Skip to main content

Advertisement

SpringerLink
Log in

Research Hotspots and Frontiers of Alzheimer’s Disease and Gut Microbiota: A Knowledge Mapping and Text Mining Analysis

  • Research
  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Gut microbiota has been confirmed to be closely related to Alzheimer’s disease (AD). Research on gut microbiota and AD has also increased significantly. This study aimed to conduct a bibliometric and visual analysis of published studies related to gut microbiota and AD. Based on the Web of Science Core Collection SCI-Expanded database, we utilize Excel 2019 and visualization analysis tools VOSviewer, Co-Occurrence13.2 (COOC13.2), Citespace, HistCite, and Bibliometrix (R-Tool of R-Studio) for analysis. A total of 1093 related kinds of literature were included, and the number of papers presented an overall increasing trend. The country/region with the most publications is China, the institution is Zhejiang University, the author is Walter J Lukiw from the USA, and the journal is the Journal of Alzheimer’s Disease. Hotspot research areas include the relationship between gut microbiota metabolism and AD, AD treatments related to the gut microbiota, and diseases related to AD and gut microbiota. The future research direction may be T cells, NLRP3 inflammasome, and Porphyromonas gingivalis. Studies on AD and gut microbiota have grown rapidly in recent years. Our research results may provide valuable references for readers and help researchers better find new research directions in the future.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Data Availability

No datasets were generated or analysed during the current study.

References

  1. Kim N, Jeon SH, Ju IG, Gee MS, Do J, Oh MS, Lee JK (2021) Transplantation of gut microbiota derived from Alzheimer’s disease mouse model impairs memory function and neurogenesis in C57BL/6 mice. Brain Behav Immun 98:357–365

    Article  CAS  PubMed  Google Scholar 

  2. Sun J, Xu J, Ling Y, Wang F, Gong T, Yang C, Ye S, Ye K, Wei D, Song Z et al (2019) Fecal microbiota transplantation alleviated Alzheimer’s disease-like pathogenesis in APP/PS1 transgenic mice. Transl Psychiat 9(1):189

    Article  Google Scholar 

  3. Kawase T, Nagasawa M, Ikeda H, Yasuo S, Koga Y, Furuse M (2017) Gut microbiota of mice putatively modifies amino acid metabolism in the host brain. Brit J Nutr 117(6):775–783

    Article  CAS  PubMed  Google Scholar 

  4. Nagpal R, Neth BJ, Wang S, Craft S, Yadav H (2019) Modified Mediterranean-ketogenic diet modulates gut microbiome and short-chain fatty acids in association with Alzheimer’s disease markers in subjects with mild cognitive impairment. EBioMedicine 47:529–542

    Article  PubMed  PubMed Central  Google Scholar 

  5. Tatulian SA (2022) Challenges and hopes for Alzheimer’s disease. Drug Discov Today 27(4):1027–1043

    Article  PubMed  Google Scholar 

  6. Liu PP, Xie Y, Meng XY, Kang JS (2019) History and progress of hypotheses and clinical trials for Alzheimer’s disease. Signal Transduct Tar 4:29

    Article  Google Scholar 

  7. Serrano-Pozo A, Das S, Hyman BT (2021) APOE and Alzheimer’s disease: advances in genetics, pathophysiology, and therapeutic approaches. Lancet Neurol 20(1):68–80

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Scheltens P, De Strooper B, Kivipelto M, Holstege H, Chételat G, Teunissen CE, Cummings J, van der Flier WM (2021) Alzheimer’s disease. Lancet 397(10284):1577–1590

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Cryan JF, O’Riordan KJ, Sandhu K, Peterson V, Dinan TG (2020) The gut microbiome in neurological disorders. Lancet Neurol 19(2):179–194

    Article  CAS  PubMed  Google Scholar 

  10. Piccioni A, Cicchinelli S, Valletta F, De Luca G, Longhitano Y, Candelli M, Ojetti V, Sardeo F, Navarra S, Covino M et al (2022) Gut microbiota and autoimmune diseases: a charming real world together with probiotics. Curr Med Chem 29(18):3147–3159

    Article  CAS  PubMed  Google Scholar 

  11. Marchesi JR, Adams DH, Fava F, Hermes GD, Hirschfield GM, Hold G, Quraishi MN, Kinross J, Smidt H, Tuohy KM et al (2016) The gut microbiota and host health: a new clinical frontier. Gut 65(2):330–339

