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image of Bridging Mind and Gut: The Molecular Mechanisms of microRNA, Microbiota, and Cytokine Interactions in Depression

Abstract

Depression is a complex psychiatric disorder that arises from various underlying biological mechanisms. In this review, the role of microRNAs (miRNAs) in modulating gut microbiota-cytokine communication and their potential to unravel the pathophysiology of depression and develop novel therapeutic strategies are discussed. MiRNAs are small non-coding RNA molecules that have emerged as key regulators in the bidirectional signaling of the gut-brain axis by modulating gene expression and fine-tuning an intricate dialogue between the microbiota, immune system, and central nervous system. Results show how gut microbiota can shape miRNA expression in brain regions involved in mood regulation; conversely, evidence is accumulating, elucidating how miRNA perturbations can shape microbial ecology. Gut bacteria-derived short-chain fatty acids (SCFAs) fuel this nexus by exerting effects on neurogenesis, neurotransmitter synthesis, neuroinflammation, affective behavior alterations, and depressive-like phenotypes. Pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β are also known to be associated with depressive symptoms related to altered expression patterns of specific miRNAs across these disorders. This review exposes the novel potential biomarkers and therapeutic targets/strategies to develop innovative methods in the diagnosis and treatment of depression by exploring bidirectional relations among miRNAs, gut microbiota, and cytokines. The knowledge of these molecular networks and pathways has provided the opportunity for designing new-generation therapeutics such as phytobiotics, probiotics, psychobiotics, diet therapies, and nanomedicine based on miRNAs from a future perspective, which will revolutionize the management of mental disorders.

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2025-06-27
2025-09-13

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References

  1. Haas-Neill S. Forsythe P. A budding relationship: Bacterial extracellular vesicles in the microbiota-gut-brain axis. Int. J. Mol. Sci. 2020 21 23 8899 10.3390/ijms21238899 33255332
    [Google Scholar]
  2. Ding R. Su D. Zhao Q. The role of microRNAs in depression. Front. Pharmacol. 2023 14 1129186 10.3389/fphar.2023.1129186 37063278
    [Google Scholar]
  3. Rupaimoole R. Slack F.J. MicroRNA therapeutics: Towards a new era for the management of cancer and other diseases. Nat. Rev. Drug Discov. 2017 16 3 203 222 10.1038/nrd.2016.246 28209991
    [Google Scholar]
  4. Li M. Chen W.D. Wang Y.D. The roles of the gut microbiota–miRNA interaction in the host pathophysiology. Mol. Med. 2020 26 1 101 10.1186/s10020‑020‑00234‑7 33160314
    [Google Scholar]
  5. Barandouzi Z.A. Starkweather A.R. Henderson W.A. Gyamfi A. Cong X.S. Altered composition of gut microbiota in depression: A systematic review. Front. Psychiatry 2020 11 541 10.3389/fpsyt.2020.00541 32587537
    [Google Scholar]
  6. Li Q. Zhang J. Gao Z. Zhang Y. Gu J. Gut microbiota-induced microRNA-206-3p increases anxiety-like behaviors by inhibiting expression of Cited2 and STK39. Microb. Pathog. 2023 176 106008 10.1016/j.micpath.2023.106008 36736544
    [Google Scholar]
  7. Chen H.M. Chung Y.C.E. Chen H.C. Liu Y.W. Chen I.M. Lu M.L. Exploration of the relationship between gut microbiota and fecal microRNAs in patients with major depressive disorder. Sci. Rep. 2022 12 1 20977 10.1038/s41598‑022‑24773‑7 36470908
    [Google Scholar]
  8. Xiong R.G. Li J. Cheng J. Zhou D.D. Wu S.X. Huang S.Y. The role of gut microbiota in anxiety, depression, and other mental disorders as well as the protective effects of dietary components. Nutrients 2023 15 14 3258 10.3390/nu15143258 37513676
    [Google Scholar]
  9. Rathour D. Shah S. Khan S. Role of gut microbiota in depression: Understanding molecular pathways, recent research, and future direction. Behav. Brain Res. 2023 436 114081 10.1016/j.bbr.2022.114081 36037843
    [Google Scholar]
  10. Liu Y. Wang H. Gui S. Zeng B. Pu J. Zheng P. Proteomics analysis of the gut–brain axis in a gut microbiota-dysbiosis model of depression. Transl. Psychiatry 2021 11 1 568 10.1038/s41398‑021‑01689‑w 34744165
    [Google Scholar]
  11. Liu P. Liu Z. Wang J. Wang J. Gao M. Zhang Y. Immunoregulatory role of the gut microbiota in inflammatory depression. Nat. Commun. 2024 15 1 3003 10.1038/s41467‑024‑47273‑w 38589368
    [Google Scholar]
  12. Liang S. Wu X. Hu X. Wang T. Jin F. Recognizing Depression from the Microbiota–Gut–Brain Axis. Int. J. Mol. Sci. 2018 19 6 1592 10.3390/ijms19061592 29843470
    [Google Scholar]
  13. Maes M. Kubera M. Leunis J.C. Berk M. Increased IgA and IgM responses against gut commensals in chronic depression: Further evidence for increased bacterial translocation or leaky gut. J. Affect. Disord. 2012 141 1 55 62 10.1016/j.jad.2012.02.023 22410503
    [Google Scholar]
  14. Moloney G.M. Dinan T.G. Clarke G. Cryan J.F. Microbial regulation of microRNA expression in the brain–gut axis. Curr. Opin. Pharmacol. 2019 48 120 126 10.1016/j.coph.2019.08.005 31590111
