Volume 2, Issue 1 (1-2024)                   Neuroscience Updates 2024, 2(1): 108-121 | Back to browse issues page

XML Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Soliman Wadan A, El-Gemaie D S, Abdelsattar Ahmed M. Emerging Insights into Gut-Brain Axis Dysregulation in Neurodegenerative Disorders. Neuroscience Updates 2024; 2 (1) :108-121
URL: http://neuroupdates.de/article-1-116-en.html
Emerging Insights into Gut-Brain Axis Dysregulation in Neurodegenerative Disorders
Al-Hassan Soliman Wadan *1 , Dana Saeed El-Gemaie2 , Mohamed Abdelsattar Ahmed3
1- Department of Oral Biology, Faculty of Dentistry, Galala University, Suez, Egypt
2- Department of Endodontics, Faculty of Dentistry, Galala University, Suez, Egypt
3- Faculty of Dentistry, Sinai University, Kantara Branch, Ismailia, Egypt
Abstract:   (6435 Views)
This review explores the emerging insights into the gut-brain axis (GBA) and its dysregulation in neurodegenerative disorders such as Alzheimer's, Parkinson's, and Huntington's. The GBA represents a complex communication network linking the intestinal microbiome with the central nervous system (CNS), facilitated by neuro-immuno-endocrine mediators. Such interactions profoundly influence brain health, cognitive functions, and various systemic diseases. Dysbiosis of gut microbiota may be implicated in the pathogenesis of neurodegenerative conditions through mechanisms involving inflammation, metabolic regulation, and neurotransmitter activity. Additionally, dietary habits, lifestyle choices, and environmental factors significantly affect individual gut microbiota profiles, further shaping neurological health. The review highlights the potential of microbiome-based therapies as innovative intervention strategies, emphasizing the metabolic contribution of gut bacteria, such as short-chain fatty acids (SCFAs), to brain function and mood regulation. Understanding these intricate relationships paves the way for novel therapeutic targets to ameliorate neurodegenerative symptoms and enhance overall brain health.
 
Keywords: Gut-Brain Axis, Alzheimer's, Huntington's, Parkinson's
Full-Text [PDF 1185 kb]   (2488 Downloads)    
Type of Study: Review Article | Subject: Neurodegenerative Disease
Received: 2024/10/20 | Accepted: 2024/12/5 | Published: 2024/12/15
References
1. O'Mahony S., Clarke G., Borre Y., Dinan T., Cryan J. (2015). Serotonin, tryptophan metabolism, and the brain-gut-microbiome axis. Behav Brain Res. 277 32-48. [DOI:10.1016/j.bbr.2014.07.027] [PMID] [PMCID]
2. Han W., Tellez L., Perkins M., Perez I., Qu T., Ferreira J., et al. (2018). A neural circuit for gut-induced reward. Cell 175:665-678.e23. [DOI:10.1016/j.cell.2018.08.049] [PMID] [PMCID]
3. Carabotti M, Scirocco A, Maselli MA, Severi C. The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Ann Gastroenterol. 2015 Apr-Jun;28(2):203-209.