    Article  PubMed  Google Scholar 

  12. Doifode T, Giridharan VV, Generoso JS, Bhatti G, Collodel A, Schulz PE, Forlenza OV, Barichello T (2021) The impact of the microbiota-gut-brain axis on Alzheimer’s disease pathophysiology. Pharmacol Res 164:105314

    Article  CAS  PubMed  Google Scholar 

  13. Zhu H, Zhang Y, Feng S, Li Y, Ye Y, Jian Z, Xiong X, Gu L (2023) Trends in NLRP3 inflammasome research in ischemic stroke from 2011 to 2022: a bibliometric analysis. CNS Neurosci Ther 29(10):2940–2954

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Zhang Y, Peng Y, Xia X (2023) Autoimmune diseases and gut microbiota: a bibliometric and visual analysis from 2004 to 2022. Clin Exp Med 23(6):2813–2827

    Article  PubMed  PubMed Central  Google Scholar 

  15. Chen C (2004) Searching for intellectual turning points progressive knowledge domain visualization. P Natl Acad Sci USA 101(Suppl 1): 5303–5310

  16. Massimo Aria CC (2017) bibliometrix: an R-tool for comprehensive science mapping analysis. J Informetr 11(4):959–975

    Article  Google Scholar 

  17. Zhang Y, Jia Z, Xia X, Wang J (2023) Knowledge mapping of COVID-19 and autoimmune diseases: a visual and bibliometric analysis. Clin Exp Med 23(7):3549–3564

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Wang XW, Fang ZC, Sun XL (2016) Usage patterns of scholarly articles on Web of Science: a study on Web of Science usage count. Scientometrics 109(2):917–926

    Article  Google Scholar 

  19. Cryan JF, O’Riordan KJ, Cowan C, Sandhu KV, Bastiaanssen T, Boehme M, Codagnone MG, Cussotto S, Fulling C, Golubeva AV et al (2019) The microbiota-gut-brain axis. Physiol Rev 99(4):1877–2013

    Article  CAS  PubMed  Google Scholar 

  20. Wang X, Sun G, Feng T, Zhang J, Huang X, Wang T, Xie Z, Chu X, Yang J, Wang H et al (2019) Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer’s disease progression. Cell Res 29(10):787–803

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Rinninella E, Raoul P, Cintoni M, Franceschi F, Miggiano G, Gasbarrini A, Mele MC (2019) What is the healthy gut microbiota composition? A changing ecosystem across age, environment, diet, and diseases. Microorganisms 7(1):14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Cattaneo A, Cattane N, Galluzzi S, Provasi S, Lopizzo N, Festari C, Ferrari C, Guerra UP, Paghera B, Muscio C et al (2017) Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly. Neurobiol Aging 49:60–68

    Article  CAS  PubMed  Google Scholar 

  23. Zhuang ZQ, Shen LL, Li WW, Fu X, Zeng F, Gui L, Lü Y, Cai M, Zhu C, Tan YL et al (2018) Gut microbiota is altered in patients with Alzheimer’s disease. J Alzheimers Dis 63(4):1337–1346

    Article  CAS  PubMed  Google Scholar 

  24. Jiang C, Li G, Huang P, Liu Z, Zhao B (2017) The gut microbiota and Alzheimer’s disease. J Alzheimers Dis 58(1):1–15

    Article  PubMed  Google Scholar 

  25. Colombo AV, Sadler RK, Llovera G, Singh V, Roth S, Heindl S, Sebastian ML, Verhoeven A, Peters F, Parhizkar S et al (2021) Microbiota-derived short chain fatty acids modulate microglia and promote Aβ plaque deposition. Elife 13(10):e59826

  26. Tran T, Corsini S, Kellingray L, Hegarty C, Le Gall G, Narbad A, Müller M, Tejera N, O’Toole PW, Minihane AM et al (2019) APOE genotype influences the gut microbiome structure and function in humans and mice: relevance for Alzheimer’s disease pathophysiology. FASEB J 33(7):8221–8231

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Sun J, Zhang S, Zhang X, Zhang X, Dong H, Qian Y (2015) IL-17A is implicated in lipopolysaccharide-induced neuroinflammation and cognitive impairment in aged rats via microglial activation. J Neuroinflamm 12:165

