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Regulation of blood–brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine N-oxide

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Hoyles, Lesley, Pontifex, Matthew G., Rodriguez-Ramiro, Ildefonso, Anis-Alavi, M. Areeb, Jelane, Khadija S., Snelling, Tom, Solito, Egle, Fonseca, Sonia, Carvalho, Ana L., Carding, Simon R., Müller, Michael, Glen, Robert C., Vauzour, David, McArthur, Simon·2021·Microbiome
DOI 10.1186/s40168-021-01181-zPMC PMC8626999

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Abstract

BACKGROUND: Communication between the gut microbiota and the brain is primarily mediated via soluble microbe-derived metabolites, but the details of this pathway remain poorly defined. Methylamines produced by microbial metabolism of dietary choline and L-carnitine have received attention due to their proposed association with vascular disease, but their effects upon the cerebrovascular circulation have hitherto not been studied. RESULTS: Here, we use an integrated in vitro/in vivo approach to show that physiologically relevant concentrations of the dietary methylamine trimethylamine N-oxide (TMAO) enhanced blood-brain barrier (BBB) integrity and protected it from inflammatory insult, acting through the tight junction regulator annexin A1. In contrast, the TMAO precursor trimethylamine (TMA) impaired BBB function and disrupted tight junction integrity. Moreover, we show that long-term exposure to TMAO protects murine cognitive function from inflammatory challenge, acting to limit astrocyte and microglial reactivity in a brain region-specific manner. CONCLUSION: Our findings demonstrate the mechanisms through which microbiome-associated methylamines directly interact with the mammalian BBB, with consequences for cerebrovascular and cognitive function. Video abstract.

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  1. Braniste V, Al-Asmakh M, Kowal C, Anuar F, Abbaspour A, Tóth M, et al. The gut microbiota influences blood-brain barrier permeability in mice. Sci Transl Med. 2014;6:263ra158. · DOI · Paper page
  2. Tang WHW, Hazen SL. Microbiome, trimethylamine N-oxide, and cardiometabolic disease. Transl Res. 2017;179:108–15. https://doi.org/10.1016/j.trsl.2016.07.007. · DOI · Paper page
  3. Dinicolantonio JJ, McCarty M, Okeefe J. Association of moderately elevated trimethylamine N-oxide with cardiovascular risk: is TMAO serving as a marker for hepatic insulin resistance. Open Heart. 2019;6(1):–e000890. https://doi.org/10.1136/openhrt-2018-000890. · DOI
  4. Hoyles L, Jimenez-Pranteda ML, Chilloux J, Brial F, Myridakis A, Aranias T, et al. Metabolic retroconversion of trimethylamine N-oxide and the gut microbiota. Microbiome. 2018;6(1):73. https://doi.org/10.1186/s40168-018-0461-0. · DOI
  5. Duranton F, Cohen G, De Smet R, Rodriguez M, Jankowski J, Vanholder R, et al. Normal and pathologic concentrations of uremic toxins. J Am Soc Nephrol. 2012;23(7):1258–70. https://doi.org/10.1681/ASN.2011121175. · DOI
  6. Bain M, Faull R, Fornasini G, Milne R, Evans A. Accumulation of trimethylamine and trimethylamine-N-oxide in end-stage renal disease patients undergoing haemodialysis. Nephrol Dial Transplant. 2006;21(5):1300–4. https://doi.org/10.1093/ndt/gfk056. · DOI · Paper page