4. Di Meo F., Donato S., Di Pardo A., Maglione V., Filosa S., Crispi S. (2018). New therapeutic drugs from bioactive natural molecules: The role of gut microbiota metabolism in neurodegenerative diseases. Curr. Drug Metab. 19 478-489. [DOI:10.2174/1389200219666180404094147] [PMID]
5. Bonaz B., Bernstein C. (2013). Brain-gut interactions in inflammatory bowel disease. Gastroenterology 144 36-49. [DOI:10.1053/j.gastro.2012.10.003] [PMID] [PMCID]
6. Dugger, B., and Dickson, D. (2017). Pathology of neurodegenerative diseases. Cold Spring Harb. Perspect. Biol. 9, a028035. [DOI:10.1101/cshperspect.a028035] [PMID] [PMCID]
7. Lamptey, R., Chaulagain, B., Trivedi, R., Gothwal, A., Layek, B., and Singh, J. A. (2022). Review of the common neurodegenerative disorders: Current therapeutic approaches and the potential role of nanotherapeutics. Int. J. Mol. Sci. 23:1851. [DOI:10.3390/ijms23031851] [PMID]
8. Gubert C., Kong G., Renoir T., Hannan A. (2020). Exercise, diet, and stress as modulators of gut microbiota: Implications for neurodegenerative diseases. Neurobiol. Dis. 134:104621. [DOI:10.1016/j.nbd.2019.104621] [PMID] [PMCID]
9. Cryan J., O'Riordan K., Cowan C., Sandhu K., Bastiaanssen T., Boehme M., et al. (2019). The microbiota-gut-brain axis. Physiol. Rev. 99 1877-2013. [DOI:10.1152/physrev.00018.2018] [PMID]
10. Manolis, A., Manolis, T., Melita, H., and Manolis, A. (2022). Gut microbiota and cardiovascular disease: Symbiosis versus dysbiosis. Curr. Med. Chem. 29, 4050-4077. [DOI:10.2174/0929867328666211213112949] [PMID]
11. Kurilshikov, A., Wijmenga, C., Fu, J., & Zhernakova, A. (2017). Host genetics and gut microbiome: challenges and perspectives. Trends in immunology, 38(9), 633-647. [DOI:10.1016/j.it.2017.06.003] [PMID]
12. Yatsunenko, T., Rey, F., Manary, M. et al. Human gut microbiome viewed across age and geography. Nature 486, 222-227 (2012). [DOI:10.1038/nature11053] [PMID]
13. Jiang C, Li G, Huang P, Liu Z, Zhao B. The Gut Microbiota and Alzheimer's Disease. J Alzheimers Dis. 2017;58(1):1-15. [DOI:10.3233/JAD-161141] [PMID]
14. Ning, J., Huang, S., Chen, S., Zhang, Y., Huang, Y., and Yu, J. (2022). Investigating casual associations among gut microbiota, metabolites, and neurodegenerative diseases: A Mendelian randomization study. J. Alzheimers Dis. 87, 211-222. [DOI:10.3233/JAD-215411] [PMID]
15. Raval, U., Harary, J., Zeng, E., and Pasinetti, G. (2020). The dichotomous role of the gut microbiome in exacerbating and ameliorating neurodegenerative disorders. Expert Rev. Neur other. 20, 673-686. [DOI:10.1080/14737175.2020.1775585] [PMID] [PMCID]
16. Shoubridge, A., Fourrier, C., Choo, J., Proud, C., Sargeant, T., and Rogers, G. (2021). Gut microbiome regulation of autophagic flux and neurodegenerative disease risks. Front. Microbiol. 12:817433. [DOI:10.3389/fmicb.2021.817433] [PMID] [PMCID]
17. Sarubbo, F., Cavallucci, V., and Pani, G. (2022). The influence of gut microbiota on neurogenesis: Evidence and hopes. Cells 11:382. [DOI:10.3390/cells11030382] [PMID] [PMCID]
18. Chidambaram, S., Essa, M., Rathipriya, A., Bishir, M., Ray, B., Mahalakshmi, A., et al. (2022). Gut dysbiosis, defective autophagy and altered immune responses in neurodegenerative diseases: Tales of a vicious cycle. Pharmacol. Ther. 231:107988. [DOI:10.1016/j.pharmthera.2021.107988] [PMID] [PMCID]
