MicroBio Pharmaceuticals and Pharmacology | Online ISSN 2209-2161
REVIEWS   (Open Access)

Gut Microbiota's Impact on Neurological Health as The Gut-Brain Axis

Shivani Chib 1*, Loiy Elsir Ahmed Hassan 2, Saikat Mukherjee 3

+ Author Affiliations

Microbial Bioactives 7(1) 1-12 https://doi.org/10.25163/microbbioacts.719375

Submitted: 22 November 2023  Revised: 05 January 2024  Published: 17 January 2024 

Abstract

The Gut-Brain Axis (GBA) represents a dynamic and intricate bidirectional communication network that intertwines the gut and the brain. Studies reveal the significant influence of gut microbiota on the central nervous system and neurological health. In order to fully understand the basic connections between gut microbiota and brain health, this review will focus on the underlying processes, possible clinical consequences, and changing field of microbiome-based therapies. The gut microbiota, a diverse range of bacteria, viruses, fungus, and other microbes, is found in the human gut, which functions as a dynamic ecosystem. Despite being mostly recognized for their functions in nutrition metabolism and digestion, these microbes are increasingly important for controlling the central nervous system. Neuroactive substances, such as neurotransmitters and short-chain fatty acids, which are produced in large quantities by the gut microbiota, have a profound impact on behavior, mood, and cognitive performance. Furthermore, the "leaky gut" theory suggests that the immune system and gut microbiota interact, which has implications for a variety of neurological disorders, including neuroinflammatory illnesses. Probiotics, prebiotics, and fecal microbiota transplantation (FMT) have emerged as promising approaches to modify the gut microbiota’s composition and restore homeostasis in a range of neurological conditions. Emerging research suggests that these therapies may be beneficial for a variety of ailments, including anxiety, depression, autism spectrum disorders, and neurodegenerative diseases.Personalized interventions are necessary due to the highly individualised link between gut microbiota and brain health. The precise mechanisms underpinning the influence of gut microbiota on CNS function continue to be an active area of research.

Keywords: Gut-Brain Axis, Microbiota, Neurological Health, Signaling Pathways, Microbiome-based Therapies

References

Abdel-Haq, R., Schlachetzki, J. C. M., Glass, C. K., and Mazmanian, S. K. (2019). Microbiome microglia connections via the gutâ brain axis. J. Exp. Med. 216, 41–59.

Adams, J. B., Johansen, L. J., Powell, L. D., Quig, D., and Rubin, R. A. (2011). Gastrointestinal flora and gastrointestinal status in children with autism comparisons to typical children and correlation with autism severity. BMC Gastroenterol. 11, 1–13.

Aizawa, E., Tsuji, H., Asahara, T., Takahashi, T., Teraishi, T., Yoshida, S., et al. (2016). Possible association of Bifidobacterium and Lactobacillus in the gut microbiota of patients with major depressive disorder. J. Affect. Disord. 202, 254–257.

Akbari E, Asemi Z, Daneshvar Kakhaki R, et al. Effect of probiotic supplementation on cognitive function and metabolic status in Alzheimer's disease: a randomized, double-blind and controlled trial. Front Aging Neurosci. 2016;8:256.

Akbari, E., Asemi, Z., Daneshvar Kakhaki, R., Bahmani, F., Kouchaki, E., Tamtaji, O. R., et al. (2016). Effect of probiotic supplementation on cognitive function and metabolic status in Alzheimer's disease: a randomized, double-blind and controlled trial. Front. Aging Neurosci. 8:256.

Akira, S., and Hemmi, H. (2003). Recognition of pathogen-associated molecular patterns by TLR family. Immunol. Lett. 85, 85–95.

Akkasheh, G., Kashani-Poor, Z., Tajabadi-Ebrahimi, M., Jafari, P., Akbari, H., Taghizadeh, M., et al. (2016). Clinical and metabolic response to probiotic administration in patients with major depressive disorder: a randomized, double-blind, placebo-controlled trial. Nutrition 32, 315–320.