  7. Tang WHW, Wang Z, Fan Y, Levison B, Hazen JE, Donahue LM, et al. Prognostic value of elevated levels of intestinal microbe-generated metabolite trimethylamine-N-oxide in patients with heart failure: refining the gut hypothesis. J Am Coll Cardiol. 2014;64(18):1908–14. https://doi.org/10.1016/j.jacc.2014.02.617. · DOI · Paper page
  8. Wang Z, Roberts AB, Buffa JA, Levison BS, Zhu W, Org E, et al. Non-lethal inhibition of gut microbial trimethylamine production for the treatment of atherosclerosis. Cell. 2015;163(7):1585–95. https://doi.org/10.1016/j.cell.2015.11.055. · DOI · Paper page
  9. Zhu W, Gregory JC, Org E, Buffa JA, Gupta N, Wang Z, et al. Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk. Cell. 2016;165(1):111–24. https://doi.org/10.1016/j.cell.2016.02.011. · DOI · Paper page
  10. Jia J, Dou P, Gao M, Kong X, Li C, Liu Z, et al. Assessment of causal direction between gut microbiota-dependent metabolites and cardiometabolic health: a bi-directional Mendelian randomisation analysis. Diabetes. 2019;68(9):1747–55. https://doi.org/10.2337/db19-0153. · DOI
  11. Winther SA, Ollgaard JC, Tofte N, Tarnow L, Wang Z, Ahluwalia TS, et al. Utility of Plasma concentration of trimethylamine N-oxide in predicting cardiovascular and renal complications in individuals with type 1 diabetes. Diabetes Care. 2019;42(8):1512–20. https://doi.org/10.2337/dc19-0048. · DOI
  12. Huc T, Drapala A, Gawrys M, Konop M, Bielinska K, Zaorska E, et al. Chronic, low-dose TMAO treatment reduces diastolic dysfunction and heart fibrosis in hypertensive rats. Am J Physiol. 2018;315(6):H1805–20. https://doi.org/10.1152/ajpheart.00536.2018. · DOI
  13. Zhao Z-H, Xin F-Z, Zhou D, Xue Y-Q, Liu X-L, Yang R-X, et al. Trimethylamine N-oxide attenuates high-fat high-cholesterol diet-induced steatohepatitis by reducing hepatic cholesterol overload in rats. World J Gastroenterol. 2019;25(20):2450–62. https://doi.org/10.3748/wjg.v25.i20.2450. · DOI
  14. Jaworska K, Bielinska K, Gawrys-Kopczynska M, Ufnal M. TMA (trimethylamine), but not its oxide TMAO (trimethylamine-oxide), exerts haemodynamic effects: implications for interpretation of cardiovascular actions of gut microbiome. Cardiovasc Res. 2019;115(14):1948–9. https://doi.org/10.1093/cvr/cvz231. · DOI
  15. Huo X, Li J, Cao Y-F, Li S-N, Shao P, Leng J, et al. Trimethylamine N-oxide metabolites in early pregnancy and risk of gestational diabetes: a nested case-control study. J Clin Endocrinol Metab. 2019;104(11):5529–39. https://doi.org/10.1210/jc.2019-00710. · DOI
  16. Poly C, Massaro JM, Seshadri S, Wolf PA, Cho E, Krall E, et al. The relation of dietary choline to cognitive performance and white-matter hyperintensity in the Framingham Offspring Cohort. Am J Clin Nutr. 2011;94(6):1584–91. https://doi.org/10.3945/ajcn.110.008938. · DOI · Paper page
  17. Nurk E, Refsum H, Bjelland I, Drevon CA, Tell GS, Ueland PM, et al. Plasma free choline, betaine and cognitive performance: the Hordaland Health Study. Br J Nutr. 2013;109(3):511–9. https://doi.org/10.1017/S0007114512001249. · DOI · Paper page
  18. Leathwood PD, Heck E, Mauron J. Phosphatidyl choline and avoidance performance in 17 month-old SEC/1ReJ mice. Life Sci. 1982;30(13):1065–71. https://doi.org/10.1016/0024-3205(82)90526-4. · DOI
