Top

Published in:

01-01-2021 | Glaucoma | Original Paper

Glaucoma patients have an increased level of trimethylamine, a toxic product of gut bacteria, in the aqueous humor: a pilot study

Authors: Janusz Skrzypecki, J. Izdebska, A. Kamińska, J. Badowska, J. Przybek-Skrzypecka, J. Bombuy, E. Samborowska, J. P. Szaflik

Published in: International Ophthalmology | Issue 1/2021

Abstract

Purpose

Animal studies suggest that gut bacteria metabolites are involved in regulation of intraocular pressure or development of glaucoma. However, clinical data are lacking. Here, we wanted to compare level of trimethylamine (TMA), an uremic toxin produced by gut bacteria, along with betaine and trimethylamine N-oxide (TMAO), a substrate and a product of its metabolism, in the aqueous humor and in plasma of patients with glaucoma and their controls.

Methods

Twenty patients were selected for cataract phacoemulsification, and 20 patients selected for phacotrabeculectomy were enrolled in the study. Patients were matched with controls on systemic diseases and estimated glomerular filtration rate. Blood samples were collected in the preoperative suite, whereas aqueous humor samples were collected as the first step of both procedures. Subsequently, level of betaine, TMA and TMAO was analyzed by means of chromatography.

Results

In the aqueous humor, level of TMA, but not betaine or TMAO, was significantly higher in the phacotrabeculectomy group than in the phacoemulsification group. Plasma level of betaine, TMA and TMAO was similar between groups. In both groups, level of betaine and TMA, but not TMAO, was significantly higher in plasma than in the aqueous humor.

Conclusion

TMA, but not TMAO or betaine level, is increased in the aqueous humor of patients with glaucoma. TMA might play a role in pathogenesis of glaucoma; however, prospective studies are needed to confirm our findings.

Martinez KB, Leone V, Chang EB (2017) Microbial metabolites in health and disease: navigating the unknown in search of function. J Biol Chem 292:8553–8559. https://doi.org/10.1074/jbc.R116.752899CrossRefPubMedPubMedCentral

Russell WR, Hoyles L, Flint HJ, Dumas ME (2013) Colonic bacterial metabolites and human health. Curr Opin Microbiol 16:246–254. https://doi.org/10.1016/j.mib.2013.07.002CrossRefPubMed

Skrzypecki J, Zera T, Ufnal M (2018) Butyrate, a gut bacterial metabolite, lowers intraocular pressure in normotensive but not in hypertensive rats. J Glaucoma 27:823–827. https://doi.org/10.1097/IJG.0000000000001025CrossRefPubMed

Jia LY, Gong B, Pang CP, Huang Y, Lam DS, Wang N et al (2009) Correction of the disease phenotype of myocilin-causing glaucoma by a natural osmolyte. Invest Ophthalmol Vis Sci 50:3743–3749. https://doi.org/10.1167/iovs.08-3151CrossRefPubMed

Salvi A, Bankhele P, Jamil J, Chitnis MK, Njie-Mbye YF, Ohia SE et al (2016) Effect of hydrogen sulfide donors on intraocular pressure in rabbits. J Ocul Pharmacol Ther 32:371–375. https://doi.org/10.1089/jop.2015.0144CrossRefPubMedPubMedCentral

Huc T, Drapala A, Gawrys M, Konop M, Bielinska K, Zaorska E et al (2018) Chronic, low-dose TMAO treatment reduces diastolic dysfunction and heart fibrosis in hypertensive rats. Am J Physiol Heart Circ Physiol 315:H1805–H1820. https://doi.org/10.1152/ajpheart.00536.2018CrossRefPubMed

Ufnal M, Nowinski A (2019) Is increased plasma TMAO a compensatory response to hydrostatic and osmotic stress in cardiovascular diseases? Med Hypotheses 130:109271. https://doi.org/10.1016/j.mehy.2019.109271CrossRefPubMed

Ufnal M, Zadlo A, Ostaszewski R (2015) TMAO: a small molecule of great expectations. Nutrition 31:1317–1323. https://doi.org/10.1016/j.nut.2015.05.006CrossRefPubMed

Jaworska K, Konop M, Hutsch T, Perlejewski K, Radkowski M, Grochowska M et al (2019) TMA but not TMAO increases with age in rat plasma and affects smooth muscle cells viability. J Gerontol A Biol Sci Med Sci. https://doi.org/10.1093/gerona/glz181CrossRef

10.