    Article  Google Scholar 

  28. André P, Laugerette F, Féart C (2019) Metabolic endotoxemia: a potential underlying mechanism of the relationship between dietary fat intake and risk for cognitive impairments in humans? Nutrients 11(8):1887

  29. Agostini A, Yuchun D, Li B, Kendall DA, Pardon MC (2020) Sex-specific hippocampal metabolic signatures at the onset of systemic inflammation with lipopolysaccharide in the APPswe/PS1dE9 mouse model of Alzheimer’s disease. Brain Behav Immun 83:87–111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Nicholson JK, Holmes E, Kinross J, Burcelin R, Gibson G, Jia W, Pettersson S (2012) Host-gut microbiota metabolic interactions. Science 336(6086):1262–1267

    Article  CAS  PubMed  Google Scholar 

  31. MahmoudianDehkordi S, Arnold M, Nho K, Ahmad S, Jia W, Xie G, Louie G, Kueider-Paisley A, Moseley MA, Thompson JW et al (2019) Altered bile acid profile associates with cognitive impairment in Alzheimer’s disease-an emerging role for gut microbiome. Alzheimers Dement 15(1):76–92

    Article  PubMed  Google Scholar 

  32. Huang F, Pariante CM, Borsini A (2022) From dried bear bile to molecular investigation: a systematic review of the effect of bile acids on cell apoptosis, oxidative stress and inflammation in the brain, across pre-clinical models of neurological, neurodegenerative and neuropsychiatric disorders. Brain Behav Immun 99:132–146

    Article  CAS  PubMed  Google Scholar 

  33. Kwon YH, Wang H, Denou E, Ghia JE, Rossi L, Fontes ME, Bernier SP, Shajib MS, Banskota S, Collins SM et al (2019) Modulation of gut microbiota composition by serotonin signaling influences intestinal immune response and susceptibility to colitis. Cell Mol Gastroenter 7(4):709–728

    Google Scholar 

  34. De-Paula VDJR, Forlenza AS, Forlenza OV (2018) Relevance of gutmicrobiota in cognition, behaviour and Alzheimer’s disease. Pharmacol Res 136:29–34

  35. Rawat K, Singh N, Kumari P, Saha L (2021) A review on preventive role of ketogenic diet (KD) in CNS disorders from the gut microbiota perspective. REV Neuroscience 32(2):143–157

    Article  CAS  Google Scholar 

  36. Mangiola F, Nicoletti A, Gasbarrini A, Ponziani FR (2018) Gut microbiota and aging. Eur Rev Med Pharmaco 22(21):7404–7413

    CAS  Google Scholar 

  37. Correale J, Hohlfeld R, Baranzini SE (2022) The role of the gut microbiota in multiple sclerosis. Nat Rev Neurol 18(9):544–558

    Article  CAS  PubMed  Google Scholar 

  38. Stoiloudis P, Kesidou E, Bakirtzis C, Sintila SA, Konstantinidou N, Boziki M, Grigoriadis N (2022) The role of diet and interventions on multiple sclerosis: a review. Nutrients 14(6):1150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Pröbstel AK, Zhou X, Baumann R, Wischnewski S, Kutza M, Rojas OL, Sellrie K, Bischof A, Kim K, Ramesh A et al (2020) Gut microbiota-specific IgA(+) B cells traffic to the CNS in active multiple sclerosis. Sci Immunol 5(53):eabc7191

  40. Sorboni SG, Moghaddam HS, Jafarzadeh-Esfehani R, Soleimanpour S (2022) A comprehensive review on the role of the gut microbiome in human neurological disorders. Clin Microbiol Rev 35(1):e0033820

    Article  PubMed  Google Scholar 

  41. Lavelle A, Sokol H (2020) Gut microbiota-derived metabolites as key actors in inflammatory bowel disease. Nat Rev Gastro Hepat 17(4):223–237

    Article  Google Scholar 

  42. Zhang B, Wang HE, Bai YM, Tsai SJ, Su TP, Chen TJ, Wang YP, Chen MH (2021) Inflammatory bowel disease is associated with higher dementia risk: a nationwide longitudinal study. Gut 70(1):85–91

    Article  PubMed  Google Scholar 

  43. Huang Y, Xu W, Zhou R (2021) NLRP3 inflammasome activation and cell death. Cell Mol Immunol 18(9):2114–2127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Milner MT, Maddugoda M, Götz J, Burgener SS, Schroder K (2021) The NLRP3 inflammasome triggers sterile neuroinflammation and Alzheimer’s disease. Curr Opin Immunol 68:116–124