19. Dinan TG, Cryan JF. The Microbiome-Gut-Brain Axis in Health and Disease. Gastroenterol Clin North Am. 2017 Mar;46(1):77-89. [DOI:10.1016/j.gtc.2016.09.007] [PMID]
20. Kaur H, Bose C, Mande SS. Tryptophan Metabolism by Gut Microbiome and Gut-Brain-Axis: An in silico Analysis. Front Neurosci. 2019 Dec 18;13:1365. [DOI:10.3389/fnins.2019.01365] [PMID] [PMCID]
21. Lai, Y., Dhingra, R., Zhang, Z., Ball, L. M., Zylka, M. J., & Lu, K. (2021). Toward elucidating the human gut microbiota-brain Axis: molecules, biochemistry, and implications for health and diseases. Biochemistry, 61(24), 2806-2821. [DOI:10.1021/acs.biochem.1c00656] [PMID] [PMCID]
22. Sun, L. J., Li, J. N., & Nie, Y. Z. (2020). Gut hormones in microbiota-gut-brain cross-talk. Chinese medical journal, 133(7), 826-833. [DOI:10.1097/CM9.0000000000000706] [PMID] [PMCID]
23. Wiefels, M. D., Furar, E., Eshraghi, R. S., Mittal, J., Memis, I., Moosa, M., ... & Eshraghi, A. A. (2024). Targeting gut dysbiosis and microbiome metabolites for the development of therapeutic modalities for neurological disorders. Current neuropharmacology, 22(1), 123-139. [DOI:10.2174/1570159X20666221003085508] [PMID] [PMCID]
24. Colombo, A. V., Sadler, R. K., Llovera, G., Singh, V., Roth, S., Heindl, S., & Liesz, A. (2021). Microbiota-derived short chain fatty acids modulate microglia and promote Aβ plaque deposition. elife, 10, e59826. [DOI:10.7554/eLife.59826.sa2] [PMCID]
25. Haas-Neill, S., & Forsythe, P. (2020). A budding relationship: bacterial extracellular vesicles in the microbiota-gut-brain axis. International journal of molecular sciences, 21(23), 8899. [DOI:10.3390/ijms21238899] [PMID] [PMCID]
26. Tan, L., Yu, J., and Tan, L. (2012). The kynurenine pathway in neurodegenerative diseases: Mechanistic and therapeutic considerations. J. Neurol. Sci. 323, 1-8. [DOI:10.1016/j.jns.2012.08.005] [PMID]
27. Breda, C., Sathyasaikumar, K., Sograte Idrissi, S., Notarangelo, F., Estranero, J., Moore, G., et al. (2016). Tryptophan-2,3-dioxygenase (TDO) inhibition ameliorates neurodegeneration by modulation of kynurenine pathway metabolites. Proc. Natl. Acad. Sci. U.S.A. 113, 5435-5440. [DOI:10.1073/pnas.1604453113] [PMID] [PMCID]
28. Lim, C., Fernández-Gomez, F., Braidy, N., Estrada, C., Costa, C., Costa, S., et al. (2017). Involvement of the kynurenine pathway in the pathogenesis of Parkinson's disease. Prog. Neurobiol. 155, 76-95. [DOI:10.1016/j.pneurobio.2015.12.009] [PMID]
29. Lovelace, M., Varney, B., Sundaram, G., Lennon, M., Lim, C., Jacobs, K., et al. (2017). Recent evidence for an expanded role of the kynurenine pathway of tryptophan metabolism in neurological diseases. Neuropharmacology 112, 373-388. [DOI:10.1016/j.neuropharm.2016.03.024] [PMID] [PMCID]
30. Guillemin, G., Cullen, K., Lim, C., Smythe, G., Garner, B., Kapoor, V., et al. (2007). Characterization of the kynurenine pathway in human neurons. J. Neurosci. 27, 12884-12892. [DOI:10.1523/JNEUROSCI.4101-07.2007] [PMID] [PMCID]
31. Montoro, P., Carbone, V., Quiroz Jde, D., De Simone, F., and Pizza, C. (2004). Identification and quantification of components in extracts of Uncaria tomentosa by HPLC-ES/MS. Phytochem. Anal. 15, 55-64. [DOI:10.1002/pca.740] [PMID]