    [Google Scholar]
  15. Valdes A.M. Walter J. Segal E. Spector T.D. Role of the gut microbiota in nutrition and health. BMJ 2018 361 k2179 10.1136/bmj.k2179 29899036
    [Google Scholar]
  16. Satterthwaite T.D. Vandekar S.N. Wolf D.H. Connectome-wide network analysis of youth with Psychosis-Spectrum symptoms. Mol. Psychiatry 2015 20 12 1508 1515 10.1038/mp.2015.66 26033240
    [Google Scholar]
  17. Hern Ã. ¡ndez-Prieto MA, Semeniuk TA, Futschik ME. Toward a systems-level understanding of gene regulatory, protein interaction, and metabolic networks in cyanobacteria. Front. Genet. 2014 5 191
    [Google Scholar]
  18. Thompson J.M. Yakhnitsa V. Ji G. Neugebauer V. Small conductance calcium activated potassium (SK) channel dependent and independent effects of riluzole on neuropathic pain-related amygdala activity and behaviors in rats. Neuropharmacology 2018 138 219 231 10.1016/j.neuropharm.2018.06.015 29908238
    [Google Scholar]
  19. Cathomas F. Murrough J.W. Nestler E.J. Han M.H. Russo S.J. Neurobiology of resilience: Interface between mind and body. Biol. Psychiatry 2019 86 6 410 420 10.1016/j.biopsych.2019.04.011 31178098
    [Google Scholar]
  20. Kelly J.R. Kennedy P.J. Cryan J.F. Dinan T.G. Clarke G. Hyland N.P. Breaking down the barriers: The gut microbiome, intestinal permeability and stress-related psychiatric disorders. Front. Cell. Neurosci. 2015 9 392 10.3389/fncel.2015.00392 26528128
    [Google Scholar]
  21. Gubert C. Hannan A.J. Exercise mimetics: Harnessing the therapeutic effects of physical activity. Nat. Rev. Drug Discov. 2021 20 11 862 879 10.1038/s41573‑021‑00217‑1 34103713
    [Google Scholar]
  22. Casado-Bedmar M. Viennois E. MicroRNA and gut microbiota: Tiny but mighty—Novel insights into their cross-talk in inflammatory bowel disease pathogenesis and therapeutics. J. Crohn’s Colitis 2022 16 6 992 1005 10.1093/ecco‑jcc/jjab223 34918052
    [Google Scholar]
  23. Luczynski P. McVey Neufeld K.A. Oriach C.S. Clarke G. Dinan T.G. Cryan J.F. Growing up in a bubble: Using germ-free animals to assess the influence of the gut microbiota on brain and behavior. Int. J. Neuropsychopharmacol. 2016 19 8 pyw020 10.1093/ijnp/pyw020 26912607
    [Google Scholar]
  24. Farooq R.K. Alamoudi W. Alhibshi A. Rehman S. Sharma A.R. Abdulla F.A. Varied composition and underlying mechanisms of gut microbiome in neuroinflammation. Microorganisms 2022 10 4 705 10.3390/microorganisms10040705 35456757
    [Google Scholar]
  25. Ushakova V.M. Morozova A.Yu. Reznik A.M. Kostyuk G.P. Chekhonin V.P. Molecular biological aspects of depressive disorders: A modern view. Mol. Biol. 2020 54 5 725 749 33009787
    [Google Scholar]
  26. Boehme M. van de Wouw M. Bastiaanssen T.F.S. Mid-life microbiota crises: Middle age is associated with pervasive neuroimmune alterations that are reversed by targeting the gut microbiome. Mol. Psychiatry 2020 25 10 2567 2583 10.1038/s41380‑019‑0425‑1 31092898
    [Google Scholar]
  27. Sudo N. Chida Y. Aiba Y. Postnatal microbial colonization programs the hypothalamic–pituitary–adrenal system for stress response in mice. J. Physiol. 2004 558 1 263 275 10.1113/jphysiol.2004.063388 15133062
    [Google Scholar]
  28. Tan X. Letendre J.H. Collins J.J. Wong W.W. Synthetic biology in the clinic: Engineering vaccines, diagnostics, and therapeutics. Cell 2021 184 4 881 898 10.1016/j.cell.2021.01.017 33571426
    [Google Scholar]
  29. Kaji T. Arito M. Tsutiya A. Layilin enhances the invasive ability of malignant glioma cells via SNAI1 signaling. Brain Res. 2019 1719 140 147 10.1016/j.brainres.2019.05.034 31145904
    [Google Scholar]
  30. Corti D. Purcell L.A. Snell G. Veesler D. Tackling COVID-19 with neutralizing monoclonal antibodies. Cell 2021 184 17 4593 4595 10.1016/j.cell.2021.07.027 34416148
    [Google Scholar]
  31. Zhang L. Wu H. Zhao M. Chang C. Lu Q. Clinical significance of miRNAs in autoimmunity. J. Autoimmun. 2020 109 102438 10.1016/j.jaut.2020.102438 32184036
    [Google Scholar]
  32. Skalny A.V. Aschner M. Santamaria A. The role of gut microbiota in the neuroprotective effects of selenium in Alzheimer’s disease. Mol. Neurobiol. 2025 62 2 1675 1692 39012446
    [Google Scholar]
  33. Carabotti M. Scirocco A. Maselli M.A. Severi C. The gut-brain axis: Interactions between enteric microbiota, central and enteric nervous systems. Ann. Gastroenterol. 2015 28 2 203 209 25830558
    [Google Scholar]
  34. Zheng Y. Bonfili L. Wei T. Eleuteri A.M. Understanding the gut–brain axis and its therapeutic implications for neurodegenerative disorders. Nutrients 2023 Oct 31 15 21 4631 10.3390/nu15214631
    [Google Scholar]
  35. Zhang H. Chen Y. Wang Z. Implications of Gut Microbiota in Neurodegenerative Diseases. Front. Immunol. 2022 13 785644 10.3389/fimmu.2022.785644 35237258
    [Google Scholar]
  36. Forsythe P. Bienenstock J. Kunze W.A. Vagal pathways for microbiome-brain-gut axis communication. Adv. Exp. Med. Biol. 2014 817 115 133 10.1007/978‑1‑4939‑0897‑4_5 24997031
    [Google Scholar]