Jaworska K, Hering D, Mosieniak G, Bielak-Zmijewska A, Pilz M, Konwerski M et al (2019) TMA, a forgotten uremic toxin, but not TMAO, is involved in cardiovascular pathology. Toxins (Basel) 11:490. https://doi.org/10.3390/toxins11090490CrossRef

11.

Hamdane D, Velours C, Cornu D, Nicaise M, Lombard M, Fontecave M (2016) A chemical chaperone induces inhomogeneous conformational changes in flexible proteins. Phys Chem Chem Phys 18:20410–20421. https://doi.org/10.1039/c6cp03635jCrossRefPubMed

12.

Jaworska K, Konop M, Hutsch T, Perlejewski K, Radkowski M, Grochowska M et al (2020) Trimethylamine but not trimethylamine oxide increases with age in rat plasma and affects smooth muscle cells viability. J Gerontol A Biol Sci Med Sci 75:1276–1283. https://doi.org/10.1093/gerona/glz181CrossRefPubMed

13.

Jovanovic P, Zoric L, Stefanovic I, Dzunic B, Djordjevic-Jocic J, Radenkovic M et al (2010) Lactate dehydrogenase and oxidative stress activity in primary open-angle glaucoma aqueous humour. Bosn J Basic Med Sci 10:83–88. https://doi.org/10.17305/bjbms.2010.2743CrossRefPubMedPubMedCentral

14.

Kaeslin MA, Killer HE, Fuhrer CA, Zeleny N, Huber AR, Neutzner A (2016) Changes to the aqueous humor proteome during glaucoma. PLoS ONE 11:e0165314. https://doi.org/10.1371/journal.pone.0165314CrossRefPubMedPubMedCentral

15.

Pevsner-Fischer M, Blacher E, Tatirovsky E, Ben-Dov IZ, Elinav E (2017) The gut microbiome and hypertension. Curr Opin Nephrol Hypertens 26:1–8. https://doi.org/10.1097/MNH.0000000000000293CrossRefPubMed

16.

Jaworska K, Bielinska K, Gawrys-Kopczynska M, Ufnal M (2019) TMA (trimethylamine), but not its oxide TMAO (trimethylamine-oxide), exerts haemodynamic effects: implications for interpretation of cardiovascular actions of gut microbiome. Cardiovasc Res 115:1948–1949. https://doi.org/10.1093/cvr/cvz231CrossRefPubMed

17.

Ufnal M, Jazwiec R, Dadlez M, Drapala A, Sikora M, Skrzypecki J (2014) Trimethylamine-N-oxide: a carnitine-derived metabolite that prolongs the hypertensive effect of angiotensin II in rats. Can J Cardiol 30:1700–1705. https://doi.org/10.1016/j.cjca.2014.09.010CrossRefPubMed

18.

He Z, Vingrys AJ, Armitage JA, Bui BV (2011) The role of blood pressure in glaucoma. Clin Exp Optom 94:133–149. https://doi.org/10.1111/j.1444-0938.2010.00564.xCrossRefPubMed

19.

Fuchs FD, Whelton PK (2020) High blood pressure and cardiovascular disease. Hypertension 75:285–292. https://doi.org/10.1161/HYPERTENSIONAHA.119.14240CrossRefPubMed

20.

Jeganathan VS, Wong TY, Foster PJ, Crowston JG, Tay WT, Lim SC et al (2009) Peripheral artery disease and glaucoma: the singapore malay eye study. Arch Ophthalmol 127:888–893. https://doi.org/10.1001/archophthalmol.2009.136CrossRefPubMed

21.

