Exploration of Neuroscience

Table 1. Summary of mechanistic pathways.

Mitochondrial dysfunction	Pathophysiological mechanism	Neurobiological consequences of MDD
Impaired oxidative phosphorylation	Reduced ATP and synaptic energy	Cognitive and mood deficits
Oxidative stress and mtDNA damage	Excessive ROS and apoptosis	Neurodegeneration, neuronal loss
Altered fission/fusion dynamics	Fragmented mitochondria	Impaired plasticity, stress vulnerability
Defective mitophagy	Accumulation of damaged mitochondria	Chronic inflammation
Epigenetic dysregulation	Silencing of mitochondrial biogenesis genes	Reduced neurogenesis, metabolic failure

Return to article view

MDD: major depressive disorder; ATP: adenosine triphosphate; mtDNA: mitochondrial DNA; ROS: reactive oxygen species.

Declarations

Author contributions

OMA: Conceptualization. Data curation, Investigation, Writing—original draft, Writing—review & editing, Supervision. CAC, OEO, OCA, and ODA: Data curation, Investigation, Writing—review & editing. SJA: Writing—review & editing. All authors read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

Publisher’s note

Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

References

Depressive disorder (depression) [Internet]. World Health Organization; [cited 2026 Jan 20]. Available from: https://www.who.int/news-room/fact-sheets/detail/depression

Lin L, Guo Z, Ren Z, Feng Y, Fang P, Wang T, et al. Bibliometric insights into astrocytic roles in depression and treatment. Front Cell Neurosci. 2025;18:1521398. [DOI] [PubMed] [PMC]

McIntyre RS, Rosenblat JD, Nemeroff CB, Sanacora G, Murrough JW, Berk M, et al. Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation. Am J Psychiatry. 2021;178:383–99. [DOI] [PubMed] [PMC]

Marx W, Penninx BWJH, Solmi M, Furukawa TA, Firth J, Carvalho AF, et al. Major depressive disorder. Nat Rev Dis Primers. 2023;9:44. [DOI] [PubMed]

Góralczyk-Bińkowska A, Szmajda-Krygier D, Kozłowska E. The Microbiota-Gut-Brain Axis in Psychiatric Disorders. Int J Mol Sci. 2022;23:11245. [DOI] [PubMed] [PMC]

Acharjee P, Singh VV, Prasad SK, Thakur P, Acharjee A. Signaling Pathways and Gut–Brain Axis: Relationship in Neurological Disorders. In Biotics and the Gut-Brain Axis in Neurological Disorders. CRC Press; 2025. pp. 218–33.

Bakshi I, Dey S, Raut AJ, Katta S, Sharma P. Exploring the Gut-Brain Axis: A Comprehensive Review of Interactions Between the Gut Microbiota and the Central Nervous System. Int J Multidiscip Res. 2024;6:1–15.

Chudzik A, Orzyłowska A, Rola R, Stanisz GJ. Probiotics, Prebiotics and Postbiotics on Mitigation of Depression Symptoms: Modulation of the Brain-Gut-Microbiome Axis. Biomolecules. 2021;11:1000. [DOI] [PubMed] [PMC]

Bi C, Guo S, Hu S, Chen J, Ye M, Liu Z. The microbiota-gut-brain axis and its modulation in the therapy of depression: Comparison of efficacy of conventional drugs and traditional Chinese medicine approaches. Pharmacol Res. 2022;183:106372. [DOI] [PubMed]

10.

Mehta I, Juneja K, Nimmakayala T, Bansal L, Pulekar S, Duggineni D, et al. Gut Microbiota and Mental Health: A Comprehensive Review of Gut-Brain Interactions in Mood Disorders. Cureus. 2025;17:e81447. [DOI] [PubMed] [PMC]

11.

Casanova A, Wevers A, Navarro-Ledesma S, Pruimboom L. Mitochondria: It is all about energy. Front Physiol. 2023;14:1114231. [DOI] [PubMed] [PMC]

12.

Liu H, Wang S, Wang J, Guo X, Song Y, Fu K, et al. Energy metabolism in health and diseases. Signal Transduct Target Ther. 2025;10:69. [DOI] [PubMed] [PMC]

13.

Jiang M, Wang L, Sheng H. Mitochondria in depression: The dysfunction of mitochondrial energy metabolism and quality control systems. CNS Neurosci Ther. 2024;30:e14576. [DOI] [PubMed] [PMC]

14.