  37. Strandwitz P. Neurotransmitter modulation by the gut microbiota. Brain Res. 2018 1693 128 133
    [Google Scholar]
  38. Breit S. Kupferberg A. Rogler G. Hasler G. Vagus nerve as modulator of the brain–gut axis in psychiatric and inflammatory disorders. Front. Psychiatry 2018 9 44 10.3389/fpsyt.2018.00044 29593576
    [Google Scholar]
  39. Appleton J. The gut-brain axis: Influence of microbiota on mood and mental health. Integr. Med. 2018 17 4 28 32 31043907
    [Google Scholar]
  40. Mayer E.A. Savidge T. Shulman R.J. Brain-gut microbiome interactions and functional bowel disorders. Gastroenterology 2014 146 6 1500 1512 10.1053/j.gastro.2014.02.037 24583088
    [Google Scholar]
  41. McVey Neufeld K.A. Mao Y.K. Bienenstock J. Foster J.A. Kunze W.A. The microbiome is essential for normal gut intrinsic primary afferent neuron excitability in the mouse. Neurogastroenterol. Motil. 2013 25 2 183 e88 10.1111/nmo.12049 23181420
    [Google Scholar]
  42. O’Riordan K.J. Collins M.K. Moloney G.M. Short chain fatty acids: Microbial metabolites for gut-brain axis signalling. Mol. Cell. Endocrinol. 2022 546 111572 10.1016/j.mce.2022.111572 35066114
    [Google Scholar]
  43. Abdelhalim K.A. Short-chain fatty acids (SCFAs) from gastrointestinal disorders, metabolism, epigenetics, central nervous system to cancer - A mini-review. Chem. Biol. Interact. 2024 388 110851 10.1016/j.cbi.2023.110851 38145797
    [Google Scholar]
  44. Høverstad T. Midtvedt T. Short-chain fatty acids in germfree mice and rats. J Nutr 1986 116 9 1772 6 https://pubmed.ncbi.nlm.nih. gov/3761032/ 10.1093/jn/116.9.1772 3761032
    [Google Scholar]
  45. Wu J. Lu X. Yan C. Neuro-immune-cancer interactions: Mechanisms and therapeutic implications for tumor modulation. Brain Behavior and Immunity Integrative 2025 April 1 10 100119
    [Google Scholar]
  46. van der Hee B. Wells J.M. Microbial regulation of host physiology by short-chain fatty acids. Trends Microbiol. 2021 29 8 700 712 10.1016/j.tim.2021.02.001 33674141
    [Google Scholar]
  47. Roy D. Modi A. Ghosh R. Ghosh R. Benito-León J. Visceral adipose tissue molecular networks and regulatory microRNA in pediatric obesity: An in silico approach. Int. J. Mol. Sci. 2022 23 19 11036 10.3390/ijms231911036 36232337
    [Google Scholar]
  48. Fröhlich E.E. Farzi A. Mayerhofer R. Cognitive impairment by antibiotic-induced gut dysbiosis: Analysis of gut microbiota-brain communication. Brain Behav. Immun. 2016 56 140 155 10.1016/j.bbi.2016.02.020 26923630
    [Google Scholar]
  49. Mu C. Yang Y. Zhu W. Gut microbiota: The brain peacekeeper. Front. Microbiol. 2016 7 345 10.3389/fmicb.2016.00345 27014255
    [Google Scholar]
  50. Rios-Covian D. González S. Nogacka A.M. An overview on fecal branched short-chain fatty acids along human life and as related with body mass index: Associated dietary and anthropometric factors. Front. Microbiol. 2020 11 973 10.3389/fmicb.2020.00973 32547507
    [Google Scholar]
  51. Shin Y. Han S. Kwon J. Roles of short-chain fatty acids in inflammatory bowel disease. Nutrients 2023 15 20 4466 10.3390/nu15204466 37892541
    [Google Scholar]
  52. Mancusi R. Monje M. The neuroscience of cancer. Nature 2023 Jun 15 618 7965 467 479
    [Google Scholar]
  53. Akhtar M. Chen Y. Ma Z. Gut microbiota-derived short chain fatty acids are potential mediators in gut inflammation. Anim. Nutr. 2022 8 350 360 10.1016/j.aninu.2021.11.005 35510031
    [Google Scholar]
  54. O’Keefe S.J.D. Diet, microorganisms and their metabolites, and colon cancer. Nature. Rev. Gastroenterol. Hepatol. 2016 13 12 691 706 10.1038/nrgastro.2016.165
    [Google Scholar]
  55. Gaudier E. Rival M. Buisine M.P. Robineau I. Hoebler C. Butyrate enemas upregulate Muc genes expression but decrease adherent mucus thickness in mice colon. Physiol. Res. 2009 58 1
    [Google Scholar]
  56. Peng L. Li Z.R. Green R.S. Holzmanr I.R. Lin J. Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers. J. Nutr. 2009 139 9 1619 1625 10.3945/jn.109.104638 19625695
    [Google Scholar]
  57. Lewis K. Lutgendorff F. Enhanced translocation of bacteria across metabolically stressed epithelia is reduced by butyrate. Inflamm. Bowel Dis. 2010 Jul 16 7 1138 1148 10.1002/ibd.21177 20024905
    [Google Scholar]
  58. Liu L. Wang H. Chen X. Zhang Y. Zhang H. Xie P. Gut microbiota and its metabolites in depression: From pathogenesis to treatment. EBioMedicine 2023 90 104527 10.1016/j.ebiom.2023.104527 36963238
    [Google Scholar]
  59. Gao Y. Yao Q. Meng L. Wang J. Zheng N. Double-side role of short chain fatty acids on host health via the gut-organ axes. Anim. Nutr. 2024 18 322 339 10.1016/j.aninu.2024.05.001 39290857
    [Google Scholar]
  60. Frost G. Sleeth M.L. Sahuri-Arisoylu M. The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. Nat. Commun. 2014 5 1 3611 10.1038/ncomms4611 24781306
    [Google Scholar]
  61. Clarke G. Stilling R.M. Kennedy P.J. Stanton C. Cryan J.F. Dinan T.G. Minireview: Gut microbiota: The neglected endocrine organ Mol Endocrinol 2014 28 8 1221 38 https://pubmed.ncbi.nlm.nih.gov/24892638/ 10.1210/me.2014‑1108 24892638
    [Google Scholar]