Aktar, R., Parkar, N., Stentz, R., Baumard, L., Parker, A., Goldson, A., et al. (2020). Human resident gut microbe Bacteroides thetaiotaomicron regulates colonic neuronal innervation and neurogenic function. Gut Microbes 11, 1745–1757.

Al Omran, Y., and Aziz, Q. (2014). The brain-gut axis in health and disease. Microbial Endocrinol, 817, 135–153.

Alvarez, E., Martinez, M. D., Roncero, I., Chowen, J. A., Garcia-Cuartero, B., Gispert, J. D., et al. (2005). The expression of GLP1 receptor mRNA and protein allows the effect of GLP-1 on glucose metabolism in the human hypothalamus and brainstem. J. Neurochem. 92, 798–806.

Alzheimer's, A. (2016). Alzheimer's disease facts and figures. Alzheimers Dement. 12, 459–509.

Aresti Sanz, J., and El Aidy, S. (2019). Microbiota and gut neuropeptides: a dual action of antimicrobial activity and neuroimmune response. Psychopharmacology 236, 1597–1609.

Askarova, S., Umbayev, B., Masoud, A. R., Kaiyrlykyzy, A., Safarova, Y., Tsoy, A., et al. (2020). The links between the gut microbiome, aging, modern lifestyle and Alzheimer's disease. Front. Cell. Infect. Microbiol. 10:104.

Atarashi, K., Tanoue, T., Shima, T., Imaoka, A., Kuwahara, T., Momose, Y., et al. (2011). Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331, 337–341.

Baj, A., Moro, E., Bistoletti, M., Orlandi, V., Crema, F., and Giaroni, C. (2019). Glutamatergic signaling along the microbiota-gut-brain axis. Int. J. Mol. Sci. 20:1482.

Barichella, M., Severgnini, M., Cilia, R., Cassani, E., Bolliri, C., Caronni, S., et al. (2019). Unraveling gut microbiota in Parkinson's disease and atypical parkinsonism. Mov. Disord. 34, 396–405.

Bastiaanssen, T. F. S., Cowan, C. S. M., Claesson, M. J., Dinan, T. G., and Cryan, J. F. (2019). Making sense of the microbiome in psychiatry. Int. J. Neuropsychopharmacol. 22, 37–52.

Bäuerl, C., Collado, M. C., Diaz Cuevas, A., Viña, J., and Martínez, G. P. (2018). Shifts in gut microbiota composition in an APP/PSS 1 transgenic mouse model of Alzheimer's disease during lifespan. Lett Appl Microbiol. 66, 464–471.

Bercik, P., Denou, E., Collins, J., Jackson, W., Lu, J., Jury, J., et al. (2011a). The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. Gastroenterology 141:e593, 599–609.e3.

Bercik, P., Park, A. J., Sinclair, D., Khoshdel, A., Lu, J., Huang, X., et al. (2011b). The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gutbrain communication. J Gastrointestinal Motility 23, 1132–1139.

Bercik, P., Verdu, E. F., Foster, J. A., Macri, J., Potter, M., Huang, X., et al. (2010). Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry in mice. Gastroenterology 139:e2101.

Berding, K., and Donovan, S. M. (2016). Microbiome and nutrition in autism spectrum disorder: current knowledge and research needs. Nutr. Rev. 74, 723–736

Berer, K., Gerdes, L. A., Cekanaviciute, E., Jia, X., Xiao, L., Xia, Z., et al. (2017). Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice. PNAS 114, 10719–10724.

Bhargava, P., and Mowry, E. M. (2014). Gut microbiome and multiple sclerosis. Curr. Neurol. Neurosci. Rep. 14, 1–8.

Bhattarai, Y., Si, J., Pu, M., Ross, O. A., McLean, P. J., Till, L., et al. (2021). Role of gut microbiota in regulating gastrointestinal dysfunction and motor symptoms in a mouse model of Parkinson’s disease. Gut Microbes 13:1866974.

Bibbo, S., Dore, M. P., Pes, G. M., Delitala, G., and Delitala, A. P. (2017). Is there a role for gut microbiota in type 1 diabetes pathogenesis? Ann. Med. 49, 11–22.

