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Gut Microbiota Regulates Epigenetic Remodelling in the Amygdala: A Role in Repeated Mild Traumatic Brain Injury (rMTBI)-Induced Anxiety

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Abstract

Gut microbiota serves in the development and maintenance of phenotype. However, the underlying mechanisms are still in its infancy. The current study shows epigenetic remodelling in the brain as a causal mechanism in the gut microbiota-brain axis. Like in trauma patients, gut dysbiosis and anxiety were comorbid in adult male Wistar rats subjected to repeated mild traumatic brain injuries (rMTBI). rMTBI caused epigenetic dysregulation of brain-derived neurotrophic factor (Bdnf) expression in the amygdala, owing to the formation of transcriptional co-repressor complex due to dynamic interaction between histone deacetylase and DNA methylation modification at the Bdnf gene promoter. The probiosis after faecal microbiota transplantation (FMT) from healthy naïve rats or by administration of single strain probiotic (SSP), Lactobacillus rhamnosus GG (LGG), recuperated rMTBI-induced anxiety. Concurrently, LGG infusion or naïve FMT also dislodged rMTBI-induced co-repressor complex resulting in the normalization of Bdnf expression and neuronal plasticity as measured by Golgi-Cox staining. Furthermore, sodium butyrate, a short-chain fatty acid, produced neurobehavioural effects similar to naïve FMT or LGG administration. Interestingly, the gut microbiota from rMTBI-exposed rats per se was able to provoke anxiety in naïve rats in parallel with BDNF deficits. Therefore, gut microbiota seems to be causally linked with the chromatin remodelling necessary for neuroadaptations via neuronal plasticity which drives experience-dependent behavioural manifestations.

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Data Availability

The datasets used during the present study are available on reasonable request.

Abbreviations

ASD:

Autism spectrum disorder

BDNF:

Brain-derived neurotrophic factor

BLA:

Basolateral amygdala

CeA:

Central amygdala

FMT:

Faecal microbiota transplantation

HDAC:

Histone deacetylase

LDB:

Light dark box exploration test

LGG:

Lactobacillus rhamnosus GG

MeCP2:

Methyl CpG binding protein 2

OFT:

Open field test

PTSD:

Post-traumatic stress disorder

rMTBI:

Repeated mild traumatic brain injury

SB:

Sodium butyrate

SCFA:

Short-chain fatty acid

SSP:

Single strain probiotic

References

  1. Sudo N, Chida Y, Aiba Y et al (2004) Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J Physiol 558:263–275. https://doi.org/10.1113/jphysiol.2004.063388

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Cryan JF, Dinan TG (2012) Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci 13:701–712. https://doi.org/10.1038/nrn3346

    Article  CAS  PubMed  Google Scholar 

  3. Cryan JF, O’Riordan KJ, Sandhu K et al (2020) The gut microbiome in neurological disorders. Lancet Neurol 19:179–194. https://doi.org/10.1016/S1474-4422(19)30356-4

    Article  CAS  PubMed  Google Scholar 

  4. Simpson CA, Diaz-Arteche C, Eliby D et al (2021) The gut microbiota in anxiety and depression – a systematic review. Clin Psychol Rev 83:101943. https://doi.org/10.1016/j.cpr.2020.101943

    Article  PubMed  Google Scholar 

  5. Heijtz RD, Wang S, Anuar F et al (2011) Normal gut microbiota modulates brain development and behavior. Proc Natl Acad Sci U S A 108:3047–3052. https://doi.org/10.1073/pnas.1010529108

    Article  PubMed Central  Google Scholar 

  6. Sharon G, Cruz NJ, Kang DW et al (2019) Human gut microbiota from autism spectrum disorder promote behavioral symptoms in mice. Cell 177:1600-1618.e17. https://doi.org/10.1016/j.cell.2019.05.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Galland L (2014) The gut microbiome and the brain. J Med Food 17:1261–1272. https://doi.org/10.1089/jmf.2014.7000

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Marrocco F, Delli Carpini M, Garofalo S et al (2022) Short-chain fatty acids promote the effect of environmental signals on the gut microbiome and metabolome in mice. Commun Biol 5:1–13. https://doi.org/10.1038/s42003-022-03468-9