  19. Bartus RT, Dean RL, Goas JA, Lippa AS. Age-related changes in passive avoidance retention: modulation with dietary choline. Science. 1980;209(4453):301–3. https://doi.org/10.1126/science.7384805. · DOI
  20. Vogt NM, Romano KA, Darst BF, Engelman CD, Johnson SC, Carlsson CM, et al. The gut microbiota-derived metabolite trimethylamine N-oxide is elevated in Alzheimer’s disease. Alzheimers Res Ther. 2018;10(1):124. https://doi.org/10.1186/s13195-018-0451-2. · DOI · Paper page
  21. Gao Q, Wang Y, Wang X, Fu S, Zhang X, Wang RT, et al. Decreased levels of circulating trimethylamine N-oxide alleviate cognitive and pathological deterioration in transgenic mice: a potential therapeutic approach for Alzheimer’s disease. Aging. 2019;11(19):8642–63. https://doi.org/10.18632/aging.102352. · DOI
  22. Weksler BB, Subileau EA, Perrière N, Charneau P, Holloway K, Leveque M, et al. Blood-brain barrier-specific properties of a human adult brain endothelial cell line. FASEB J. 2005;19(13):1872–4. https://doi.org/10.1096/fj.04-3458fje. · DOI
  23. Maggioli E, McArthur S, Mauro C, Kieswich J, Kusters DHM, Reutelingsperger CPM, et al. Estrogen protects the blood-brain barrier from inflammation-induced disruption and increased lymphocyte trafficking. Brain Behav Immun. 2015;51:212–22. https://doi.org/10.1016/j.bbi.2015.08.020. · DOI
  24. Abbott NJ, Hughes CC, Revest PA, Greenwood J. Development and characterisation of a rat brain capillary endothelial culture: towards an in vitro blood-brain barrier. J Cell Sci. 1992;103(Pt 1):23–37. · DOI
  25. Coisne C, Dehouck L, Faveeuw C, Delplace Y, Miller F, Landry C, et al. Mouse syngenic in vitro blood-brain barrier model: a new tool to examine inflammatory events in cerebral endothelium. Lab Investig J Tech Methods Pathol. 2005;85(6):734–46. https://doi.org/10.1038/labinvest.3700281. · DOI
  26. Pais de Barros J-P, Gautier T, Sali W, Adrie C, Choubley H, Charron E, et al. Quantitative lipopolysaccharide analysis using HPLC/MS/MS and its combination with the limulus amebocyte lysate assay. J Lipid Res. 2015, 56:1363–9. · DOI
  27. Gautier L, Cope L, Bolstad BM, Irizarry RA. affy--analysis of Affymetrix GeneChip data at the probe level. Bioinforma. 2004;20(3):307–15. https://doi.org/10.1093/bioinformatics/btg405. · DOI
  28. Kuleshov MV, Jones MR, Rouillard AD, Fernandez NF, Duan Q, Wang Z, et al. Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res. 2016;44(W1):W90–7. https://doi.org/10.1093/nar/gkw377. · DOI · Paper page
  29. Zhang JD, Wiemann S. KEGGgraph: a graph approach to KEGG PATHWAY in R and bioconductor. Bioinforma. 2009;25(11):1470–1. https://doi.org/10.1093/bioinformatics/btp167. · DOI
  30. McArthur S, Cristante E, Paterno M, Christian H, Roncaroli F, Gillies GEE, et al. Annexin A1: a central player in the anti-inflammatory and neuroprotective role of microglia. J Immunol. 2010;185(10):6317–28. https://doi.org/10.4049/jimmunol.1001095. · DOI
  31. Wishart DS, Feunang YD, Marcu A, Guo AC, Liang K, Vázquez-Fresno R, et al. HMDB 4.0: the human metabolome database for 2018. Nucleic Acids Res. 2018;46(D1):D608–17. https://doi.org/10.1093/nar/gkx1089. · DOI · Paper page