Chen H, Lu M, Lyu Q, Shi L, Zhou C, Li M, et al. Mitochondrial dynamics dysfunction: Unraveling the hidden link to depression. Biomed Pharmacother. 2024;175:116656. [DOI] [PubMed]

15.

Hesampour F, Bernstein CN, Ghia J. Brain-Gut Axis: Invasive and Noninvasive Vagus Nerve Stimulation, Limitations, and Potential Therapeutic Approaches. Inflamm Bowel Dis. 2024;30:482–95. [DOI] [PubMed]

16.

Xing X, Jiang Z, Tang X, Wang P, Li Y, Sun Y, et al. Sodium butyrate protects against oxidative stress in HepG2 cells through modulating Nrf2 pathway and mitochondrial function. J Physiol Biochem. 2016;73:405–14. [DOI] [PubMed]

17.

Mohamed Elfadil O, Mundi MS, Abdelmagid MG, Patel A, Patel N, Martindale R. Butyrate: More Than a Short Chain Fatty Acid. Curr Nutr Rep. 2023;12:255–62. [DOI] [PubMed]

18.

Yu M, Jia HM, Qin LL, Zou ZM. Gut microbiota and gut tissue metabolites involved in development and prevention of depression. J Affect Disord. 2022;297:8–17. [DOI] [PubMed]

19.

Zhu F, Tu H, Chen T. The Microbiota-Gut-Brain Axis in Depression: The Potential Pathophysiological Mechanisms and Microbiota Combined Antidepression Effect. Nutrients. 2022;14:2081. [DOI] [PubMed] [PMC]

20.

Irum N, Afzal T, Faraz MH, Aslam Z, Rasheed F. The role of gut microbiota in depression: an analysis of the gut-brain axis. Front Behav Neurosci. 2023;17:1185522. [DOI] [PubMed] [PMC]

21.

Sanada K, Nakajima S, Kurokawa S, Barceló-Soler A, Ikuse D, Hirata A, et al. Gut microbiota and major depressive disorder: A systematic review and meta-analysis. J Affect Disord. 2020;266:1–13. [DOI] [PubMed]

22.

Nie H, Ge J, Yang K, Peng Z, Wu H, Yang T, et al. Naotaifang III Protects Against Cerebral Ischemia Injury Through LPS/TLR4 Signaling Pathway in the Microbiota-Gut-Brain Axis. Drug Des Devel Ther. 2023;17:3571–88. [DOI] [PubMed] [PMC]

23.

Longo S, Rizza S, Federici M. Microbiota-gut-brain axis: relationships among the vagus nerve, gut microbiota, obesity, and diabetes. Acta Diabetol. 2023;60:1007–17. [DOI] [PubMed] [PMC]

24.

Mörkl S, Butler MI, Wagner-Skacel J. Gut-brain-crosstalk-the vagus nerve and the microbiota-gut-brain axis in depression. A narrative review. J Affect Disord Rep. 2023;13:100607. [DOI]

25.

Park JC, Chang L, Kwon HK, Im SH. Beyond the gut: decoding the gut-immune-brain axis in health and disease. Cell Mol Immunol. 2025;22:1287–312. [DOI] [PubMed] [PMC]

26.

Cui H, Wang N, Li H, Bian Y, Wen W, Kong X, et al. The dynamic shifts of IL-10-producing Th17 and IL-17-producing Treg in health and disease: a crosstalk between ancient “Yin-Yang” theory and modern immunology. Cell Commun Signal. 2024;22:99. [DOI] [PubMed] [PMC]

27.

Jenab A, Roghanian R, Emtiazi G. Bacterial Natural Compounds with Anti-Inflammatory and Immunomodulatory Properties (Mini Review). Drug Des Devel Ther. 2020;14:3787–801. [DOI] [PubMed] [PMC]

28.

Gryka-Marton M, Grabowska AD, Szukiewicz D. Breaking the Barrier: The Role of Proinflammatory Cytokines in BBB Dysfunction. Int J Mol Sci. 2025;26:3532. [DOI] [PubMed] [PMC]

29.

Kumar A, Pramanik J, Goyal N, Chauhan D, Sivamaruthi BS, Prajapati BG, et al. Gut Microbiota in Anxiety and Depression: Unveiling the Relationships and Management Options. Pharmaceuticals (Basel). 2023;16:565. [DOI] [PubMed] [PMC]

30.

Di Vincenzo F, Del Gaudio A, Petito V, Lopetuso LR, Scaldaferri F. Gut microbiota, intestinal permeability, and systemic inflammation: a narrative review. Intern Emerg Med. 2024;19:275–93. [DOI] [PubMed] [PMC]

31.