    Article  CAS  Google Scholar 

  9. Needham BD, Funabashi M, Adame MD et al (2022) A gut-derived metabolite alters brain activity and anxiety behaviour in mice. Nature 602:647–653. https://doi.org/10.1038/s41586-022-04396-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Spichak S, Donoso F, Moloney GM et al (2021) Microbially-derived short-chain fatty acids impact astrocyte gene expression in a sex-specific manner. Brain Behav Immun - Heal 16:100318. https://doi.org/10.1016/j.bbih.2021.100318

    Article  CAS  Google Scholar 

  11. Mews P, Calipari ES, Day J et al (2021) From circuits to chromatin: the emerging role of epigenetics in mental health. J Neurosci 41:873–882. https://doi.org/10.1523/JNEUROSCI.1649-20.2020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Delgado-Morales R, Agís-Balboa RC, Esteller M, Berdasco M (2017) Epigenetic mechanisms during ageing and neurogenesis as novel therapeutic avenues in human brain disorders. Clin Epigenetics 9:1–18. https://doi.org/10.1186/s13148-017-0365-z

    Article  CAS  Google Scholar 

  13. Mansuy IM, Mohanna S (2011) Epigenetics and the human brain: where nurture meets nature. Cerebrum 2011:1–8

  14. Jaworska J, Zalewska T, Sypecka J, Ziemka-Nalecz M (2019) Effect of the HDAC inhibitor, sodium butyrate, on neurogenesis in a rat model of neonatal hypoxia–ischemia: potential mechanism of action. Mol Neurobiol 56:6341–6370. https://doi.org/10.1007/s12035-019-1518-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Stilling RM, Dinan TG, Cryan JF (2014) Microbial genes, brain & behaviour - epigenetic regulation of the gut-brain axis. Genes, Brain Behav 13:69–86. https://doi.org/10.1111/gbb.12109

    Article  CAS  PubMed  Google Scholar 

  16. Woo V, Alenghat T (2022) Epigenetic regulation by gut microbiota. Gut Microbes 14. https://doi.org/10.1080/19490976.2021.2022407

  17. Moonat S, Sakharkar AJ, Zhang H et al (2013) Aberrant histone deacetylase2-mediated histone modifications and synaptic plasticity in the amygdala predisposes to anxiety and alcoholism. Biol Psychiatry 73:763–773. https://doi.org/10.1016/j.biopsych.2013.01.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Sun H, Zhang X, Kong Y et al (2021) Maternal separation-induced histone acetylation correlates with BDNF-programmed synaptic changes in an animal model of PTSD with sex differences. Mol Neurobiol 58:1738–1754. https://doi.org/10.1007/s12035-020-02224-6

    Article  CAS  PubMed  Google Scholar 

  19. Pandey SC, Zhang H, Roy A, Misra K (2006) Central and medial amygdaloid brain-derived neurotrophic factor signaling plays a critical role in alcohol-drinking and anxiety-like behaviors. J Neurosci 26:8320–8331. https://doi.org/10.1523/JNEUROSCI.4988-05.2006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Moonat S, Sakharkar AJ, Zhang H, Pandey SC (2011) The role of amygdaloid brain-derived neurotrophic factor, activity-regulated cytoskeleton-associated protein and dendritic spines in anxiety and alcoholism. Addict Biol 16:238–250. https://doi.org/10.1111/j.1369-1600.2010.00275.x

    Article  CAS  PubMed  Google Scholar 

  21. Sagarkar S, Bhamburkar T, Shelkar G et al (2017) Minimal traumatic brain injury causes persistent changes in DNA methylation at BDNF gene promoters in rat amygdala: a possible role in anxiety-like behaviors. Neurobiol Dis 106:101–109. https://doi.org/10.1016/j.nbd.2017.06.016

    Article  CAS  PubMed  Google Scholar 

  22. Peng L, Liu X, Yang Y et al (2021) Histone deacetylase 2-mediated epigenetic regulation is involved in the early isoflurane exposure-related increase in susceptibility to anxiety-like behaviour evoked by chronic variable stress in mice. Neurochem Res 46:2333–2347. https://doi.org/10.1007/s11064-021-03368-0