  32. Marottoli FM, Katsumata Y, Koster KP, Thomas R, Fardo DW, Tai LM. Peripheral inflammation, apolipoprotein E4, and amyloid-β Interact to induce cognitive and cerebrovascular dysfunction. ASN Neuro. 2017;9:1759091417719201. · DOI
  33. Kim D, Langmead B, Salzberg SL. HISAT: a fast spliced aligner with low memory requirements. Nat Methods. 2015;12(4):357–60. https://doi.org/10.1038/nmeth.3317. · DOI · Paper page
  34. Hölter SM, Einicke J, Sperling B, Zimprich A, Garrett L, Fuchs H, et al. Tests for Anxiety-Related Behavior in Mice. Curr Protoc Mouse Biol. 2015;5(4):291–309. https://doi.org/10.1002/9780470942390.mo150010. · DOI
  35. Davis KE, Eacott MJ, Easton A, Gigg J. Episodic-like memory is sensitive to both Alzheimer’s-like pathological accumulation and normal ageing processes in mice. Behav Brain Res. 2013;254:73–82. https://doi.org/10.1016/j.bbr.2013.03.009. · DOI · Paper page
  36. Leger M, Quiedeville A, Bouet V, Haelewyn B, Boulouard M, Schumann-Bard P, et al. Object recognition test in mice. Nat Protoc. 2013;8(12):2531–7. https://doi.org/10.1038/nprot.2013.155. · DOI · Paper page
  37. Denninger JK, Smith BM, Kirby ED. Novel object recognition and object location behavioral testing in mice on a budget. J Vis Exp. 2018;(141). https://doi.org/10.3791/58593. · DOI
  38. Thomas R, Morris AWJ, Tai LM. Epidermal growth factor prevents APOE4-induced cognitive and cerebrovascular deficits in female mice. Heliyon. 2017;3(6):e00319. https://doi.org/10.1016/j.heliyon.2017.e00319. · DOI
  39. Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43(7):e47. https://doi.org/10.1093/nar/gkv007. · DOI · Paper page
  40. Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15(12):550. https://doi.org/10.1186/s13059-014-0550-8. · DOI · Paper page
  41. Lochhead JJ, Yang J, Ronaldson PT, Davis TP. Structure, function, and regulation of the blood-brain barrier tight junction in central nervous system disorders. Front Physiol. 2020;11:914. https://doi.org/10.3389/fphys.2020.00914. · DOI · Paper page
  42. Cristante E, McArthur S, Mauro C, Maggioli E, Romero IAIA, Wylezinska-Arridge M, et al. Identification of an essential endogenous regulator of blood-brain barrier integrity, and its pathological and therapeutic implications. Proc Natl Acad Sci U S A. 110:832–41. · DOI
  43. McArthur S, Yazid S, Christian H, Sirha R, Flower R, Buckingham J, et al. Annexin A1 regulates hormone exocytosis through a mechanism involving actin reorganization. FASEB J. 2009;23(11):4000–10. https://doi.org/10.1096/fj.09-131391. · DOI
  44. Bena S, Brancaleone V, Wang JM, Perretti M, Flower RJ. Annexin A1 interaction with the FPR2/ALX receptor: identification of distinct domains and downstream associated signaling. J Biol Chem. 2012;287(29):24690–7. https://doi.org/10.1074/jbc.M112.377101. · DOI
  45. Cho CE, Taesuwan S, Malysheva OV, Bender E, Tulchinsky NF, Yan J, et al. Trimethylamine-N-oxide (TMAO) response to animal source foods varies among healthy young men and is influenced by their gut microbiota composition: A randomized controlled trial. Mol Nutr Food Res. 2017;61(1):1600324. https://doi.org/10.1002/mnfr.201600324. · DOI · Paper page
  46. Trigiani LJ, Bourourou M, Lacalle-Aurioles M, Lecrux C, Hynes A, Spring S, et al. A functional cerebral endothelium is necessary to protect against cognitive decline. J Cereb Blood Flow Metab. 2021. https://doi.org/10.1177/0271678X211045438. · DOI