Jiao W, Lin J, Deng Y, Ji Y, Liang C, Wei S, et al. The immunological perspective of major depressive disorder: unveiling the interactions between central and peripheral immune mechanisms. J Neuroinflammation. 2025;22:10. [DOI] [PubMed] [PMC]

32.

Hwang YK, Oh JS. Interaction of the Vagus Nerve and Serotonin in the Gut-Brain Axis. Int J Mol Sci. 2025;26:1160. [DOI] [PubMed] [PMC]

33.

Pascaramadhani A, Septiani S, Basrowi RW, Sundjaya T. PREBIOTICS AND THE GUT-BRAIN AXIS: IMPLICATIONS FOR COGNITIVE DEVELOPMENT IN EARLY CHILDHOOD. J Indones Spec Nutr. 2025;3:103–13. [DOI]

34.

Arpaia N, Campbell C, Fan X, Dikiy S, van der Veeken J, deRoos P, et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature. 2013;504:451–5. [DOI] [PubMed] [PMC]

35.

Liu P, Liu Z, Wang J, Wang J, Gao M, Zhang Y, et al. Immunoregulatory role of the gut microbiota in inflammatory depression. Nat Commun. 2024;15:3003. [DOI] [PubMed] [PMC]

36.

Wang Y, Duan C, Du X, Zhu Y, Wang L, Hu J, et al. Vagus Nerve and Gut-Brain Communication. Neuroscientist. 2025;31:262–78. [DOI] [PubMed]

37.

Facchin S, Bertin L, Bonazzi E, Lorenzon G, De Barba C, Barberio B, et al. Short-Chain Fatty Acids and Human Health: From Metabolic Pathways to Current Therapeutic Implications. Life (Basel). 2024;14:559. [DOI] [PubMed] [PMC]

38.

Shi L, Jin L, Huang W. Bile Acids, Intestinal Barrier Dysfunction, and Related Diseases. Cells. 2023;12:1888. [DOI] [PubMed] [PMC]

39.

Calarge CA, Devaraj S, Shulman RJ. Gut permeability and depressive symptom severity in unmedicated adolescents. J Affect Disord. 2019;246:586–94. [DOI] [PubMed]

40.

Morys J, Małecki A, Nowacka-Chmielewska M. Stress and the gut-brain axis: an inflammatory perspective. Front Mol Neurosci. 2024;17:1415567. [DOI] [PubMed] [PMC]

41.

Singh SA, Vellapandian C. Structure of the Blood Brain Barrier and its Role in the Transporters for the Movement of Substrates across the Barriers. Curr Drug Metab. 2023;24:250–69. [DOI] [PubMed]

42.

Fisher D, Mentor S. Are claudin-5 tight-junction proteins in the blood-brain barrier porous? Neural Regen Res. 2020;15:1838–9. [DOI] [PubMed] [PMC]

43.

Wu H, Wang J, Teng T, Yin B, He Y, Jiang Y, et al. Biomarkers of intestinal permeability and blood-brain barrier permeability in adolescents with major depressive disorder. J Affect Disord. 2023;323:659–66. [DOI] [PubMed]

44.

Allen J, Romay-Tallon R, Brymer KJ, Caruncho HJ, Kalynchuk LE. Mitochondria and Mood: Mitochondrial Dysfunction as a Key Player in the Manifestation of Depression. Front Neurosci. 2018;12:386. [DOI] [PubMed] [PMC]

45.

Bansal Y, Kuhad A. Mitochondrial Dysfunction in Depression. Curr Neuropharmacol. 2016;14:610–8. [DOI] [PubMed] [PMC]

46.

Caruso G, Benatti C, Blom JMC, Caraci F, Tascedda F. The Many Faces of Mitochondrial Dysfunction in Depression: From Pathology to Treatment. Front Pharmacol. 2019;10:995. [DOI] [PubMed] [PMC]

47.

Song Y, Cao H, Zuo C, Gu Z, Huang Y, Miao J, et al. Mitochondrial dysfunction: A fatal blow in depression. Biomed Pharmacother. 2023;167:115652. [DOI] [PubMed]

48.

Scaini G, Mason BL, Diaz AP, Jha MK, Soares JC, Trivedi MH, et al. Dysregulation of mitochondrial dynamics, mitophagy and apoptosis in major depressive disorder: Does inflammation play a role? Mol Psychiatry. 2022;27:1095–102. [DOI] [PubMed]

49.