  62. Nankova B.B. Agarwal R. MacFabe D.F. La Gamma E.F. Enteric bacterial metabolites propionic and butyric acid modulate gene expression, including CREB-dependent catecholaminergic neurotransmission, in PC12 cells--possible relevance to autism spectrum disorders. PLoS One 2014 9 8 e103740 10.1371/journal.pone.0103740 25170769
    [Google Scholar]
  63. Cervenka I. Agudelo L.Z. Ruas J.L. Kynurenines: Tryptophan’s metabolites in exercise, inflammation, and mental health. Science 2017 357 6349 eaaf9794 10.1126/science.aaf9794 28751584
    [Google Scholar]
  64. Cui Y. Yang Y. Ni Z. Astroglial Kir4.1 in the lateral habenula drives neuronal bursts in depression. Nature 2018 554 7692 323 327 10.1038/nature25752 29446379
    [Google Scholar]
  65. Köhler C.A. Freitas T.H. Maes M. Peripheral cytokine and chemokine alterations in depression: A meta‐analysis of 82 studies. Acta Psychiatr. Scand. 2017 135 5 373 387 10.1111/acps.12698 28122130
    [Google Scholar]
  66. Raison C.L. Capuron L. Miller A.H. Cytokines sing the blues: Inflammation and the pathogenesis of depression. Trends Immunol. 2006 27 1 24 31 10.1016/j.it.2005.11.006 16316783
    [Google Scholar]
  67. Kopczyńska J. Kowalczyk M. The potential of short-chain fatty acid epigenetic regulation in chronic low-grade inflammation and obesity. Front. Immunol. 2024 15 1380476 10.3389/fimmu.2024.1380476 38605957
    [Google Scholar]
  68. Yao Y. Cai X. Fei W. Ye Y. Zhao M. Zheng C. The role of short-chain fatty acids in immunity, inflammation and metabolism. Crit. Rev. Food Sci. Nutr. 2022 62 1 1 12 10.1080/10408398.2020.1854675 33261516
    [Google Scholar]
  69. Corrêa-Oliveira R. Fachi J.L. Vieira A. Sato F.T. Vinolo M.A.R. Regulation of immune cell function by short‐chain fatty acids. Clin. Transl. Immunology 2016 5 4 e73 10.1038/cti.2016.17 27195116
    [Google Scholar]
  70. Donohoe D.R. Garge N. Zhang X. The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. Cell Metab. 2011 13 5 517 526 10.1016/j.cmet.2011.02.018 21531334
    [Google Scholar]
  71. Rosa J.M. Formolo D.A. Yu J. Lee T.H. Yau S. The role of MicroRNA and Microbiota in depression and anxiety. Front. Behav. Neurosci. 2022 16 828258 10.3389/fnbeh.2022.828258 35299696
    [Google Scholar]
  72. Wang Y. Yan Y. Wei J. Down-regulated miR-16-2 in peripheral blood is positively correlated with decreased bilateral insula volume in patients with major depressive disorder. J. Affect. Disord. 2023 338 137 143 10.1016/j.jad.2023.05.068 37245547
    [Google Scholar]
  73. Ding Y. Zhong M. Qiu B. Liu C. Wang J. Liang J. Abnormal expression of miR 135a in patients with depression and its possible involvement in the pathogenesis of the condition. Exp. Ther. Med. 2021 22 1 726 10.3892/etm.2021.10158 34007335
    [Google Scholar]
  74. Dwivedi Y. Emerging role of microRNAs in major depressive disorder: Diagnosis and therapeutic implications. Dialogues Clin. Neurosci. 2014 16 1 43 61 10.31887/DCNS.2014.16.1/ydwivedi 24733970
    [Google Scholar]
  75. Sun Z. Zhan H. Wang C. Guo P. Shanzhiside methylester protects against depression by inhibiting inflammation via the miRNA-155-5p/SOCS1 axis. Psychopharmacology 2022 239 7 2201 2213 10.1007/s00213‑022‑06107‑7 35294601
    [Google Scholar]
  76. Cai L. Xu J. Liu J. miRNAs in treatment-resistant depression: A systematic review. Mol. Biol. Rep. 2024 51 1 638 10.1007/s11033‑024‑09554‑x 38727891
    [Google Scholar]
  77. Wu X. Zhang Y. Wang P. Clinical and preclinical evaluation of miR‐144‐5p as a key target for major depressive disorder. CNS Neurosci. Ther. 2023 29 11 3598 3611 10.1111/cns.14291 37308778
    [Google Scholar]
  78. Chudzik A. Orzyłowska A. Rola R. Stanisz G.J. Probiotics, prebiotics and postbiotics on mitigation of depression symptoms: Modulation of the brain–gut–microbiome axis. Biomolecules 2021 11 7 1000 10.3390/biom11071000 34356624
    [Google Scholar]
  79. Zhang H.P. Circulating microRNA 134 sheds light on the diagnosis of major depressive disorder. Transl. Psychiatry 2020 10 1 95
    [Google Scholar]
  80. Zhang X. Xue Y. Li J. The involvement of ADAR1 in antidepressant action by regulating BDNF via miR-432. Behav. Brain Res. 2021 402 113087 10.1016/j.bbr.2020.113087 33412228
    [Google Scholar]
  81. Zhang X. Yan W. Xue Y. Roles of miR-432 and circ_0000418 in mediating the anti-depressant action of ADAR1. Neurobiol. Stress 2021 15 100396 10.1016/j.ynstr.2021.100396 34568523
    [Google Scholar]
  82. Brás J.P. Pinto S. von Doellinger O. Combining inflammatory miRNA molecules as diagnostic biomarkers for depression: A clinical study. Front. Psychiatry 2023 14 1227618 10.3389/fpsyt.2023.1227618 37575572
    [Google Scholar]
  83. Mallick R. Basak S. Das R.K. Roles of the gut microbiota in human neurodevelopment and adult brain disorders. Front. Neurosci. 2024 18 1446700 10.3389/fnins.2024.1446700 39659882
    [Google Scholar]
  84. Saba R. Sorensen D.L. Booth S.A. MicroRNA-146a: A dominant, negative regulator of the innate immune response. Front. Immunol. 2014 5 578 10.3389/fimmu.2014.00578 25484882
    [Google Scholar]
  85. Meisgen F. Xu Landén N. Wang A. MiR-146a negatively regulates TLR2-induced inflammatory responses in keratinocytes. J. Invest. Dermatol. 2014 134 7 1931 1940 10.1038/jid.2014.89 24670381