  47. Cohen SJ, Stackman RW. Assessing rodent hippocampal involvement in the novel object recognition task. A review. Behav Brain Res. 2015;285:105–17. https://doi.org/10.1016/j.bbr.2014.08.002. · DOI
  48. Wilson DIG, Langston RF, Schlesiger MI, Wagner M, Watanabe S, Ainge JA. Lateral entorhinal cortex is critical for novel object-context recognition. Hippocampus. 2013;23(5):352–66. https://doi.org/10.1002/hipo.22095. · DOI
  49. Merino JG, Latour LL, Tso A, Lee KY, Kang DW, Davis LA, et al. Blood-brain barrier disruption after cardiac surgery. Am J Neuroradiol. 2013;34(3):518–23. https://doi.org/10.3174/ajnr.A3251. · DOI
  50. Hu N, Guo D, Wang H, Xie K, Wang C, Li Y, et al. Involvement of the blood-brain barrier opening in cognitive decline in aged rats following orthopedic surgery and high concentration of sevoflurane inhalation. Brain Res. 2014;1551:13–24. https://doi.org/10.1016/j.brainres.2014.01.015. · DOI
  51. Abrahamov D, Levran O, Naparstek S, Refaeli Y, Kaptson S, Abu Salah M, et al. Blood-brain barrier disruption after cardiopulmonary bypass: diagnosis and correlation to cognition. Ann Thorac Surg. 2017;104(1):161–9. https://doi.org/10.1016/j.athoracsur.2016.10.043. · DOI
  52. Yang S, Gu C, Mandeville ET, Dong Y, Esposito E, Zhang Y, et al. Anesthesia and surgery impair blood-brain barrier and cognitive function in mice. Front Immunol. 2017;8:902. https://doi.org/10.3389/fimmu.2017.00902. · DOI
  53. Zenaro E, Piacentino G, Constantin G. The blood-brain barrier in Alzheimer’s disease. Neurobiol Dis. 2016;107:41–56. https://doi.org/10.1016/j.nbd.2016.07.007. · DOI · Paper page
  54. Brunt VE, LaRocca TJ, Bazzoni AE, Sapinsley ZJ, Miyamoto-Ditmon J, Gioscia-Ryan RA, et al. The gut microbiome-derived metabolite trimethylamine N-oxide modulates neuroinflammation and cognitive function with aging. GeroScience. 2021;43(1):377–94. https://doi.org/10.1007/s11357-020-00257-2. · DOI · Paper page
  55. Su H, Fan S, Zhang L, Qi H. TMAO aggregates neurological damage following ischemic stroke by promoting reactive astrocytosis and glial scar formation via the Smurf2/ALK5 axis. Front Cell Neurosci. 2021;15:569424. https://doi.org/10.3389/fncel.2021.569424. · DOI
  56. Zhao L, Zhang C, Cao G, Dong X, Li D, Jiang L. Higher circulating trimethylamine N-oxide sensitizes sevoflurane-induced cognitive dysfunction in aged rats probably by downregulating hippocampal methionine sulfoxide reductase A. Neurochem Res. 2019;44(11):2506–16. https://doi.org/10.1007/s11064-019-02868-4. · DOI
  57. Meng F, Li N, Li D, Song B, Li L. The presence of elevated circulating trimethylamine N-oxide exaggerates postoperative cognitive dysfunction in aged rats. Behav Brain Res. 2019;368:–111902. https://doi.org/10.1016/j.bbr.2019.111902. · DOI
  58. Frías-Anaya E, Gromnicova R, Kraev I, Rogachevsky V, Male DK, Crea F, et al. Age-related ultrastructural neurovascular changes in the female mouse cortex and hippocampus. Neurobiol Aging. 2021;101:273–84. https://doi.org/10.1016/j.neurobiolaging.2020.12.008. · DOI
  59. Schaffenrath J, Huang S-F, Wyss T, Delorenzi M, Keller A. Characterization of the blood-brain barrier in genetically diverse laboratory mouse strains. Fluids Barriers CNS. 2021;18(1):34. https://doi.org/10.1186/s12987-021-00269-w. · DOI