Valiente-Pallejà A, Tortajada J, Bulduk BK, Vilella E, Garrabou G, Muntané G, et al. Comprehensive summary of mitochondrial DNA alterations in the postmortem human brain: A systematic review. EBioMedicine. 2022;76:103815. [DOI] [PubMed] [PMC]

50.

Munshi S, Alarbi AM, Zheng H, Kuplicki R, Burrows K, Figueroa-Hall LK, et al. Increased expression of ER stress, inflammasome activation, and mitochondrial biogenesis-related genes in peripheral blood mononuclear cells in major depressive disorder. Mol Psychiatry. 2025;30:574–86. [DOI] [PubMed] [PMC]

51.

Ge Z, Hu Y, Kan W, Li L, Xu J, Zhang Y, et al. Lipid metabolic dysregulation-induced neuroinflammation in the pathophysiology of major depressive disorder. Front Immunol. 2025;16:1625087. [DOI] [PubMed] [PMC]

52.

Kalani K, Yan SF, Yan SS. Mitochondrial permeability transition pore: a potential drug target for neurodegeneration. Drug Discov Today. 2018;23:1983–9. [DOI] [PubMed] [PMC]

53.

Baev AY, Vinokurov AY, Potapova EV, Dunaev AV, Angelova PR, Abramov AY. Mitochondrial Permeability Transition, Cell Death and Neurodegeneration. Cells. 2024;13:648. [DOI] [PubMed] [PMC]

54.

Adell A. Brain NMDA Receptors in Schizophrenia and Depression. Biomolecules. 2020;10:947. [DOI] [PubMed] [PMC]

55.

Khan T, Waseem R, Zehra Z, Aiman A, Bhardwaj P, Ansari J, et al. Mitochondrial Dysfunction: Pathophysiology and Mitochondria-Targeted Drug Delivery Approaches. Pharmaceutics. 2022;14:2657. [DOI] [PubMed] [PMC]

56.

Han WM, Hao XB, Hong YX, Zhao SS, Chen XC, Wang R, et al. NMDARs antagonist MK801 suppresses LPS-induced apoptosis and mitochondrial dysfunction by regulating subunits of NMDARs via the CaM/CaMKII/ERK pathway. Cell Death Discov. 2023;9:59. [DOI] [PubMed] [PMC]

57.

Simon MS, Schiweck C, Arteaga-Henríquez G, Poletti S, Haarman BCM, Dik WA, et al. Monocyte mitochondrial dysfunction, inflammaging, and inflammatory pyroptosis in major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2021;111:110391. [DOI] [PubMed]

58.

Shi XN, Liu CY, Li L, Yao ML, Zhong Z, Jiang YM. The role and therapeutic potential of mitophagy in major depressive disorder. Front Pharmacol. 2025;16:1564276. [DOI] [PubMed] [PMC]

59.

Cardon I. Bridging depression and mitochondria: functional insights from cellular models in case study patients [dissertation]. Regensburg: Universität Regensburg; 2024. [DOI]

60.

Chen EZ, Clark RE. The microbiota-gut-brain axis: a new direction in research on depression. J Student Res. 2021;10:1–15. [DOI]

61.

Zhang S, Chen W, Ma C, Luo Y, Dong L, Hu X, et al. Role of microbiota-gut-brain axis in neurodegenerative diseases and the potential of microbiome-targeted dietary strategies: a review of current evidence and future perspective. Food Sci Hum Wellness. 2025;14:9250215. [DOI]

62.

Verma A, Bhagchandani T, Rai A, Nikita, Sardarni UK, Bhavesh NS, et al. Short-Chain Fatty Acid (SCFA) as a Connecting Link between Microbiota and Gut-Lung Axis-A Potential Therapeutic Intervention to Improve Lung Health. ACS Omega. 2024;9:14648–71. [DOI] [PubMed] [PMC]

63.

Rada-Iglesias A, Enroth S, Ameur A, Koch CM, Clelland GK, Respuela-Alonso P, et al. Butyrate mediates decrease of histone acetylation centered on transcription start sites and down-regulation of associated genes. Genome Res. 2007;17:708–19. [DOI] [PubMed] [PMC]

64.

Wu J, Zhou Z, Hu Y, Dong S. Butyrate-induced GPR41 activation inhibits histone acetylation and cell growth. J Genet Genomics. 2012;39:375–84. [DOI] [PubMed]

65.

Ma M, Zheng L, Yao X, Ma A, Chen Z, Li S, et al. Mushroom polysaccharides regulate diet-induced obesity by targeting lipid metabolism, gut microbiota and mitochondria. Food Sci Hum Wellness. 2025. [DOI]

66.