32. Grasselli, J., Elez, E., Caratù, G., Matito, J., Santos, C., Macarulla, T., et al. (2017). Concordance of blood- and tumor-based detection of RAS mutations to guide anti-EGFR therapy in metastatic colorectal cancer. Ann. Oncol. 28, 1294-1301. [DOI:10.1093/annonc/mdx112] [PMID] [PMCID]
33. Di Giorgio, C., Lamidi, M., Delmas, F., Balansard, G., and Ollivier, E. (2006). Antileishmanial activity of quinovic acid glycosides and cadambine acid isolated from Nauclea diderrichii. Planta Med. 72, 1396-1402. [DOI:10.1055/s-2006-951726] [PMID]
34. Russo, I., Amornphimoltham, P., Weigert, R., Barlati, S., and Bosetti, F. (2011). Cyclooxygenase-1 is involved in the inhibition of hippocampal neurogenesis after lipopolysaccharide-induced neuroinflammation. Cell Cycle 10, 2568-2573. [DOI:10.4161/cc.10.15.15946] [PMID] [PMCID]
35. Kalyan, M., Tousif, A., Sonali, S., Vichitra, C., Sunanda, T., Praveenraj, S., et al. (2022). Role of endogenous lipopolysaccharides in neurological disorders. Cells 11:4038. [DOI:10.3390/cells11244038] [PMID] [PMCID]
36. Winter, G., Hart, R. A., Charlesworth, R. P., & Sharpley, C. F. (2018). Gut microbiome and depression: what we know and what we need to know. Reviews in the Neurosciences, 29(6), 629-643. [DOI:10.1515/revneuro-2017-0072] [PMID]
37. De Caro C, Iannone LF, Citraro R, Striano P, De Sarro G, Constanti A, Cryan JF, Russo E. Can we 'seize' the gut microbiota to treat epilepsy? Neurosci Biobehav Rev. 2019 Dec;107:750-764. [DOI:10.1016/j.neubiorev.2019.10.002] [PMID]
38. Pascale A, Marchesi N, Govoni S, Barbieri A. Targeting the microbiota in pharmacology of psychiatric disorders. Pharmacol Res. 2020 Jul;157:104856. [DOI:10.1016/j.phrs.2020.104856] [PMID]
39. Wang Z, Wang Z, Lu T, Chen W, Yan W, Yuan K, Shi L, Liu X, Zhou X, Shi J, Vitiello MV, Han Y, Lu L. The microbiota-gut-brain axis in sleep disorders. Sleep Med Rev. 2022 Oct;65:101691. [DOI:10.1016/j.smrv.2022.101691] [PMID]
40. Reese, A. T., & Carmody, R. N. (2019). Thinking outside the cereal box: noncarbohydrate routes for dietary manipulation of the gut microbiota. Applied and Environmental Microbiology, 85(10), e02246-18. [DOI:10.1128/AEM.02246-18] [PMID] [PMCID]
41. Alshial, E. E., Abdulghaney, M. I., Wadan, A. S., Abdellatif, M. A., Ramadan, N. E., Suleiman, A. M., Waheed, N., Abdellatif, M., & Mohammed, H. S. (2023). Mitochondrial dysfunction and neurological disorders: A narrative review and treatment overview. Life Sciences, 334, 122257. [DOI:10.1016/j.lfs.2023.122257] [PMID]
42. Mohamed, W., Kumar, J., Alghamdi, B. S., Soliman, A., & Toshihide, Y. (2023). Neurodegeneration and inflammation crosstalk: Therapeutic targets and perspectives. IBRO Neuroscience Reports, 14, 95-110. [DOI:10.1016/j.ibneur.2022.12.003] [PMID] [PMCID]
43. Shandilya, S., Kumar, S., Jha, N. K., Kesari, K. K., & Ruokolainen, J. (2022). Interplay of gut microbiota and oxidative stress: Perspective on neurodegeneration and neuroprotection. Journal of Advanced Research, 38, 223-244. [DOI:10.1016/j.jare.2021.09.005] [PMID] [PMCID]
44. Martin, C. R., Osadchiy, V., Kalani, A., & Mayer, E. A. (2018). The brain-gut-microbiome axis. Cellular and molecular gastroenterology and hepatology, 6(2), 133-148. [DOI:10.1016/j.jcmgh.2018.04.003] [PMID] [PMCID]