  60. He W, Luo Y, Liu J-P, Sun N, Guo D, Cui L-L, et al. Trimethylamine N-oxide, a gut microbiota-dependent metabolite, is associated with frailty in older adults with cardiovascular disease. Clin Interv Aging. 2020;15:1809–20. https://doi.org/10.2147/CIA.S270887. · DOI
  61. Zhu C, Li G, Lv Z, Li J, Wang X, Kang J, et al. Association of plasma trimethylamine-N-oxide levels with post-stroke cognitive impairment: a 1-year longitudinal study. Neurol Sci. 2020;41(1):57–63. https://doi.org/10.1007/s10072-019-04040-w. · DOI
  62. Sanguinetti E, Collado MC, Marrachelli VG, Monleon D, Selma-Royo M, Pardo-Tendero MM, et al. Microbiome-metabolome signatures in mice genetically prone to develop dementia, fed a normal or fatty diet. Sci Rep. 2018;8(1):4907. https://doi.org/10.1038/s41598-018-23261-1. · DOI
  63. Liu J, Zhang T, Wang Y, Si C, Wang X, Wang R-T, et al. Baicalin ameliorates neuropathology in repeated cerebral ischemia-reperfusion injury model mice by remodeling the gut microbiota. Aging. 2020;12(4):3791–806. https://doi.org/10.18632/aging.102846. · DOI
  64. Wang Q-J, Shen Y-E, Wang X, Fu S, Zhang X, Zhang Y-N, et al. Concomitant memantine and Lactobacillus plantarum treatment attenuates cognitive impairments in APP/PS1 mice. Aging. 2020;12(1):628–49. https://doi.org/10.18632/aging.102645. · DOI
  65. Sawicka AK, Renzi G, Olek RA. The bright and the dark sides of L-carnitine supplementation: a systematic review. J Int Soc Sports Nutr. 2020;17(1):49. https://doi.org/10.1186/s12970-020-00377-2. · DOI
  66. Papandreou C, Moré M, Bellamine A. Trimethylamine N-oxide in relation to cardiometabolic health-cause or effect? Nutrients. 2020;12(5). https://doi.org/10.3390/nu12051330. · DOI
  67. Zeisel SH. Dietary choline: biochemistry, physiology, and pharmacology. Annu Rev Nutr. 1981;1(1):95–121. https://doi.org/10.1146/annurev.nu.01.070181.000523. · DOI
  68. Lundstrom RC, Racicot LD. Gas chromatographic determination of dimethylamine and trimethylamine in seafoods. J Assoc Off Anal Chem. 1983;66:1158–63.
  69. Zeng L-F, Cao Y, Liang W-X, Bao W-H, Pan J-K, Wang Q, et al. An exploration of the role of a fish-oriented diet in cognitive decline: a systematic review of the literature. Oncotarget. 2017;8(24):39877–95. https://doi.org/10.18632/oncotarget.16347. · DOI
  70. Keenan TD, Agrón E, Mares JA, Clemons TE, van Asten F, Swaroop A, et al. Adherence to a Mediterranean diet and cognitive function in the Age-Related Eye Disease Studies 1 & 2. Alzheimers Dement. 2020;16(6):831–42. https://doi.org/10.1002/alz.12077. · DOI
  71. Zhao W, Tang H, Yang X, Luo X, Wang X, Shao C, et al. Fish consumption and stroke risk: a meta-analysis of prospective cohort studies. J Stroke Cerebrovasc Dis. 2019;28(3):604–11. https://doi.org/10.1016/j.jstrokecerebrovasdis.2018.10.036. · DOI
  72. Zhang Y, Chen J, Qiu J, Li Y, Wang J, Jiao J. Intakes of fish and polyunsaturated fatty acids and mild-to-severe cognitive impairment risks: a dose-response meta-analysis of 21 cohort studies. Am J Clin Nutr. 2016;103(2):330–40. https://doi.org/10.3945/ajcn.115.124081. · DOI · Paper page
  73. Cooper RE, Tye C, Kuntsi J, Vassos E, Asherson P. Omega-3 polyunsaturated fatty acid supplementation and cognition: a systematic review and meta-analysis. J Psychopharmacol. 2015;29(7):753–63. https://doi.org/10.1177/0269881115587958. · DOI