    [Google Scholar]
  86. Kaurani L. Clinical insights into MicroRNAs in depression: Bridging molecular discoveries and therapeutic potential. Int. J. Mol. Sci. 2024 25 5 2866 10.3390/ijms25052866 38474112
    [Google Scholar]
  87. Zhang Y. Zhao Y. Tian C. Wang J. Li W. Zhong C. Differential exosomal microRNA profile in the serum of a patient with depression. Eur. J. Psychiatry 2018 32 3 105 112 10.1016/j.ejpsy.2017.10.002
    [Google Scholar]
  88. Miao C. Chang J. The important roles of microRNAs in depression: New research progress and future prospects. J. Mol. Med. 2021 99 5 619 636 10.1007/s00109‑021‑02052‑8 33641067
    [Google Scholar]
  89. Hansen K.F. Obrietan K. MicroRNA as therapeutic targets for treatment of depression. Neuropsychiatr. Dis. Treat. 2013 9 1011 1021 23935365
    [Google Scholar]
  90. Zhang S. Ning X.M. Ding C. Zhang X.S. A novel microRNA and transcription factor mediated regulatory network in schizophrenia. BMC Syst. Biol. 2010 4 10 10.1186/1752‑0509‑4‑10 20156358
    [Google Scholar]
  91. Zhang L. Zhang L. Chen H. Xu X. The interplay between cytokines and microRNAs to regulate metabolic disorders. J. Interferon Cytokine Res. 2024 44 8 337 348 10.1089/jir.2024.0059 39082185
    [Google Scholar]
  92. Liu Y. Chen H. Feng L. Zhang J. Interactions between gut microbiota and metabolites modulate cytokine network imbalances in women with unexplained miscarriage. NPJ Biofilms Microbiomes 2021 7 1 24 10.1038/s41522‑021‑00199‑3 33731680
    [Google Scholar]
  93. Souza P.B. de Araujo Borba L. Castro de Jesus L. Valverde A.P. Gil-Mohapel J. Rodrigues A.L.S. Major depressive disorder and gut microbiota: Role of physical exercise. Int. J. Mol. Sci. 2023 24 23 16870 10.3390/ijms242316870 38069198
    [Google Scholar]
  94. Eltokhi A. Sommer I.E. A reciprocal link between gut microbiota, inflammation and depression: A place for probiotics? Front. Neurosci. 2022 16 852506 10.3389/fnins.2022.852506 35546876
    [Google Scholar]
  95. Maeng S.H. Hong H. Inflammation as the potential basis in depression. Int. Neurourol. J. 2019 23 S63 S71 10.5213/inj.1938226.113 31795605
    [Google Scholar]
  96. Singh R. Zogg H. Ro S. Role of microRNAs in disorders of gut–brain interactions: Clinical insights and therapeutic alternatives. J. Pers. Med. 2021 11 10 1021 10.3390/jpm11101021 34683162
    [Google Scholar]
  97. Sonoyama K. Ohsaka F. Role of microRNAs in the crosstalk between the gut microbiota and intestinal immune system. Biosci. Microbiota Food Health 2023 42 4 222 228 10.12938/bmfh.2023‑027 37791343
    [Google Scholar]
  98. Chen S. Li M. Tong C. Regulation of miRNA expression in the prefrontal cortex by fecal microbiota transplantation in anxiety-like mice. Front. Psychiatry 2024 15 1323801 10.3389/fpsyt.2024.1323801 38410679
    [Google Scholar]
  99. Salvi V. Gianello V. Tiberio L. Sozzani S. Bosisio D. Cytokine targeting by miRNAs in autoimmune diseases. Front. Immunol. 2019 10 15 10.3389/fimmu.2019.00015 30761124
    [Google Scholar]
  100. Ortega M.A. Alvarez-Mon M.A. García-Montero C. MicroRNAs as critical biomarkers of major depressive disorder: A comprehensive perspective. Biomedicines 2021 9 11 1659 10.3390/biomedicines9111659 34829888
    [Google Scholar]
  101. Wallace C.J.K. Milev R. The effects of probiotics on depressive symptoms in humans: A systematic review. Ann. Gen. Psychiatry 2017 16 1 14 10.1186/s12991‑017‑0138‑2 28239408
    [Google Scholar]
  102. Meng Y. Sun J. Zhang G. Pick fecal microbiota transplantation to enhance therapy for major depressive disorder. Prog. Neuropsychopharmacol. Biol. Psychiatry 2024 128 110860 10.1016/j.pnpbp.2023.110860 37678703
    [Google Scholar]
  103. Cheng J. Hu H. Ju Y. Gut microbiota-derived short-chain fatty acids and depression: Deep insight into biological mechanisms and potential applications. Gen. Psychiatr. 2024 37 1 e101374 10.1136/gpsych‑2023‑101374 38390241
    [Google Scholar]
  104. Yao S. Zhang M. Dong S.S. Wang J.H. Zhang K. Guo J. Bidirectional two-sample Mendelian randomization analysis identifies causal associations between relative carbohydrate intake and depression. Nat. Hum. Behav. 2022 6 11 1569 1576 10.1038/s41562‑022‑01412‑9 35851841
    [Google Scholar]
  105. Burokas A. Arboleya S. Moloney R.D. Targeting the microbiota-gut-brain axis: Prebiotics have anxiolytic and antidepressant-like effects and reverse the impact of chronic stress in mice. Biol. Psychiatry 2017 82 7 472 487 10.1016/j.biopsych.2016.12.031 28242013
    [Google Scholar]
  106. Haghighat N. Rajabi S. Mohammadshahi M. Effect of synbiotic and probiotic supplementation on serum brain-derived neurotrophic factor level, depression and anxiety symptoms in hemodialysis patients: A randomized, double-blinded, clinical trial. Nutr. Neurosci. 2021 24 6 490 499 10.1080/1028415X.2019.1646975 31379269
    [Google Scholar]
  107. Kumar A. Pramanik J. Goyal N. Gut Microbiota in anxiety and depression: Unveiling the relationships and management options. Pharmaceuticals 2023 16 4 565 10.3390/ph16040565 37111321