    Article  CAS  PubMed  Google Scholar 

  23. Sada N, Fujita Y, Mizuta N et al (2020) Inhibition of HDAC increases BDNF expression and promotes neuronal rewiring and functional recovery after brain injury. Cell Death Dis 11. https://doi.org/10.1038/s41419-020-02897-w

  24. Urban RJ, Pyles RB, Stewart CJ et al (2020) Altered fecal microbiome years after traumatic brain injury. J Neurotrauma 37:1037–1051. https://doi.org/10.1089/neu.2019.6688

    Article  PubMed  Google Scholar 

  25. Sagarkar S, Balasubramanian N, Mishra S et al (2019) Repeated mild traumatic brain injury causes persistent changes in histone deacetylase function in hippocampus: implications in learning and memory deficits in rats. Brain Res 1711:183–192. https://doi.org/10.1016/j.brainres.2019.01.022

    Article  CAS  PubMed  Google Scholar 

  26. Balasubramanian N, Sagarkar S, Jadhav M et al (2021) Role for histone deacetylation in traumatic brain injury-induced deficits in neuropeptide y in arcuate nucleus: possible implications in feeding behavior. Neuroendocrinology 111:1187–1200. https://doi.org/10.1159/000513638

    Article  CAS  PubMed  Google Scholar 

  27. Sagarkar S, Mahajan S, Choudhary AG et al (2017) Traumatic stress-induced persistent changes in DNA methylation regulate neuropeptide Y expression in rat jejunum. Neurogastroenterol Motil 29:1–11. https://doi.org/10.1111/nmo.13074

    Article  CAS  Google Scholar 

  28. Matharu D, Dhotre D, Balasubramanian N et al (2019) Repeated mild traumatic brain injury affects microbial diversity in rat jejunum. J Biosci 44. https://doi.org/10.1007/s12038-019-9940-0

  29. Balasubramanian N, Sagarkar S, Choudhary AG et al (2021) Epigenetic blockade of hippocampal SOD2 via DNMT3b-mediated DNA methylation: implications in mild traumatic brain injury-induced persistent oxidative damage. Mol Neurobiol 58:1162–1184. https://doi.org/10.1007/s12035-020-02166-z

    Article  CAS  PubMed  Google Scholar 

  30. Du D, Tang W, Zhou C et al (2021) Fecal microbiota transplantation is a promising method to restore gut microbiota dysbiosis and relieve neurological deficits after traumatic brain injury. Oxid Med Cell Longev. https://doi.org/10.1155/2021/5816837

  31. Lin R, Sun Y, Mu P et al (2020) Lactobacillus rhamnosus GG supplementation modulates the gut microbiota to promote butyrate production, protecting against deoxynivalenol exposure in nude mice. Biochem Pharmacol 175:113868. https://doi.org/10.1016/j.bcp.2020.113868

    Article  CAS  PubMed  Google Scholar 

  32. Thananimit S, Pahumunto N, Teanpaisan R (2022) Characterization of short chain fatty acids produced by selected potential probiotic Lactobacillus strains. Biomolecules 12:1–17. https://doi.org/10.3390/biom12121829

    Article  CAS  Google Scholar 

  33. Van den Abbeele P, Goggans M, Deyaert S et al (2023) Lacticaseibacillus rhamnosus ATCC 53103 and Limosilactobacillus reuteri ATCC 53608 synergistically boost butyrate levels upon tributyrin administration ex vivo. Int J Mol Sci 24. https://doi.org/10.3390/ijms24065859

  34. Rebolledo-Solleiro D, Roldán-Roldán G, Díaz D et al (2017) Increased anxiety-like behavior is associated with the metabolic syndrome in non-stressed rats. PLoS ONE 12:1–21. https://doi.org/10.1371/journal.pone.0176554

    Article  CAS  Google Scholar 

  35. Sagarkar S, Choudhary AG, Balasubramanian N et al (2021) LSD1-BDNF activity in lateral hypothalamus-medial forebrain bundle area is essential for reward seeking behavior. Prog Neurobiol 202:102048. https://doi.org/10.1016/j.pneurobio.2021.102048

