org/10.4068/cmj.2015.51.1.8
Kim HJ, Leeds P, Chuang DM (2009) The HDAC inhibitor, sodium butyrate, stimulates neurogenesis in the ischemic brain. J Neurochem 110(4):1226–1240. https://doi.org/10.1111/j.1471-4159.2009.06212.x
Kuang Y, Zheng X, Zhang L, Ai X, Venkataramani V, Kilic E, Hermann DM, Majid A, Bähr M, Doeppner TR (2020) Adipose-derived mesenchymal stem cells reduce autophagy in stroke mice by extracellular vesicle transfer of miR-25. J Extracell Vesicles 10(1):e12024. https://doi.org/10.1002/jev2.12024
Lee SK, Lee DR, Choi BK, Palaniyandi SA, Yang SH, Suh JW (2015) Glutathione S-transferase pi (GST-pi) inhibition and anti-inflammation activity of the ethyl acetate extract of Streptomyces sp. strain MJM 8637. Saudi J Biol Sci 22(6):744–751. https://doi.org/10.1016/j.sjbs.2015.04.003
Lee SY, Kwon B, Lee K, Son YH, Chung SG (2017) Therapeutic mechanisms of human adipose-derived mesenchymal stem cells in a rat tendon injury model. Am J Sports Med 45(6):1429–1439. https://doi.org/10.1177/0363546517689874
Li C, Gao M, Zhang W, Chen C, Zhou F, Hu Z, Zeng C (2016a) Zonulin regulates intestinal permeability and facilitates enteric bacteria permeation in coronary artery disease. Sci Rep 6:29142. https://doi.org/10.1038/srep29142
Li D, Wang P, Wang P, Hu X, Chen F (2016b) The gut microbiota: a treasure for human health. Biotechnol Adv 34(7):1210–1224. https://doi.org/10.1016/j.biotechadv.2016.08.003
Lu Q, Lai J, Lu H, Ng C, Huang T, Zhang H, Ding K, Wang Z, Jiang J, Hu J, Lu J, Lu S, Mou T, Wang D, Du Y, Xi C, Lyu H, Chen J, Xu Y, Liu Z, Hu S (2019) Gut microbiota in bipolar depression and its relationship to brain function: an advanced exploration. Front Psychiatry 10:784. https://doi.org/10.3389/fpsyt.2019.00784
Lukić I, Getselter D, Ziv O, Oron O, Reuveni E, Koren O, Elliott E (2019) Antidepressants affect gut microbiota and Ruminococcus flavefaciens is able to abolish their effects on depressive-like behavior. Transl Psychiatry 9(1):133. https://doi.org/10.1038/s41398-019-0466-x
Ma Q, Xing C, Long W, Wang HY, Liu Q, Wang RF (2019) Impact of microbiota on central nervous system and neurological diseases: the gut-brain axis. J Neuroinflamm 16(1):53. https://doi.org/10.1186/s12974-019-1434-3
Macfarlane GT, Macfarlane S (2011) Fermentation in the human large intestine: its physiologic consequences and the potential contribution of prebiotics. J Clin Gastroenterol 45 Suppl:S120-127. https://doi.org/10.1097/MCG.0b013e31822fecfe
Mahan KM, Zheng H, Fida TT, Parry RJ, Graham DE, Spain JC (2017) Iron-dependent enzyme catalyzes the initial step in biodegradation of N-nitroglycine by Variovorax sp. strain JS1663. Appl Environ Microbiol 83(15). https://doi.org/10.1128/aem.00457-17
Mahmoud ME, Rehan IF, El-Dawy Ahmed K, Abdelrahman A, Mohammadi S, Abou-Elnaga AF, Youssef M, Diab HM, Salman D, Elnagar A, Mohammed HH, Shanab O, Ibrahim RM, Ahmed EKH, Hesham AE, Gupta A (2019) Identification of serum N-glycoproteins as a biological correlate underlying chronic stress response in mice. Mol Biol Rep 46(3):2733–2748. https://doi.org/10.1007/s11033-019-04717-7
Mao YX, Xu JF, Seeley EJ, Tang XD, Xu LL, Zhu YG, Song YL, Qu JM (2015) Adipose tissue-derived mesenchymal stem cells attenuate pulmonary infection caused by Pseudomonas aeruginosa via inhibiting overproduction of prostaglandin E2. Stem Cells 33(7):2331–2342. https://doi.org/10.1002/stem.1996
Mathews DC, Henter ID, Zarate CA (2012) Targeting the glutamatergic system to treat major depressive disorder: rationale and progress to date. Drugs 72(10):1313–1333. https://doi.org/10.2165/11633130-000000000-00000
Mekonen T, Chan GCK, Connor JP, Hides L, Leung J (2021) Estimating the global treatment rates for depression: a systematic review and meta-analysis. J Affect Disord 295:1234–1242. https://doi.org/10.1016/j.jad.2021.09.038