    [Google Scholar]
  108. Wu L. Ran L. Wu Y. Oral administration of 5-hydroxytryptophan restores gut microbiota dysbiosis in a mouse model of depression. Front. Microbiol. 2022 13 864571 10.3389/fmicb.2022.864571 35572711
    [Google Scholar]
  109. Robertson R.C. Seira Oriach C. Murphy K. Omega-3 polyunsaturated fatty acids critically regulate behaviour and gut microbiota development in adolescence and adulthood. Brain Behav. Immun. 2017 59 21 37 10.1016/j.bbi.2016.07.145 27423492
    [Google Scholar]
  110. Réus G.Z. Maciel A.L. Abelaira H.M. ω-3 and folic acid act against depressive-like behavior and oxidative damage in the brain of rats subjected to early- or late-life stress. Nutrition 2018 53 120 133 10.1016/j.nut.2018.03.006 29783176
    [Google Scholar]
  111. Allan N.P. Yamamoto B.Y. Kunihiro B.P. Ketogenic diet induced shifts in the gut microbiome associate with changes to inflammatory cytokines and brain-related miRNAs in children with autism spectrum disorder. Nutrients 2024 16 10 1401 10.3390/nu16101401 38794639
    [Google Scholar]
  112. Sánchez-Villegas A. Delgado-Rodríguez M. Alonso A. Association of the Mediterranean dietary pattern with the incidence of depression: The Seguimiento Universidad de Navarra/University of Navarra follow-up (SUN) cohort. Arch. Gen. Psychiatry 2009 66 10 1090 1098 10.1001/archgenpsychiatry.2009.129 19805699
    [Google Scholar]
  113. Féart C. Samieri C. Rondeau V. Adherence to a Mediterranean diet, cognitive decline, and risk of dementia. JAMA 2009 302 6 638 648 10.1001/jama.2009.1146 19671905
    [Google Scholar]
  114. Averina O.V. Poluektova E.U. Zorkina Y.A. Kovtun A.S. Danilenko V.N. Human gut microbiota for diagnosis and treatment of depression. Int. J. Mol. Sci. 2024 25 11 5782 10.3390/ijms25115782 38891970
    [Google Scholar]
  115. Poluektova E. Yunes R. Danilenko V. The putative antidepressant mechanisms of probiotic bacteria: Relevant genes and proteins. Nutrients 2021 13 5 1591 10.3390/nu13051591 34068669
    [Google Scholar]
  116. Alli S.R. Gorbovskaya I. Liu J.C.W. Kolla N.J. Brown L. Müller D.J. The gut microbiome in depression and potential benefit of prebiotics, probiotics and synbiotics: A systematic review of clinical trials and observational studies. Int. J. Mol. Sci. 2022 23 9 4494 10.3390/ijms23094494 35562885
    [Google Scholar]
  117. Inamdar A. Palled M.S. Suryawanshi S.S. Shetti P. Sharma H. A simple, cost-efficient stability-indicating RP-HPLC method for simultaneous estimation of embelin and piperine for routine analysis of marketed polyherbal capsules and tablets. Nat. Prod. Res. 2025 1 11 10.1080/14786419.2024.2448842 39780606
    [Google Scholar]
  118. Inamdar A. Gurupadayya B. Sharma H. The role of glial cells in autism spectrum disorder: Molecular mechanisms and therapeutic approaches. CNS Neurol. Disord. Drug Targets 2025 24 1 20 10.2174/0118715273337007241115102118 39773050
    [Google Scholar]
  119. Chandra P. Rastogi V. Porwal M. Sharma H. Verma A. Sachan N. A critical review on lipid nanoparticle-based siRNA formulations for breast cancer management. Pharm. Nanotechnol. 2024 13 1 19 10.2174/0122117385330006241120084721 39670497
    [Google Scholar]
  120. Kumari A Bajwa N Tamana From lab bench to bedside: Advancing malaria treatments through research, patents, and clinical trials. Curr. Treat. Options Infect. Dis. 2024 17 1 4 10.1007/s40506‑024‑00279‑w
    [Google Scholar]
  121. Al Noman A. Dev Sharma P. Jahin Mim T. Al Azad M. Sharma H. Molecular docking and ADMET analysis of coenzyme Q10 as a potential therapeutic agent for Alzheimer’s disease. Aging Pathobiol Ther 2024 6 4 1 13 10.31491/APT.2024.12.155
    [Google Scholar]
  122. Inamdar A. Gurupadayya B. Halagali P. Unraveling neurological drug delivery: Polymeric nanocarriers for enhanced blood-brain barrier penetration. Curr. Drug Targets 2024 26 1 24 10.2174/0113894501339455241101065040 39513304
    [Google Scholar]
  123. Mishra R. Kaur V. Nogai L. Emerging insights and novel therapeutics in polycystic ovary syndrome. Biochem. Cell. Arch. 2024 24 2 1613 1626 10.51470/bca.2024.24.2.1613
    [Google Scholar]
  124. Inamdar A. Gurupadayya B. Halagali P. Cutting-edge strategies for overcoming therapeutic barriers in Alzheimer’s disease. Curr. Pharm. Des. 2024 1 21 10.2174/0113816128344571241018154506 39492772
    [Google Scholar]
  125. Al Noman A. Afrosa H. Lihu I.K. Vitamin D and neurological health: Unraveling risk factors, disease progression, and treatment potential. CNS Neurol. Disord. Drug Targets 2024 24 1 12 10.2174/0118715273330972241009092828 39440730
    [Google Scholar]
  126. Chandra P. Porwal M. Rastogi V. Tyagi S.J. Sharma H. Verma A. Carb‐loaded passion: A comprehensive exploration of carbohydrates in shaping aphrodisiac effects. Macromol. Symp. 2024 413 5 2400064 10.1002/masy.202400064
    [Google Scholar]
  127. Sarkar S. Bhui U. Kumar B. Correlation between cognitive impairment and peripheral biomarkers - Significance of phosphorylated Tau and Amyloid-β in Alzheimer’s disease: A new insight. Curr Psychiatry Res Rev 2024 21 1 25 10.2174/0126660822329981241007105405
    [Google Scholar]