    Article  CAS  PubMed  Google Scholar 

  36. Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative CT method. Nat Protoc 3:1101–1108. https://doi.org/10.1038/nprot.2008.73

    Article  CAS  PubMed  Google Scholar 

  37. Balasubramanian N, Jadhav G, Sakharkar AJ (2021) Repeated mild traumatic brain injuries perturb the mitochondrial biogenesis via DNA methylation in the hippocampus of rat. Mitochondrion 61:11–24. https://doi.org/10.1016/j.mito.2021.09.001

    Article  CAS  PubMed  Google Scholar 

  38. Zaqout S, Kaindl AM (2016) Golgi-cox staining step by step. Front Neuroanat 10:1–7. https://doi.org/10.3389/fnana.2016.00038

    Article  Google Scholar 

  39. Awathale SN, Waghade AM, Kawade HM et al (2022) Neuroplastic changes in the superior colliculus and hippocampus in self-rewarding paradigm: importance of visual cues. Mol Neurobiol 59:890–915. https://doi.org/10.1007/s12035-021-02597-2

    Article  CAS  PubMed  Google Scholar 

  40. Sagarkar S, Bhat N, Sapre M et al (2022) TET1-induced DNA demethylation in dentate gyrus is important for reward conditioning and reinforcement. Mol Neurobiol 59:5426–5442. https://doi.org/10.1007/s12035-022-02917-0

    Article  CAS  PubMed  Google Scholar 

  41. Ramkumar K, Srikumar BN, Venkatasubramanian D et al (2012) Reversal of stress-induced dendritic atrophy in the prefrontal cortex by intracranial self-stimulation. J Neural Transm 119:533–543. https://doi.org/10.1007/s00702-011-0740-4

    Article  CAS  PubMed  Google Scholar 

  42. SHOLL DA, (1953) Dendritic organization in the neurons of the visual and motor cortices of the cat. J Anat 87:387–406

    PubMed  Google Scholar 

  43. Acosta-peña E, Camacho-Abrego I, Melgarejo-Gutiérrez M et al (2015) Sleep deprivation induces differential morphological changes in the hippocampus and prefrontal cortex in young and old rats. Synapse 69:15–25. https://doi.org/10.1002/syn.21779

    Article  CAS  PubMed  Google Scholar 

  44. Sundman MH, Chen NK, Subbian V, Chou Y, hui, (2017) The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease. Brain Behav Immun 66:31–44. https://doi.org/10.1016/j.bbi.2017.05.009

    Article  CAS  PubMed  Google Scholar 

  45. Hanscom M, Loane DJ, Shea-Donohue T (2021) Brain-gut axis dysfunction in the pathogenesis of traumatic brain injury. J Clin Investig 131:12. https://doi.org/10.1172/JCI143777

    Article  Google Scholar 

  46. Chinna Meyyappan A, Forth E, Wallace CJK, Milev R (2020) Effect of fecal microbiota transplant on symptoms of psychiatric disorders: a systematic review. BMC Psychiatry 20:1–19. https://doi.org/10.1186/s12888-020-02654-5

    Article  Google Scholar 

  47. Yong SJ, Tong T, Chew J, Lim WL (2020) Antidepressive mechanisms of probiotics and their therapeutic potential. Front Neurosci 1. https://doi.org/10.3389/fnins.2019.01361

  48. Liu B, He Y, Wang M et al (2018) Efficacy of probiotics on anxiety—a meta-analysis of randomized controlled trials. Depress Anxiety 35:935–945. https://doi.org/10.1002/da.22811

    Article  PubMed  Google Scholar 

  49. Pinto-Sanchez MI, Hall GB, Ghajar K et al (2017) Probiotic Bifidobacterium longum NCC3001 reduces depression scores and alters brain activity: a pilot study in patients with irritable bowel syndrome. Gastroenterology 153:448-459.e8. https://doi.org/10.1053/j.gastro.2017.05.003