45. Tolba, M. M., Jabbar, A., Afzal, S., Mahmoud, M., Zulfiqar, F., El-Soudany, I., … Ellakwa, D. E. S. (2023). A Promising RNA Nanotechnology in Clinical Therapeutics: a Future Perspective Narrative Review. Future Science OA, 9(8). [DOI:10.2144/fsoa-2023-0067] [PMID] [PMCID]
46. Ceppa, F. A., Izzo, L., Sardelli, L., Raimondi, I., Tunesi, M., Albani, D., & Giordano, C. (2020). Human gut-microbiota interaction in neurodegenerative disorders and current engineered tools for its modeling. Frontiers in cellular and infection microbiology, 10, 297. [DOI:10.3389/fcimb.2020.00297] [PMID] [PMCID]
47. Soliman, AH., Mohamed, W. (2023b). Nutrigenomics and Trace Elements: Hopes and Hypes for Parkinson's Treatment. In: Mohamed, W., Sandhir, R. (eds) Trace Elements in Brain Health and Diseases. Nutritional Neurosciences. Springer, Singapore. [DOI:10.1007/978-981-99-1513-2_3] [PMCID]
48. Sayed, Z.S., Khattap, M.G., Madkour, M.A. et al. Circulating tumor cells clusters and their role in Breast cancer metastasis; a review of literature. Discov Onc 15, 94 (2024). [DOI:10.1007/s12672-024-00949-7] [PMID] [PMCID]
49. Cox, L. M., & Weiner, H. L. (2018). Microbiota signaling pathways that influence neurologic disease. Neurotherapeutics, 15(1), 135-145. [DOI:10.1007/s13311-017-0598-8] [PMID] [PMCID]
50. Soliman, A., & Abdellatif, M. (2023a). COVID-19 disease treatment: Pivotal challenges in the arena of umbilical cord-mesenchymal stem cells (UC-MSCs). Frontiers in Cell and Developmental Biology, 11, 1146835. [DOI:10.3389/fcell.2023.1146835] [PMID] [PMCID]
51. Munir, M. U., Ali, S. A., Chung, K. H. K., Kakinen, A., Javed, I., & Davis, T. P. (2024). Reverse engineering the Gut-Brain Axis and microbiome-metabolomics for symbiotic/pathogenic balance in neurodegenerative diseases. Gut Microbes, 16(1), 2422468. [DOI:10.1080/19490976.2024.2422468] [PMID] [PMCID]
52. Sanaeifar, F., Pourranjbar, S., Pourranjbar, M., Ramezani, S., Mehr, S. R., Wadan, A. S., & Khazeifard, F. (2024). Beneficial effects of physical exercise on cognitive-behavioral impairments and brain-derived neurotrophic factor alteration in the limbic system induced by neurodegeneration. Experimental Gerontology, 195, 112539. [DOI:10.1016/j.exger.2024.112539] [PMID]
53. Bravo, J. A., Forsythe, P., Chew, M. V., Escaravage, E., Savignac, H. M., Dinan, T. G., ... & Cryan, J. F. (2011). Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proceedings of the National Academy of Sciences, 108(38), 16050-16055. [DOI:10.1073/pnas.1102999108] [PMID]
54. Sgritta, M., Dooling, S. W., Buffington, S. A., Momin, E. N., Francis, M. B., Britton, R. A., & Costa-Mattioli, M. (2019). Mechanisms underlying microbial-mediated changes in social behavior in mouse models of autism spectrum disorder. Neuron, 101(2), 246-259. [DOI:10.1016/j.neuron.2018.11.018] [PMID]
55. Wadan AS, Raza ML, Moradikor N. Synaptic modulation by coffee compounds: Insights into neural plasticity. Progress in Brain Research. 2024a ;289:181-191. [DOI:10.1016/bs.pbr.2024.06.008] [PMID]
56. Liu, L. S., Winston, J. H., Shenoy, M. M., Song, G. Q., Chen, J. D., & Pasricha, P. J. (2008). A rat model of chronic gastric sensorimotor dysfunction resulting from transient neonatal gastric irritation. Gastroenterology, 134(7), 2070-2079. [DOI:10.1053/j.gastro.2008.02.093] [PMID]