Li X, Wang C, Zhu J, Lin Q, Yu M, Wen J, et al. Sodium Butyrate Ameliorates Oxidative Stress-Induced Intestinal Epithelium Barrier Injury and Mitochondrial Damage through AMPK-Mitophagy Pathway. Oxid Med Cell Longev. 2022;2022:3745135. [DOI] [PubMed] [PMC]

67.

Cavaliere G, Catapano A, Trinchese G, Cimmino F, Penna E, Pizzella A, et al. Butyrate Improves Neuroinflammation and Mitochondrial Impairment in Cerebral Cortex and Synaptic Fraction in an Animal Model of Diet-Induced Obesity. Antioxidants (Basel). 2022;12:4. [DOI] [PubMed] [PMC]

68.

Suda K, Matsuda K. How Microbes Affect Depression: Underlying Mechanisms via the Gut-Brain Axis and the Modulating Role of Probiotics. Int J Mol Sci. 2022;23:1172. [DOI] [PubMed] [PMC]

69.

Guo Q, Li S, Xie Y, Zhang Q, Liu M, Xu Z, et al. The NAD+-dependent deacetylase, Bifidobacterium longum Sir2 in response to oxidative stress by deacetylating SigH (σH) and FOXO3a in Bifidobacterium longum and HEK293T cell respectively. Free Radic Biol Med. 2017;108:929–39. [DOI] [PubMed]

70.

Zhra M, Elahi MA, Tariq A, Abu-Zaid A, Yaqinuddin A. Sirtuins and Gut Microbiota: Dynamics in Health and a Journey from Metabolic Dysfunction to Hepatocellular Carcinoma. Cells. 2025;14:466. [DOI] [PubMed] [PMC]

71.

Tang BL. Sirt1 and the Mitochondria. Mol Cells. 2016;39:87–95. [DOI] [PubMed] [PMC]

72.

Perez Lao EJ, Fagerli E, Ferrier F, Young JI, Perez-Pinzon MA. Regulatory Dynamics of Nrf2 With Sirtuins in the Brain: Exploring Cellular Metabolism, Synaptic Plasticity, and Defense Mechanisms. J Neurochem. 2025;169:e70193. [DOI]

73.

Kim H, Kim H, Lee JH, Hwangbo C. Toll-like receptor 4 (TLR4): new insight immune and aging. Immun Ageing. 2023;20:67. [DOI] [PubMed] [PMC]

74.

Blevins HM, Xu Y, Biby S, Zhang S. The NLRP3 Inflammasome Pathway: A Review of Mechanisms and Inhibitors for the Treatment of Inflammatory Diseases. Front Aging Neurosci. 2022;14:879021. [DOI] [PubMed] [PMC]

75.

Fu J, Wu H. Structural Mechanisms of NLRP3 Inflammasome Assembly and Activation. Annu Rev Immunol. 2023;41:301–16. [DOI] [PubMed] [PMC]

76.

Jin HS, Suh HW, Kim SJ, Jo EK. Mitochondrial Control of Innate Immunity and Inflammation. Immune Netw. 2017;17:77–88. [DOI] [PubMed] [PMC]

77.

Dos Santos MP, Leocadio VE, de Sá Hayashide L, Marques M, Carvalho CF, Galina A, et al. Lipopolysaccharide Induces Mitochondrial Fragmentation and Energetic Shift in Reactive Microglia: Evidence for a Cell-Autonomous Program of Metabolic Plasticity. Toxins (Basel). 2025;17:293. [DOI] [PubMed] [PMC]

78.

Yang D, Wang Z, Chen Y, Guo Q, Dong Y. Interactions between gut microbes and NLRP3 inflammasome in the gut-brain axis. Comput Struct Biotechnol J. 2023;21:2215–27. [DOI] [PubMed] [PMC]

79.

Zhang JR, Shen SY, Zhai MY, Shen ZQ, Li W, Liang L, et al. Augmented microglial endoplasmic reticulum-mitochondria contacts mediate depression-like behavior in mice induced by chronic social defeat stress. Nat Commun. 2024;15:5199. [DOI] [PubMed] [PMC]

80.

Zhao W, Hu Y, Li C, Li N, Zhu S, Tan X, et al. Transplantation of fecal microbiota from patients with alcoholism induces anxiety/depression behaviors and decreases brain mGluR1/PKC ε levels in mouse. Biofactors. 2020;46:38–54. [DOI] [PubMed]

81.