    Article  PubMed  Google Scholar 

  50. Li H, Sun J, Du J et al (2018) Clostridium butyricum exerts a neuroprotective effect in a mouse model of traumatic brain injury via the gut-brain axis. Neurogastroenterol Motil 30:1–12. https://doi.org/10.1111/nmo.13260

    Article  CAS  Google Scholar 

  51. Chen R, Xu Y, Wu P et al (2019) Transplantation of fecal microbiota rich in short chain fatty acids and butyric acid treat cerebral ischemic stroke by regulating gut microbiota. Pharmacol Res 148:104403. https://doi.org/10.1016/j.phrs.2019.104403

    Article  CAS  PubMed  Google Scholar 

  52. Tian P, O’Riordan KJ, Lee YK et al (2020) Towards a psychobiotic therapy for depression: Bifidobacterium breve CCFM1025 reverses chronic stress-induced depressive symptoms and gut microbial abnormalities in mice. Neurobiol Stress 12:100216. https://doi.org/10.1016/j.ynstr.2020.100216

    Article  PubMed  PubMed Central  Google Scholar 

  53. Stenman LK, Patterson E, Meunier J et al (2020) Strain specific stress-modulating effects of candidate probiotics: a systematic screening in a mouse model of chronic restraint stress. Behav Brain Res 379. https://doi.org/10.1016/j.bbr.2019.112376

  54. Patterson E, Ryan PM, Wiley N et al (2019) Gamma-aminobutyric acid-producing lactobacilli positively affect metabolism and depressive-like behaviour in a mouse model of metabolic syndrome. Sci Rep 9:1–15. https://doi.org/10.1038/s41598-019-51781-x

    Article  CAS  Google Scholar 

  55. Bin WY, Melas PA, Wegener G et al (2015) Antidepressant-like effect of sodium butyrate is associated with an increase in tet1 and in 5-hydroxymethylation levels in the BDNF gene. Int J Neuropsychopharmacol 18:1–10. https://doi.org/10.1093/ijnp/pyu032

    Article  CAS  Google Scholar 

  56. Li N, Wang Q, Wang Y et al (2019) Fecal microbiota transplantation from chronic unpredictable mild stress mice donors affects anxiety-like and depression-like behavior in recipient mice via the gut microbiota-inflammation-brain axis. Stress 22:592–602. https://doi.org/10.1080/10253890.2019.1617267

    Article  CAS  PubMed  Google Scholar 

  57. Cholewa-Waclaw J, Bird A, von Schimmelmann M et al (2016) The role of epigenetic mechanisms in the regulation of gene expression in the nervous system. J Neurosci 36:11427–11434. https://doi.org/10.1523/JNEUROSCI.2492-16.2016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Broide RS, Redwine JM, Aftahi N et al (2007) Distribution of histone deacetylases 1–11 in the rat brain. J Mol Neurosci 31:47–58. https://doi.org/10.1007/BF02686117

    Article  CAS  PubMed  Google Scholar 

  59. Persaud NS, Cates HM (2022) The epigenetics of anxiety pathophysiology: a DNA methylation and histone modification focused review. Eneuro 10:0109–21.2021. https://doi.org/10.1523/eneuro.0109-21.2021

  60. Miro-Blanch J, Yanes O (2019) Epigenetic regulation at the interplay between gut microbiota and host metabolism. Front Genet 10:1–9. https://doi.org/10.3389/fgene.2019.00638

    Article  CAS  Google Scholar 

  61. McVey Neufeld KA, O’Mahony SM, Hoban AE et al (2019) Neurobehavioural effects of Lactobacillus rhamnosus GG alone and in combination with prebiotics polydextrose and galactooligosaccharide in male rats exposed to early-life stress. Nutr Neurosci 22:425–434. https://doi.org/10.1080/1028415X.2017.1397875

    Article  CAS  PubMed  Google Scholar 

  62. Collins SM, Kassam Z, Bercik P (2013) The adoptive transfer of behavioral phenotype via the intestinal microbiota: experimental evidence and clinical implications. Curr Opin Microbiol 16:240–245. https://doi.org/10.1016/j.mib.2013.06.004