57. Yuan, P. Q., & Taché, Y. (2017). Abdominal surgery induced gastric ileus and activation of M1-like macrophages in the gastric myenteric plexus: prevention by central vagal activation in rats. American Journal of Physiology-Gastrointestinal and Liver Physiology, 313(4), G320-G329. [DOI:10.1152/ajpgi.00121.2017] [PMID] [PMCID]
58. Wang, H., Ni, X., Qing, X., Liu, L., Lai, J., Khalique, A., & Zeng, D. (2017). Probiotic enhanced intestinal immunity in broilers against subclinical necrotic enteritis. Frontiers in immunology, 8, 1592. [DOI:10.3389/fimmu.2017.01592] [PMID] [PMCID]
59. Bonaz B, Sinniger V, Pellissier S. Vagus Nerve Stimulation at the Interface of Brain-Gut Interactions. Cold Spring Harb Perspect Med. 2019 Aug 1;9(8):a034199. [DOI:10.1101/cshperspect.a034199] [PMID] [PMCID]
60. Gribble FM, Reimann F. Enteroendocrine Cells: Chemosensors in the Intestinal Epithelium. Annu Rev Physiol. 2016;78:277-99. [DOI:10.1146/annurev-physiol-021115-105439] [PMID]
61. Travagli RA, Anselmi L. Vagal neurocircuitry and its influence on gastric motility. Nat Rev Gastroenterol Hepatol. 2016 Jul;13(7):389-401. [DOI:10.1038/nrgastro.2016.76] [PMID] [PMCID]
62. Wadan, A. S. (2025). The Revolutionary Biocomputing Technology of Organoid Intelligence (OI) as the Forefront of AI and Medicine. In A. Radwan, S. Abd-El-Hafiz, I. Abdel Halim, Y. Liu, & M. Qiu (Eds.), Interdisciplinary Studies on Digital Transformation and Innovation: Business, Education, and Medical Approaches (pp. 215-234). IGI Global Scientific Publishing. [DOI:10.4018/979-8-3373-1132-6.ch008]
63. Kaelberer MM, Buchanan KL, Klein ME, Barth BB, Montoya MM, Shen X, Bohórquez DV. A gut-brain neural circuit for nutrient sensory transduction. Science. 2018 Sep 21;361(6408):eaat5236. [DOI:10.1126/science.aat5236] [PMID] [PMCID]
64. Tian, P., Wang, G., Zhao, J., Zhang, H., & Chen, W. (2019). Bifidobacterium with the role of 5-hydroxytryptophan synthesis regulation alleviates the symptom of depression and related microbiota dysbiosis. The Journal of nutritional biochemistry, 66, 43-51. [DOI:10.1016/j.jnutbio.2019.01.007] [PMID]
65. Kowalski K, Mulak A. Brain-Gut-Microbiota Axis in Alzheimer's Disease. J Neurogastroenterol Motil. 2019 Jan 31;25(1):48-60. [DOI:10.5056/jnm18087] [PMID]
66. Parker, A., Fonseca, S., & Carding, S. R. (2020). Gut microbes and metabolites as modulators of blood-brain barrier integrity and brain health. Gut microbes, 11(2), 135-157. [DOI:10.1080/19490976.2019.1638722] [PMID] [PMCID]
67. Nagpal, R., & Yadav, H. (2017). Bacterial translocation from the gut to the distant organs: an overview. Annals of Nutrition and Metabolism, 71(Suppl. 1), 11-16. [DOI:10.1159/000479918] [PMID]
68. Tang, W., Zhu, H., Feng, Y., Guo, R., & Wan, D. (2020). The impact of gut microbiota disorders on the blood-brain barrier. Infection and Drug Resistance, 3351-3363. [DOI:10.2147/IDR.S254403] [PMID] [PMCID]
69. Ragab, M., Soliman, A., Shaltout, A. E. R., El-Ramly, T. A., Morris, M., Mohamed, O. A. A., Ibrahim, R., & Dakhlaah, D. (2024). Decoding Parkinson's disease: A multifaceted approach to diagnosis and biomarker discovery. Essential Guide to Neurodegenerative Disorders, 235-256. [DOI:10.1016/B978-0-443-15702-8.00015-4]
70. Siddiq, A., Shrestha, S., Das, M., Chodnekar, S. Y., Wadan, A. S., Ayad, Y. W., & Ashraf, G. M. (2024). Nonpharmacological therapies for neurodegenerative disorders. The Neurodegeneration Revolution, 127-165. [DOI:10.1016/B978-0-443-28822-7.00021-0]