Blacher, E., Bashiardes, S., Shapiro, H., Rothschild, D., Mor, U., Dori-Bachash, M.,et al. (2019). Potential roles of gut microbiome and metabolites in modulating ALS in mice. Nature 572, 474–480.

Blandini, F., Nappi, G., Tassorelli, C., and Martignoni, E. (2000). Functional changes of the basal ganglia circuitry in Parkinson's disease. Prog. Neurobiol. 62, 63–88.

Blaser, M. J. (2017). The theory of disappearing microbiota and the epidemics of chronic diseases. Nat. Rev. Immunol. 17, 461–463.

Boertien, J. M., Pereira, P. A. B., Aho, V. T. E., and Scheperjans, F. (2019). Increasing comparability and utility of gut microbiome studies in Parkinson 's disease: a systematic review. J. Parkinsons Dis. 9, S297–S312.

Braniste, V., al-Asmakh, M., Kowal, C., Anuar, F., Abbaspour, A., Tóth, M., et al. (2014). The gut microbiota influences blood–brain barrier permeability in mice. Sci. Transl. Med. 6:263ra158.

Bravo, J. A., Forsythe, P., Chew, M. V., Escaravage, E., Savignac, H. M., Dinan, T. G., et al. (2011). Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. PNAS 108, 16050–16055.

Brun, P., Giron, M. C., Qesari, M., Porzionato, A., Caputi, V., Zoppellaro, C., et al. (2013). Toll-like receptor 2 regulates intestinal inflammation by controlling integrity of the enteric nervous system. Gastroenterology 145, 1323–1333.

Bu, X. L., Yao, X. Q., Jiao, S. S., Zeng, F., Liu, Y. H., Xiang, Y., et al. (2015). A study on the association between infectious burden and Alzheimer's disease. Eur. Neurol. 22, 1519–1525

Bui, E., and Fava, M. (2017). From depression to anxiety, and back. Acta Psychiatr. Neurol. Scand. 136, 341–342.

Burberry, A., Wells, M. F., Limone, F., Couto, A., Smith, K. S., Keaney, J., et al. (2020). C9orf72 suppresses systemic and neural inflammation induced by gut bacteria. Nature 582, 89–94.

Capuron, L., and Miller, A. H. (2011). Immune system to brain signaling: neuropsychopharmacological implications. Pharm. Therap. 130, 226–238.

Carabotti, M., Scirocco, A., Maselli, M. A., and Severi, C. (2015). The gut-brain axis:interactions between enteric microbiota, central and enteric nervous systems. Annals Gastroenterol 28:203.

Cekanaviciute E, Yoo BB, Runia TF, et al. Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models. Proc Natl Acad Sci U S A. 2017;114 (40):10713–10718.

Cekanaviciute, E., Yoo, B. B., Runia, T. F., Debelius, J. W., Singh, S., Nelson, C. A., et al. (2017). Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models. PNAS 114, 10713–10718.

Cersosimo, M. G., Raina, G. B., Pecci, C., Pellene, A., Calandra, C. R., Gutiérrez, C.,et al. (2013). Gastrointestinal manifestations in Parkinson’s disease: prevalence and occurrence before motor symptoms. J. Neurol 260, 1332–1338.

Chen, J., Chia, N., Kalari, K. R., Yao, J. Z., Novotna, M., Paz Soldan, M. M., et al. (2016). Multiple sclerosis patients have a distinct gut microbiota compared to healthy controls. Sci. Rep. 6, 1–10.

Chen, Y., Xu, J., and Chen, Y. (2021). Regulation of neurotransmitters by the gut microbiota and effects on cognition in neurological disorders. Nutrients 13:2099.

David LA, Maurice CF, Carmody RN, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505 (7484):559–563.

He Z, Cui BT, Zhang T, et al. Fecal microbiota transplantation cured epilepsy in a case with Crohn's disease: the first report. World J Gastroenterol. 2017;23(19):3565–3568.

Heijtz, R. D., Wang, S., Anuar, F., Qian, Y., Björkholm, B., Samuelsson, A., et al. (2011). Normal gut microbiota modulates brain development and behavior. PNAS 108, 3047–3052.