  128. Pathak R. Sharma H. Chandra P. Halagali P. Ali Z. A compressive review: Mechanisms underlying the use of diuretics in the treatment of hypertension. Indian J Nat Sci 2024 15 85 78063 78075
    [Google Scholar]
  129. Sharma H. Chandra P. Pathak R. Bhandari M. Arushi S.V. Advancements in the therapeutic approaches to treat neurological disorders. Cah Magellanes-NS 2024 6 2 4328 4389
    [Google Scholar]
  130. Chandra P. Sharma H. Phosphodiesterase inhibitors for treatment of Alzheimer’s disease. Indian Drugs 2024 61 7 7 22 10.53879/id.61.07.14382
    [Google Scholar]
  131. Pathak R. Sharma S. Bhandari M. Neuroinflammation at the crossroads of metabolic and neurodegenerative diseases: Causes, consequences and interventions. J. Exp. Zool. India 2024 21 2 2447 2461 10.59467/jez.2024.27.2.2447
    [Google Scholar]
  132. Singh A. Kumar P. Sharma H. Breakthrough opportunities of nanotheranostics in psoriasis: From pathogenesis to management strategy. Infect. Disord. Drug Targets 2025 24 1 20 10.2174/0118715265298802240603120251 39075964
    [Google Scholar]
  133. Sharma H. Tyagi S.J. Varshney P. Pathak N. Pathak R. A review on Mpox: Diagnosis, prevention and treatments. Coronaviruses 2024 5 1 17 10.2174/0126667975301557240604113752
    [Google Scholar]
  134. Sharma H. Halagali P. Majumder A. Sharma V. Pathak R. Natural compounds targeting signaling pathways in breast cancer therapy. African J Biol Sci 2024 6 10 5430 5479 10.33472/AFJBS.6.10.2024.5430‑5479
    [Google Scholar]
  135. Sharma H. Pathak R. Biswas D. Unveiling the therapeutic potential of modern probiotics in addressing neurodegenerative disorders: A comprehensive exploration, review and future perspectives on intervention strategies. Curr Psychiatry Res Rev 2024 20 10.2174/0126660822304321240520075036
    [Google Scholar]
  136. Pathak R. Kaur V. Sharma S. Bhandari M. Mishra R. Saxena A. Pazopanib: Effective monotherapy for precise cancer treatment, targeting specific mutations and tumors. AfrJBioSc 2024 6 9 1311 1330 10.33472/AFJBS.6.9.2024.1311‑1330
    [Google Scholar]
  137. Kapoor D.U. Sharma H. Maheshwari R. Konjac glucomannan: A comprehensive review of its extraction, health benefits, and pharmaceutical applications. Carbohydr. Polym. 2024 339 122266 10.1016/j.carbpol.2024.122266 38823930
    [Google Scholar]
  138. Chandra P. Ali Z. Fatima N. Sharma H. Sachan N. Sharma K.K. Shankhpushpi (Convolvulus pluricaulis): Exploring its cognitive enhancing mechanisms and therapeutic potential in neurodegenerative disorders. Curr. Bioact. Compd. 2025 21 2 E290424229510 10.2174/0115734072292339240416095600
    [Google Scholar]
  139. Kumar P. Sharma H. Singh A. Targeting the interplay of proteins through PROTACs for management cancer and associated disorders. Curr. Cancer Ther. Rev. 2024 20 10.2174/0115733947304806240417092449
    [Google Scholar]
  140. Sharma H. Chandra P. Effects of natural remedies on memory loss and Alzheimer’s disease. AfrJBioSc 2024 6 7 187 211 10.33472/AFJBS.6.7.2024.187‑211
    [Google Scholar]
  141. Halagali P. Inamdar A. Singh J. Phytochemicals, herbal extracts, and dietary supplements for metabolic disease management. Endocr. Metab. Immune Disord. Drug Targets 2024 24 10.2174/0118715303287911240409055710 38676520
    [Google Scholar]
  142. Das S. Mukherjee T. Mohanty S. Impact of NF-κB signaling and Sirtuin-1 protein for targeted inflammatory intervention. Curr. Pharm. Biotechnol. 2025 26 8 1207 1220 10.2174/0113892010301469240409082212 38638042
    [Google Scholar]
  143. Sharma H. Kaushik M. Goswami P. Role of miRNAs in brain development. MicroRNA 2024 13 2 96 109 10.2174/0122115366287127240322054519 38571343
    [Google Scholar]
  144. Ashique S. Bhowmick M. Pal R. Multi drug resistance in Colorectal Cancer- Approaches to overcome, advancements and future success. Adv Cancer Biol Metastasis 2024 10 100114 10.1016/j.adcanc.2024.100114
    [Google Scholar]
  145. Ashique S. Pal R. Sharma H. Mishra N. Garg A. Unraveling the emerging niche role of Extracellular Vesicles (EVs) in Traumatic Brain Injury (TBI). CNS Neurol. Disord. Drug Targets 2024 23 11 1357 1370 10.2174/0118715273288155240201065041 38351688
    [Google Scholar]
  146. Kumar P. Pandey S. Ahmad F. Verma A. Sharma H. Ashique S. Carbon nanotubes: A targeted drug delivery against cancer cell. Curr. Nanosci. 2023 9 1 31 10.2174/0115734137271865231105070727
    [Google Scholar]
  147. Sharma H. Chandra P. Verma A. Pandey S.N. Kumar P. Sigh A. Therapeutic approaches of nutraceuticals in the prevention of neurological disorders. Eur. Chem. Bull. 2023 12 5 1575 1596 10.48047/ecb/2023.12.si5a.038
    [Google Scholar]
  148. Sharma H. Chandra P. Challenges and future prospects: A benefaction of phytoconstituents on molecular targets pertaining to Alzheimer’s disease. Int. J. Pharm. Investig. 2023 14 1 117 126 10.5530/ijpi.14.1.15
    [Google Scholar]
  149. Sharma H. Pathak R. Jain S. Ficus racemosa L: A review on its important medicinal uses, phytochemicals and biological activities. J. Popul. Ther. Clin. Pharmacol. 2023 30 17 213 227 10.47750/jptcp.2023.30.17.018
    [Google Scholar]