    Article  CAS  PubMed  Google Scholar 

  45. Ryder MI (2020) Porphyromonas gingivalis and Alzheimer disease: recent findings and potential therapies. J Periodontol 91(Suppl 1):S45–S49

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Costa M, de Araújo I, Da RAL, Da SR, Dos SCP, Borges B, de Aquino MA, de Vasconcelos GB, Lins R (2021) Relationship of Porphyromonas gingivalis and Alzheimer’s disease: a systematic review of pre-clinical studies. Clin Oral Invest 25(3):797–806

    Article  Google Scholar 

  47. Choi J, Kim BR, Akuzum B, Chang L, Lee JY, Kwon HK (2022) T(REG)king from gut to brain: the control of regulatory T cells along the gut-brain axis. FRONT Immunol 13:916066

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Xiu R, Sun Q, Li B, Wang Y (2023) Mapping research trends and hotspots in the link between Alzheimer’s disease and gut microbes over the past decade: a bibliometric analysis. Nutrients 15(14):3203

    Article  PubMed  PubMed Central  Google Scholar 

  49. Li ZL, Ma HT, Wang M, Qian YH (2022) Research trend of microbiota-gut-brain axis in Alzheimer’s disease based on CiteSpace (2012–2021): a bibliometrics analysis of 608 articles. Front Aging Neurosci 14:1036120

    Article  PubMed  PubMed Central  Google Scholar 

  50. Trejo-Castro AI, Carrion-Alvarez D, Martinez-Torteya A, Rangel-Escareño C (2022) A bibliometric review on gut microbiome and Alzheimer’s disease between 2012 and 2021. Front Aging Neurosci 14:804177

    Article  PubMed  PubMed Central  Google Scholar 

  51. Karri S, Acosta-Martinez V, Coimbatore G (2010) Effect of dihydrotestosterone on gastrointestinal tract of male Alzheimer’s disease transgenic mice. Indian J Exp Biol 48(5):453–465

    CAS  PubMed  Google Scholar 

  52. Fan L, Mao C, Hu X, Zhang S, Yang Z, Hu Z, Sun H, Fan Y, Dong Y, Yang J et al (2019) New insights into the pathogenesis of Alzheimer’s disease. Front Neurol 10:1312

    Article  PubMed  Google Scholar 

  53. Sjogren T, Sjogren H, Lindgren AG (1952) Morbus Alzheimer and morbus Pick; a genetic, clinical and patho-anatomical study. Acta Psychiatr Neurol Scand Suppl 82:1–152

    CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported by the Special Fund Project for Science and Technology Innovation Strategy of Guangdong Province (grant number pdjh2023b0107) and National College Students Innovation and Entrepreneurship Training Program (grant number 202212121008), Medical Research Foundation of Guangdong Province (grant number A2022362), Shenzhen Science and Technology Planning Project (grant number JCYJ20220530165014033), Medical research project of Shenzhen Longhua Medical Association (2023LHMA10), the Scientific Research Projects of Medical and Health Institutions of Longhua District, Shenzhen (grant number 2021017), and Shenzhen Medical Key Discipline (grant number MKD202007090201).

Author information

Authors and Affiliations

  1. Department of Urology, People’s Hospital of Longhua, No.38 Jinglong Jianshe Road, 518109, Shenzhen, China

    Youao Zhang, Jieyan Wang & Hui Liang

  2. The First School of Clinical Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China

    Youao Zhang

  3. School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China

    Zixuan Jia

Authors
  1. Youao Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zixuan Jia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jieyan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hui Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Y.Z. Conceptualization, Methodology, Investigation, Writing, Reviewing and Editing. Z.J. Drawing, Reviewing and Editing J.W. Methodology, Fund support, Reviewing and Editing. H.L. Fund support, Reviewing and Editing.

Corresponding authors

Correspondence to Jieyan Wang or Hui Liang.

Ethics declarations

Ethical Approval

The data are all from the public database Web of Science, which does not involve ethical issues.

Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

Competing Interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, Y., Jia, Z., Wang, J. et al. Research Hotspots and Frontiers of Alzheimer’s Disease and Gut Microbiota: A Knowledge Mapping and Text Mining Analysis. Mol Neurobiol (2024). https://doi.org/10.1007/s12035-024-04168-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12035-024-04168-7

Keywords

Search

Navigation