Naik S, Larsen SB, Cowley CJ, Fuchs E (2018) Two to tango: dialog between immunity and stem cells in health and disease. Cell 175(4):908–920. https://doi.org/10.1016/j.cell.2018.08.071
Park HJ, Oh SH, Kim HN, Jung YJ, Lee PH (2016) Mesenchymal stem cells enhance α-synuclein clearance via M2 microglia polarization in experimental and human parkinsonian disorder. Acta Neuropathol 132(5):685–701. https://doi.org/10.1007/s00401-016-1605-6
Pryde SE, Duncan SH, Hold GL, Stewart CS, Flint HJ (2002) The microbiology of butyrate formation in the human colon. FEMS Microbiol Lett 217(2):133–139. https://doi.org/10.1111/j.1574-6968.2002.tb11467.x
Rajilić-Stojanović M, Jonkers DM, Salonen A, Hanevik K, Raes J, Jalanka J, de Vos WM, Manichanh C, Golic N, Enck P, Philippou E, Iraqi FA, Clarke G, Spiller RC, Penders J (2015) Intestinal microbiota and diet in IBS: causes, consequences, or epiphenomena? Am J Gastroenterol 110(2):278–287. https://doi.org/10.1038/ajg.2014.427
Shwartz A, Betzer O, Kronfeld N, Kazimirsky G, Cazacu S, Finniss S, Lee HK, Motiei M, Dagan SY, Popovtzer R, Brodie C, Yadid G (2017) Therapeutic effect of astroglia-like mesenchymal stem cells expressing glutamate transporter in a genetic rat model of depression. Theranostics 7(10):2690–2703. https://doi.org/10.7150/thno.18914
Spaeth E, Klopp A, Dembinski J, Andreeff M, Marini F (2008) Inflammation and tumor microenvironments: defining the migratory itinerary of mesenchymal stem cells. Gene Ther 15(10):730–738. https://doi.org/10.1038/gt.2008.39
Sun L, Ma L, Zhang H, Cao Y, Wang C, Hou N, Huang N, von Deneen KM, Zhao C, Shi Y, Pan Y, Wang M, Ji G, Nie Y (2019) Fto deficiency reduces anxiety- and depression-like behaviors in mice via alterations in gut microbiota. Theranostics 9(3):721–733. https://doi.org/10.7150/thno.31562
Sun J, Ding X, Liu S, Duan X, Liang H, Sun T (2020) Adipose-derived mesenchymal stem cells attenuate acute lung injury and improve the gut microbiota in septic rats. Stem Cell Res Ther 11(1):384. https://doi.org/10.1186/s13287-020-01902-5
Tfilin M, Sudai E, Merenlender A, Gispan I, Yadid G, Turgeman G (2010) Mesenchymal stem cells increase hippocampal neurogenesis and counteract depressive-like behavior. Mol Psychiatry 15(12):1164–1175. https://doi.org/10.1038/mp.2009.110
Thomas JC, Helgason T, Sinclair CJ, Moir JWB (2017) Isolation and characterization of metaldehyde-degrading bacteria from domestic soils. Microb Biotechnol 10(6):1824–1829. https://doi.org/10.1111/1751-7915.12719
Venkataraman A, Sieber JR, Schmidt AW, Waldron C, Theis KR, Schmidt TM (2016) Variable responses of human microbiomes to dietary supplementation with resistant starch. Microbiome 4(1):33. https://doi.org/10.1186/s40168-016-0178-x
Wang L, Christophersen CT, Sorich MJ, Gerber JP, Angley MT, Conlon MA (2013) Increased abundance of Sutterella spp. and Ruminococcus torques in feces of children with autism spectrum disorder. Mol Autism 4(1):42. https://doi.org/10.1186/2040-2392-4-42
Wang S, Qu Y, Chang L, Pu Y, Zhang K, Hashimoto K (2020) Antibiotic-induced microbiome depletion is associated with resilience in mice after chronic social defeat stress. J Affect Disord 260:448–457. https://doi.org/10.1016/j.jad.2019.09.064
Wang Y, Jiang R, Wu Z, Zhou L, Xu J, Huang C, Yang L, Zhu B, Yan E, Liu C, Yang C (2021) Gut microbiota is involved in the antidepressant-like effect of (S)-norketamine in an inflammation model of depression. Pharmacol Biochem Behav 207:173226. https://doi.org/10.1016/j.pbb.2021.173226
WHO (2021) Depression. https://www.who.int/en/news-room/fact-sheets/detail/depression. Accessed 13 Sept 2021