    Article  PubMed  Google Scholar 

  63. Kelly JR, Borre Y, O’Brien C et al (2016) Transferring the blues: depression-associated gut microbiota induces neurobehavioural changes in the rat. J Psychiatr Res 82:109–118. https://doi.org/10.1016/j.jpsychires.2016.07.019

    Article  PubMed  Google Scholar 

  64. Yan ZX, Gao XJ, Li T et al (2018) Fecal microbiota transplantation in experimental ulcerative colitis reveals associated gut microbial and host metabolic reprogramming. Appl Environ Microbiol 84:1–11. https://doi.org/10.1128/AEM.00434-18

    Article  Google Scholar 

  65. Liang S, Wang T, Hu X et al (2015) Administration of Lactobacillus helveticus NS8 improves behavioral, cognitive, and biochemical aberrations caused by chronic restraint stress. Neuroscience 310:561–577. https://doi.org/10.1016/j.neuroscience.2015.09.033

    Article  CAS  PubMed  Google Scholar 

  66. Liu J, Sun J, Wang F et al (2015) Neuroprotective effects of Clostridium butyricum against vascular dementia in mice via metabolic butyrate. BioMed Res Int. https://doi.org/10.1155/2015/412946

    Article  PubMed  PubMed Central  Google Scholar 

  67. Wei CL, Wang S, Yen JT et al (2019) Antidepressant-like activities of live and heat-killed Lactobacillus paracasei PS23 in chronic corticosterone-treated mice and possible mechanisms. Brain Res 1711:202–213. https://doi.org/10.1016/j.brainres.2019.01.025

    Article  CAS  PubMed  Google Scholar 

  68. Zhou B, Jin G, Pang X et al (2022) Lactobacillus rhamnosus GG colonization in early life regulates gut-brain axis and relieves anxiety-like behavior in adulthood. Pharmacol Res 177. https://doi.org/10.1016/j.phrs.2022.106090

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Acknowledgements

AJS and GJ acknowledge University Grants Commission, Government of India, for the award of UGC-FRP position (UGC-GOI; F.4-5/151-FRP/2014/BSR) and senior research fellowship (File No. JUNE18-356081), respectively. BBD acknowledges the Mahatma Jyotiba Phule Research and Training Institute, Nagpur, for providing junior research fellowship (MAHAJYOTI/Nag./Fellowship/2021-22/1042 (352)) and Indian Council of Medical Research (ICMR) for providing senior research fellowship (2021-15699/F1).

Funding

This work was supported by the grants from the Science and Engineering Research Board (SERB), Government of India (CRG/2020/004971), and Rashtriya Uchchatar Shiksha Abhiyan, GOI (SPPU-RUSA-CBS-TH 4.5) to AJS.

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Authors and Affiliations

  1. Department of Biotechnology, Savitribai Phule Pune University, Pune, 411 007, Maharashtra, India

    Gouri Jadhav & Amul J. Sakharkar

  2. Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur, 440 033, Maharashtra, India

    Biru B. Dudhabhate & Dadasaheb M. Kokare

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  1. Gouri Jadhav
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Contributions

GJ—experimental design, collection and assembly of data, data analysis and interpretation, manuscript writing. BBD—collection and assembly of data, data analysis, manuscript editing. DMK—interpretation, manuscript editing. AJS—overall conception and design of the study, collection and assembly of data, data analysis and interpretation, manuscript writing, funding acquisition, final approval of manuscript, supervision. All the authors contributed and approved the final version of the manuscript.

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Correspondence to Amul J. Sakharkar.

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Animal protocols in the present study were carried out in accordance with the Institutional Animal Ethics Committee (IAEC), Savitribai Phule Pune University, Pune, India (REF.NO.ZOOL/2021/166), and Sinhgad Institute of Pharmacy, Pune, India (Approval No. SIOP/IAEC/2019/01/02).

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Jadhav, G., Dudhabhate, B.B., Kokare, D.M. et al. Gut Microbiota Regulates Epigenetic Remodelling in the Amygdala: A Role in Repeated Mild Traumatic Brain Injury (rMTBI)-Induced Anxiety. Mol Neurobiol (2023). https://doi.org/10.1007/s12035-023-03697-x

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