Knudsen JK, Michaelsen TY, Bundgaard-Nielsen C, Nielsen RE, Hjerrild S, Leutscher P, et al. Faecal microbiota transplantation from patients with depression or healthy individuals into rats modulates mood-related behaviour. Sci Rep. 2021;11:21869. [DOI] [PubMed] [PMC]

82.

Strodl E, Bambling M, Parnam S, Ritchie G, Cramb S, Vitetta L. Probiotics and magnesium orotate for the treatment of major depressive disorder: a randomised double blind controlled trial. Sci Rep. 2024;14:20841. [DOI] [PubMed] [PMC]

83.

Lin SK, Kuo PH, Hsu CY, Chiu YH, Chen CH. The effects of Lactobacillus plantarum PS128 in patients with major depressive disorder: an eight-week double-blind, placebo-controlled study. Asian J Psychiatr. 2024;101:104210. [DOI] [PubMed]

84.

Hashemi-Mohammadabad N, Taghavi SA, Lambert N, Moshtaghi R, Bazarganipour F, Sharifi M. Adjuvant administration of probiotic effects on sexual function in depressant women undergoing SSRIs treatment: a double-blinded randomized controlled trial. BMC Psychiatry. 2024;24:44. [DOI] [PubMed] [PMC]

85.

Bahji A, Brietzke E, Cooke NCA, Clement F, Frey BN, Hofmeister M, et al. The Canadian Network for Mood and Anxiety Treatments Task Force Recommendations for the Use of Probiotics, Prebiotics, Synbiotics, and Fecal Microbiota Transplants in Adults With Major Depressive Disorder: Recommandations du Groupe de travail du Réseau canadien pour le traitement des troubles de l’humeur et de l’anxiété (Canadian Network for Mood and Anxiety Treatments, CANMAT) concernant l'utilisation des probiotiques, des prébiotiques, des symbiotiques et de la transplantation de microbiote fécal chez les adultes atteints de trouble dépressif majeur. Can J Psychiatry. 2026;71:346–58. [DOI] [PubMed] [PMC]

86.

Zu X, Xin J, Xie H, Xu X, Shen Y, Wang J, et al. Characteristics of gut microbiota and metabolic phenotype in patients with major depressive disorder based on multi-omics analysis. J Affect Disord. 2024;344:563–76. [DOI] [PubMed]

87.

Jiang Y, Qu Y, Shi L, Ou M, Du Z, Zhou Z, et al. The role of gut microbiota and metabolomic pathways in modulating the efficacy of SSRIs for major depressive disorder. Transl Psychiatry. 2024;14:493. [DOI] [PubMed] [PMC]

88.

Zhao M, Ren Z, Zhao A, Tang Y, Kuang J, Li M, et al. Gut bacteria-driven homovanillic acid alleviates depression by modulating synaptic integrity. Cell Metab. 2024;36:1000–12.e6. [DOI] [PubMed]

89.

Zhang X, Li Y, Guo Y, Sun J, Yang Y. Clinical efficacy of fecal microbiota transplantation in alleviating depressive symptoms: a meta-analysis of randomized trials. Front Psychiatry. 2025;16:1656969. [DOI] [PubMed] [PMC]

90.

Faria R, Paul M, Biswas S, Vivès E, Boisguérin P, Sousa Â, et al. Peptides vs. Polymers: Searching for the Most Efficient Delivery System for Mitochondrial Gene Therapy. Pharmaceutics. 2022;14:757. [DOI]

91.

Ramos-Jiménez A, Rubio-Valles M, Ramos-Hernández JA, González-Rodríguez E, Moreno-Brito V. Adaptations in Mitochondrial Function Induced by Exercise: A Therapeutic Route for Treatment-Resistant Depression. Int J Mol Sci. 2025;26:8697. [DOI] [PubMed] [PMC]

92.

Chudzik A, Słowik T, Kochalska K, Pankowska A, Łazorczyk A, Andres-Mach M, et al. Continuous Ingestion of Lacticaseibacillus rhamnosus JB-1 during Chronic Stress Ensures Neurometabolic and Behavioural Stability in Rats. Int J Mol Sci. 2022;23:5173. [DOI] [PubMed] [PMC]

93.

Gao Y, Guo L, Wang F, Wang Y, Li P, Zhang D. Development of mitochondrial gene-editing strategies and their potential applications in mitochondrial hereditary diseases: a review. Cytotherapy. 2024;26:11–24. [DOI] [PubMed]