Heinzel, S., Aho, V. T. E., Suenkel, U., von Thaler, A. K., Schulte, C., and Deuschle, C.(2021). Gut microbiome signatures of risk and prodromal markers of Parkinson disease. Ann. Neurol. 90, E1–E12.

Hill-Burns, E. M., Debelius, J. W., Morton, J. T., Wissemann, W. T., Lewis, M. R., Wallen, Z. D., et al. (2017). Parkinson's disease and Parkinson's disease medications have distinct signatures of the gut microbiome. Mov. Disord. 32, 739–749.

Hirayama, M., and Ohno, K. (2021). Parkinson 's disease and gut microbiota. Ann. Nutr. Metab. 77, 28–35.

Ho, L. K. H., Tong, V. J. W., Syn, N., Nagarajan, N., Tham, E. H., Tay, S. K., et al. (2020). Gut microbiota changes in children with autism spectrum disorder: a systematic review. Gut Pathogens 12, 1–18.

Hsiao, E. Y., McBride, S. W., Hsien, S., Sharon, G., Hyde, E. R., McCue, T., et al. (2013).Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cells 155, 1451–1463.

Hsieh TH, Kuo CW, Hsieh KH, et al. Probiotics alleviate the progressive deterioration of motor functions in a mouse model of Parkinson's disease. Brain Sci. 2020;10(4).

Hu Y, Zhang M, Tian N, et al. The antibiotic clofoctol suppresses glioma stem cell proliferation by activating KLF13. J Clin Invest. 2019;129(8):3072–3085.

Huang, C., Wang, J., Hu, W., Wang, C., Lu, X., Tong, L., et al. (2016). Identification of functional farnesoid X receptors in brain neurons. FEBS Lett. 590, 3233–3242.

Huang, Q., Di, L., Yu, F., Feng, X., Liu, Z., Wei, M., et al. (2022). Alterations in the gut microbiome with hemorrhagic transformation in experimental stroke. CNS Neurosci.Ther. 28, 77–91.

Huang, T. T., Lai, J. B., Du, Y. L., Xu, Y., Ruan, L. M., and Hu, S. H. (2019). Current understanding of gut microbiota in mood disorders: an update of human studies. Front. Genet. 10:98.

Hube, F., Lietz, U., Igel, M., Jensen, P. B., Tornqvist, H., Joost, H. G., et al. (1996). Difference in leptin mRNA levels between omental and subcutaneous abdominal adipose tissue from obese humans. Horm. Metab. Res. 28, 690–693.

Iannone, L. F., Preda, A., Blottière, H. M., Clarke, G., Albani, D., Belcastro, V., et al. (2019). Microbiota-gut brain axis involvement in neuropsychiatric disorders. Expert. Rev. Neurother. 19, 1037–1050.

Kang DW, Adams JB, Gregory AC, et al. Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study. Microbiome. 2017;5(1):10

Lim B, Zimmermann M, Barry NA, Goodman AL. Engineered regulatory systems modulate gene expression of human commensals in the gut. Cell. 2017;169(3):547–558.e15.

 Liu WH, Chuang HL, Huang YT, et al. Alteration of behavior and monoamine levels attributable to Lactobacillus plantarum PS128 in germ-free mice. Behav Brain Res. 2016;298(Pt B):202–209.

Makkawi S, Camara-Lemarroy C, Metz L. Fecal microbiota transplantation associated with 10 years of stability in a patient with SPMS. Neurol Neuroimmunol Neuroinflamm. 2018;5(4):e459.

Peng A, Qiu X, Lai W, et al. Altered composition of the gut microbiome in patients with drug-resistant epilepsy. Epilepsy Res.2018;147:102–107.

Zhan G, Yang N, Li S, et al. Abnormal gut microbiota composition contributes to cognitive dysfunction in SAMP8 mice. Aging. 2018;10(6):1257–1267. (Albany NY).

PDF
Full Text
Export Citation

View Dimensions


View Plumx



View Altmetric



12
Save
0
Citation
430
View
0
Share