  74. Abdelhamid AS, Brown TJ, Brainard JS, Biswas P, Thorpe GC, Moore HJ, et al. Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2018;11:CD003177. https://doi.org/10.1002/14651858.CD003177.pub3. · DOI
  75. Wall R, Ross RP, Fitzgerald GF, Stanton C. Fatty acids from fish: the anti-inflammatory potential of long-chain omega-3 fatty acids. Nutr Rev. 2010;68(5):280–9. https://doi.org/10.1111/j.1753-4887.2010.00287.x. · DOI · Paper page
  76. Singh AK, Jiang Y. How does peripheral lipopolysaccharide induce gene expression in the brain of rats? Toxicology. 2004;201(1-3):197–207. https://doi.org/10.1016/j.tox.2004.04.015. · DOI
  77. Gobbetti T, Cooray SN. Annexin A1 and resolution of inflammation: tissue repairing properties and signalling signature. Biol Chem. 2016;397(10):981–93. https://doi.org/10.1515/hsz-2016-0200. · DOI
  78. Needham BD, Kaddurah-Daouk R, Mazmanian SK. Gut microbial molecules in behavioural and neurodegenerative conditions. Nat Rev Neurosci. 2020;21(12):717–31. https://doi.org/10.1038/s41583-020-00381-0. · DOI · Paper page

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Authors
Hoyles, L., Pontifex, M. G., Rodriguez-Ramiro, I., Anis-Alavi, M. A., Jelane, K. S., Snelling, T., Solito, E., Fonseca, S., Carvalho, A. L., Carding, S. R., Müller, M., Glen, R. C., Vauzour, D., & McArthur, S.
Affiliations
  • Nottingham Trent University (GB)
  • University of East Anglia (GB)
  • Queen Mary University of London (GB)
  • Imperial College London (GB)
  • Norwich Research Park (GB)
  • University of Cambridge (GB)
Corresponding author
  • Hoyles, Lesley
  • McArthur, Simon
ORCID
Venue
Microbiome
Publisher
Springer Science and Business Media LLC
Published
2021-11-27
Volume
9
Issue
1
Pages
235-235
ISSN
2049-2618 (ISSN-L)
DOI
10.1186/s40168-021-01181-z
PMC
PMC8626999
OpenAlex
W3203565491
Cited by
221
References
16
Citations by year
2026: 41 · 2025: 68 · 2024: 54 · 2023: 32 · 2022: 25
FWCI
11.18
Type
journal article
Language
en
Open access
Licence
Locations
  • Microbiome (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Nottingham Trent University's Institutional Repository (Nottingham Trent Repository) (acceptedVersion)
  • UEA Digital Repository (University of East Anglia) (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Queen Mary Research Online (Queen Mary University of London) (submittedVersion, cc-by)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • Apollo
  • Apollo (cc-by)
Funders
  • Alzheimer's Research UK (ARUK-PPG2016B-6)
  • Solvo Biotechnology (ReACTS Program)
  • Medical Research Council (MR/L01632X/1)
  • Imperial College London (Undergraduate Research Opportunities Programme)
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Keywords
trimethylamine N-oxide, trimethylamine, blood-brain barrier integrity, gut microbiota, methylamine, choline metabolism, L-carnitine, tight junctions, annexin A1, neuroinflammation, cognitive function, astrocytes, microglia, cerebrovascular function, microbiota-brain axis
MeSH terms
Animals, Blood-Brain Barrier, Cognition, Mammals, Methylamines, Mice, Microbiota

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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