Woo HL, DeAngelis KM, Teshima H, Davenport K, Daligault H, Erkkila T, Goodwin L, Gu W, Lo CC, Munk C, Scholz M, Xu Y, Chain P, Bruce D, Detter C, Tapia R, Han C, Simmons BA, Hazen TC (2017) High-quality draft genome sequences of four lignocellulose-degrading bacteria isolated from puerto rican forest soil: Gordonia sp., Paenibacillus sp., Variovorax sp., and Vogesella sp. Genome Announc 5(18). https://doi.org/10.1128/genomeA.00300-17
Xu M, Jiang Z, Huang W, Yin J, Ou S, Jiang Y, Meng L, Cao S, Yu A, Cao J, Shen Y (2018) Altered gut microbiota composition in subjects infected with Clonorchis sinensis. Front Microbiol 9:2292. https://doi.org/10.3389/fmicb.2018.02292
Xue J, Li X, Liu P, Li K, Sha L, Yang X, Zhu L, Wang Z, Dong Y, Zhang L, Lei H, Zhang X, Dong X, Wang H (2019) Inulin and metformin ameliorate polycystic ovary syndrome via anti-inflammation and modulating gut microbiota in mice. Endocr J 66(10):859–870. https://doi.org/10.1507/endocrj.EJ18-0567
Yang C, Shirayama Y, Zhang J, Ren Q, Yao W, Ma M, Dong C, Hashimoto K (2015) R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects. Transl Psychiatry 5:e632. https://doi.org/10.1038/tp.2015.136
Yang C, Fujita Y, Ren Q, Ma M, Dong C, Hashimoto K (2017) Bifidobacterium in the gut microbiota confer resilience to chronic social defeat stress in mice. Sci Rep 7:45942. https://doi.org/10.1038/srep45942
Yang C, Fang X, Zhan G, Huang N, Li S, Bi J, Jiang R, Yang L, Miao L, Zhu B, Luo A, Hashimoto K (2019) Key role of gut microbiota in anhedonia-like phenotype in rodents with neuropathic pain. Transl Psychiatry 9(1):57. https://doi.org/10.1038/s41398-019-0379-8
Yang Q, Luo L, Sun T, Yang L, Cheng LF, Wang Y, Liu QQ, Liu A, Liu HY, Zhao MG, Wu SX, Feng B (2020a) Chronic minocycline treatment exerts antidepressant effect, inhibits neuroinflammation, and modulates gut microbiota in mice. Psychopharmacology 237(10):3201–3213. https://doi.org/10.1007/s00213-020-05604-x
Yang Z, Xia Q, Lu D, Yue H, Zhang J, Li Y, Zhang B, Li X, Cao M (2020b) Human mesenchymal stem cells treatment improved hepatic lesions and reversed gut microbiome disorder in non-alcoholic steatohepatitis. Aging 12(21):21660–21673. https://doi.org/10.18632/aging.103962
Zhan G, Yang N, Li S, Huang N, Fang X, Zhang J, Zhu B, Yang L, Yang C, Luo A (2018) Abnormal gut microbiota composition contributes to cognitive dysfunction in SAMP8 mice. Aging 10(6):1257–1267. https://doi.org/10.18632/aging.101464
Zhao RH, Zheng PY, Liu SM, Tang YC, Li EY, Sun ZY, Jiang MM (2019) Correlation between gut microbiota and behavior symptoms in children with autism spectrum disorder. Zhongguo Dang Dai Er Ke Za Zhi 21(7):663–669. https://doi.org/10.7499/j.issn.1008-8830.2019.07.009
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, Xie P (2016) Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host’s metabolism. Mol Psychiatry 21(6):786–796. https://doi.org/10.1038/mp.2016.44
Zinkernagel MS, Zysset-Burri DC, Keller I, Berger LE, Leichtle AB, Largiadèr CR, Fiedler GM, Wolf S (2017) Association of the intestinal microbiome with the development of neovascular age-related macular degeneration. Sci Rep 7:40826. https://doi.org/10.1038/srep40826
Zuk PA (2010) The adipose-derived stem cell: looking back and looking ahead. Mol Biol Cell 21(11):1783–1787. https://doi.org/10.1091/mbc.e09-07-0589
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This study was supported by grants from the National Natural Science Foundation of China (no. 81971624, 81901759).
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Jiang, R., Wang, Y., Liu, J. et al. Gut microbiota is involved in the antidepressant effects of adipose-derived mesenchymal stem cells in chronic social defeat stress mouse model. Psychopharmacology 239, 533–549 (2022). https://doi.org/10.1007/s00213-021-06037-w
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DOI: https://doi.org/10.1007/s00213-021-06037-w