71. Padhi, P., Worth, C., Zenitsky, G., Jin, H., Sambamurti, K., Anantharam, V., ... & Kanthasamy, A. G. (2022). Mechanistic insights into gut microbiome dysbiosis-mediated neuroimmune dysregulation and protein misfolding and clearance in the pathogenesis of chronic neurodegenerative disorders. Frontiers in neuroscience, 16, 836605. [DOI:10.3389/fnins.2022.836605] [PMID] [PMCID]
72. Wadan, A. S., & Mohamed, W. (2024c). Various zebrafish models of Parkinson's disease: What gives us hope. Translational Models of Parkinson' s Disease and Related Movement Disorders, 219-230. [DOI:10.1016/B978-0-443-16128-5.00013-X]
73. Mou, Y., Du, Y., Zhou, L., Yue, J., Hu, X., Liu, Y., & Dong, B. (2022). Gut microbiota interact with the brain through systemic chronic inflammation: implications on neuroinflammation, neurodegeneration, and aging. Frontiers in immunology, 13, 796288. [DOI:10.3389/fimmu.2022.796288] [PMID] [PMCID]
74. Neamah, A.S., Wadan, AH.S., Lafta, F.M. et al. The potential role of targeting the leptin receptor as a treatment for breast cancer in the context of hyperleptinemia: a literature review. Naunyn-Schmiedeberg's Arch Pharmacol (2024). [DOI:10.1007/s00210-024-03592-9] [PMID]
75. Abbass, M. M. S., Rady, D., El Moshy, S., Ahmed Radwan, I., Wadan, A. -H. S., Dörfer, C. E., & El-Sayed, K. M. F. (2024). The Temporomandibular Joint and the Human Body: A New Perspective on Cross Talk. Dentistry Journal, 12(11), 357. [DOI:10.3390/dj12110357] [PMID] [PMCID]
76. Lukiw, W. J. (2020). Gastrointestinal (GI) tract microbiome-derived neurotoxins-potent neuro-inflammatory signals from the GI tract via the systemic circulation into the brain. Frontiers in cellular and infection microbiology, 10, 22. [DOI:10.3389/fcimb.2020.00022] [PMID] [PMCID]
77. 2022 Alzheimer's disease facts and figures. Alzheimers Dement. 2022 Apr;18(4):700-789. [DOI:10.1002/alz.12638] [PMID]
78. Spitzer, M. H., & Nolan, G. P. (2016). Mass cytometry: single cells, many features. Cell, 165(4), 780-791. [DOI:10.1016/j.cell.2016.04.019] [PMID]
79. Bhattacharjee, S., & Lukiw, W. J. (2013). Alzheimer's disease and the microbiome. Frontiers in cellular neuroscience, 7, 153. [DOI:10.3389/fncel.2013.00153] [PMID] [PMCID]
80. Ali, L. S., Attia, Y. A. M., Mourad, S., Halawa, E. M., Abd Elghaffar, N. H., Shokry, S., … Elekhnawy, E. (2024). The missing link between cancer stem cells and immunotherapy. Current Medical Research and Opinion, 40(11), 1963-1984. [DOI:10.1080/03007995.2024.2407963] [PMID]
81. Madkour, M. A., Altaf, R. A., Sayed, Z. S., Yasen, N. S., Elbary, H. A., Elsayed, R. A., Mohamed, E. N., Toema, M., Wadan, H. S., Nafady, M. H., & El-Benhawy, S. A. (2023). The Role of Gut Microbiota in Modulating Cancer Therapy Efficacy. Advanced Gut & Microbiome Research, 2024(1), 9919868. [DOI:10.1155/2024/9919868]
82. Ho, N. T., Li, F., Lee-Sarwar, K. A., Tun, H. M., Brown, B. P., Pannaraj, P. S., & Kuhn, L. (2018). Meta-analysis of effects of exclusive breastfeeding on infant gut microbiota across populations. Nature communications, 9(1), 4169. [DOI:10.1038/s41467-018-06473-x] [PMID] [PMCID]
83. Kincaid, I. A. (2021). Lying to myself that I feel just fine makes my gut sick: gastrointestinal symptoms explained by experiental avoidance. Medica Jadertina, 51(3), 227-242.