  150. Singh L.P. Gugulothu S. Perusomula R. Synthesis of some tetrazole and Thiazolidine-4-One derivatives of schiff base by using ionic liquids as catalyst and evaluation of their antifungal and antibacterial activity. Eur. Chem. Bull. 2023 12 8 281 297
    [Google Scholar]
  151. Sharma H. A brief review on pathogenesis, transmission and management of monkeypox virus outbreaks. Bull Environ Pharmacol Life Sci 2023 12 4 244 256
    [Google Scholar]
  152. Sharma H. Bhattacharya V. Bhatt A. Optimization of formulation by box Behnken and in-vitro studies of emulsified gel containing zaltoprofen for the management of arthritis. Eur. Chem. Bull. 2023 12 4 11734 11744
    [Google Scholar]
  153. Koli M. Nogai L. Bhandari M. Mishra R. Pathak R. Sharma H. Formulation And evaluation of berberine hydrochloride film coated tablet. J. Pharm. Negat. Results 2023 14 2 3439 3449 10.47750/pnr.2023.14.02.403
    [Google Scholar]
  154. Dwivedi M. Jha K.K. Pandey S. Sachan A. Sharma H. Dwivedi S.K. Formulation and evaluation of herbal medicated chocolate in treatment of intestinal worms and related problems. IJFANS 2022 11 2 1426 1439
    [Google Scholar]
  155. Sharma H. Pathak R. Kumar N. Endocannabinoid system: Role in depression, recompense, and pain control. J Surv Fish Sci 2023 10 4S 2743 2751 10.17762/sfs.v10i4S.1655
    [Google Scholar]
  156. Sharma H. Pathak R. Saxena D. Kumar N. Emerging role of non-coding RNA’S: Human health and diseases. GIS 2022 9 7 2022 2050
    [Google Scholar]
  157. Sharma H. Rani T. Khan S. An insight into neuropathic pain: A systemic and up-to-date review. Int. J. Pharm. Sci. Res. 2023 14 2 607 621 10.13040/IJPSR.0975‑8232.14(2).607‑21
    [Google Scholar]
  158. Pandey P. Kumar N. Kaur T. Saini S. Sharma H. Antidiabetic activity of caesalpinia bonducella leaves of hydro alcoholic extracts in albino rats. YMER Digital 2022 21 7 840 846 10.37896/YMER21.07/67
    [Google Scholar]
  159. Pathak R. Sharma H. Kumar N. A brief review on anthocephalus cadamba. Acta Scientific Pharmacology 2022 3 5
    [Google Scholar]
  160. Sharma S. Dinda S.C.S.H. Matrix types drug delivery system for sustained release : A review. ASIO J Drug Deliv 2022 6 1 1 8
    [Google Scholar]
  161. Sharma H. Pathak R. A review on prelimenary phytochemical screening of curcuma longa linn. ASIO J Pharma Herbal Med Res 2021 7 2 24 27
    [Google Scholar]
  162. Pathak R. Sharma H. A review on medicinal uses of Cinnamomum verum (Cinnamon). J. Drug Deliv. Ther. 2021 11 6-S 161 166 10.22270/jddt.v11i6‑S.5145
    [Google Scholar]
  163. Sharma H. Pande M. Jha K.K. Hyperuricemia: A risk factor beyond gout. J Pharm Herb Med Res 2020 6 1 42 49
    [Google Scholar]
  164. Sharma H. Singh S. Jha K.K. Treatment and recommendations for homeless patients with hypertension, hyperlipidemia & heart failure-A review. ASIO J Exp Pharmacol Clin Res 2020 6 1 24 32 10.2016‑37245516/;
    [Google Scholar]
  165. Sharma H. Kaushik M. Ashique S. Farid A. Taghizadeh-Hesary F. Evolving landscape on sex specific status on lung cancer management: Moderating effects, risk assessment. In: Emerging Social Issues on Targeted Drug Delivery. Scientific Research Publishing, Inc. 2024 189 220
    [Google Scholar]
  166. Suryawanshi M. Kurtkoti S. Mulla T. Shah E. Sharma H. Bhatt H. Edible Biopolymers for Food Applications. In: Green Biopolymers for Packaging Applications. Boca Raton CRC Press 2024 228 254 10.1201/9781003455356‑10
    [Google Scholar]
  167. Suryawanshi M. Mulla T. Suryawanshi I. Vinchurkar K. Kallawala U. Sharma H. Modified starch in food packaging. In: Green Biopolymers for Packaging Applications. Boca Raton CRC Press 2024 255 271 10.1201/9781003455356‑11
    [Google Scholar]
  168. Sharma H. Kaushik M. Venishaa S. Pathak R. Farid A. Bhowmick M. Correlation and successive role of synbiotics to manage blood pressure. In: Synbiotics in Metabolic Disorders. Boca Raton CRC Press 2024 103 120 10.1201/9781032702438‑7
    [Google Scholar]
  169. Ray P. Faseeh M.A. Adak D. Sharma H. Probiotics, prebiotics, and postbiotics on metabolic diseases targeting gut microbiota. In: Synbiotics in Metabolic Disorders. Boca Raton CRC Press 2024 160 172 10.1201/9781032702438‑11
    [Google Scholar]
  170. Chandra P. Sharma H. Sachan N. The potential role of prebiotics, probiotics, and synbiotics in cancer prevention and therapy. In: Synbiotics in Metabolic Disorders. Boca Raton CRC Press 2024 191 213 10.1201/9781032702438‑13
    [Google Scholar]
/content/journals/cgt/10.2174/0115665232361169250617192348
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Bridging Mind and Gut: The Molecular Mechanisms of microRNA, Microbiota, and Cytokine Interactions in Depression
Bentham Science Publishers ; https://doi.org/10.2174/0115665232361169250617192348
/content/journals/cgt/10.2174/0115665232361169250617192348
/content/journals/cgt/10.2174/0115665232361169250617192348
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  • Article Type:     Review Article
Keywords: cytokines ; nanomedicine ; MicroRNAs ; depression ; neuroinflammation ; microbiota

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