84. Vogt, N. M., Romano, K. A., Darst, B. F., Engelman, C. D., Johnson, S. C., Carlsson, C. M., & Rey, F. E. (2018). The gut microbiota-derived metabolite trimethylamine N-oxide is elevated in Alzheimer's disease. Alzheimer's research & therapy, 10, 1-8. [DOI:10.1186/s13195-018-0451-2] [PMID] [PMCID]
85. Harach, T., Jammes, F., Muller, C., Duthilleul, N., Cheatham, V., Zufferey, V., & Bolmont, T. (2017). Administrations of human adult ischemia-tolerant mesenchymal stem cells and factors reduce amyloid beta pathology in a mouse model of Alzheimer's disease. Neurobiology of aging, 51, 83-96. [DOI:10.1016/j.neurobiolaging.2016.11.009] [PMID]
86. Minter, M. R., Taylor, J. M., & Crack, P. J. (2016). The contribution of neuroinflammation to amyloid toxicity in Alzheimer's disease. Journal of neurochemistry, 136(3), 457-474. [DOI:10.1111/jnc.13411] [PMID]
87. Zhang, L., Wang, Y., Xiayu, X., Shi, C., Chen, W., Song, N., & Qin, C. (2017). Altered gut microbiota in a mouse model of Alzheimer's disease. Journal of Alzheimer's disease, 60(4), 1241-1257. [DOI:10.3233/JAD-170020] [PMID]
88. Cai, Z., Hussain, M. D., & Yan, L. J. (2014). Microglia, neuroinflammation, and beta-amyloid protein in Alzheimer's disease. International Journal of Neuroscience, 124(5), 307-321. [DOI:10.3109/00207454.2013.833510] [PMID]
89. Ma, Q., Xing, C., Long, W., Wang, H. Y., Liu, Q., & Wang, R. F. (2019). Impact of microbiota on central nervous system and neurological diseases: the gut-brain axis. Journal of neuroinflammation, 16, 1-14. [DOI:10.1186/s12974-019-1434-3] [PMID]
90. Schneider, S. A., & Alcalay, R. N. (2017). Neuropathology of genetic synucleinopathies with parkinsonism: review of the literature. Movement Disorders, 32(11), 1504-1523. [DOI:10.1002/mds.27193] [PMID] [PMCID]
91. Lebouvier, T., Neunlist, M., Bruley des Varannes, S., Coron, E., Drouard, A., N'Guyen, J. M., & Derkinderen, P. (2010). Colonic biopsies to assess the neuropathology of Parkinson's disease and its relationship with symptoms. PloS one, 5(9), e12728. [DOI:10.1371/journal.pone.0012728] [PMID] [PMCID]
92. Sampson, T. R., Debelius, J. W., Thron, T., Janssen, S., Shastri, G. G., Ilhan, Z. E., & Mazmanian, S. K. (2016). Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson's disease. Cell, 167(6), 1469-1480. [DOI:10.1016/j.cell.2016.11.018] [PMID]
93. Qian, Y., Yang, X., Xu, S., Huang, P., Li, B., Du, J., & Xiao, Q. (2020). Gut metagenomics-derived genes as potential biomarkers of Parkinson's disease. Brain, 143(8), 2474-2489. [DOI:10.1093/brain/awaa201] [PMID]
94. Romano, S., Savva, G. M., Bedarf, J. R., Charles, I. G., Hildebrand, F., & Narbad, A. (2021). Meta-analysis of the Parkinson's disease gut microbiome suggests alterations linked to intestinal inflammation. npj Parkinson's Disease, 7(1), 27. [DOI:10.1038/s41531-021-00156-z] [PMID] [PMCID]
95. Geirnaert, A., Steyaert, A., Eeckhaut, V., Debruyne, B., Arends, J. B., Van Immerseel, F., & Van de Wiele, T. (2014). Butyricicoccus pullicaecorum, a butyrate producer with probiotic potential, is intrinsically tolerant to stomach and small intestine conditions. Anaerobe, 30, 70-74. [DOI:10.1016/j.anaerobe.2014.08.010] [PMID]
96. Vacca, M., Celano, G., Calabrese, F. M., Portincasa, P., Gobbetti, M., & De Angelis, M. (2020). The controversial role of human gut lachnospiraceae. Microorganisms, 8(4), 573. [DOI:10.3390/microorganisms8040573] [PMID]
97. Desai, M. S., Seekatz, A. M., Koropatkin, N. M., Kamada, N., Hickey, C. A., Wolter, M., & Martens, E. C. (2016). A dietary fiber-deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility. Cell, 167(5), 1339-1353. [DOI:10.1016/j.cell.2016.10.043] [PMID]
Send email to the article author

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

© 2026 CC BY-NC 4.0 | Neuroscience Updates