Ma J, Li H (2018) The role of gut microbiota in atherosclerosis and hypertension. Front Pharmacol 9:1082. https://doi.org/10.3389/fphar.2018.01082CrossRefPubMedPubMedCentral

22.

Geng J, Yang C, Wang B, Zhang X, Hu T, Gu Y et al (2018) Trimethylamine N-oxide promotes atherosclerosis via CD36-dependent MAPK/JNK pathway. Biomed Pharmacother 97:941–947. https://doi.org/10.1016/j.biopha.2017.11.016CrossRefPubMed

23.

Craig SA (2004) Betaine in human nutrition. Am J Clin Nutr 80:539–549. https://doi.org/10.1093/ajcn/80.3.539CrossRefPubMed

24.

Flanagan JL, Simmons PA, Vehige J, Willcox MD, Garrett Q (2010) Role of carnitine in disease. Nutr Metab (Lond) 7:30. https://doi.org/10.1186/1743-7075-7-30CrossRef

25.

Janeiro MH, Ramirez MJ, Milagro FI, Martinez JA, Solas M (2018) Implication of trimethylamine N-Oxide (TMAO) in disease: potential biomarker or new therapeutic target. Nutrients 10:1398. https://doi.org/10.3390/nu10101398CrossRefPubMedCentral

26.

Nowinski A, Ufnal M (2018) Trimethylamine N-oxide: a harmful, protective or diagnostic marker in lifestyle diseases? Nutrition 46:7–12. https://doi.org/10.1016/j.nut.2017.08.001CrossRefPubMed

27.

Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B et al (2011) Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472:57–63. https://doi.org/10.1038/nature09922CrossRefPubMedPubMedCentral

28.

Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X et al (2013) Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med 368:1575–1584. https://doi.org/10.1056/NEJMoa1109400CrossRefPubMedPubMedCentral

29.

Velasquez MT, Ramezani A, Manal A, Raj DS (2016) Trimethylamine N-Oxide: the good, the bad and the unknown. Toxins (Basel) 8:326. https://doi.org/10.3390/toxins8110326CrossRef

30.

Nongpiur ME, Wong TY, Sabanayagam C, Lim SC, Tai ES, Aung T (2010) Chronic kidney disease and intraocular pressure: the Singapore Malay Eye Study. Ophthalmology 117:477–483. https://doi.org/10.1016/j.ophtha.2009.07.029CrossRefPubMed

31.

Shim SH, Sung KC, Kim JM, Lee MY, Won YS, Kim JH et al (2016) Association between Renal Function and Open-Angle Glaucoma: The Korea National Health and Nutrition Examination Survey 2010–2011. Ophthalmology 123:1981–1988. https://doi.org/10.1016/j.ophtha.2016.06.022CrossRefPubMed

Title: Glaucoma patients have an increased level of trimethylamine, a toxic product of gut bacteria, in the aqueous humor: a pilot study
Authors: Janusz Skrzypecki
J. Izdebska
A. Kamińska
J. Badowska
J. Przybek-Skrzypecka
J. Bombuy
E. Samborowska
J. P. Szaflik
Publication date: 01-01-2021
Publisher: Springer Netherlands
Keywords: Glaucoma
Cataract
Published in: International Ophthalmology / Issue 1/2021
Print ISSN: 0165-5701
Electronic ISSN: 1573-2630
DOI: https://doi.org/10.1007/s10792-020-01587-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Glaucoma patients have an increased level of trimethylamine, a toxic product of gut bacteria, in the aqueous humor: a pilot study

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2021

Real-world evaluation of visual results and patient satisfaction for extended range of focus intraocular lenses compared to trifocal lenses

Bacterial agents and changes in drug susceptibilities in cases of chronic dacryocystitis, Southern China

Correction of pseudophakic presbyopia using Lasik with aspheric ablation profiles and a micro-monovision protocol

Is optical coherence tomography angiography a useful tool in the screening of hydroxychloroquine retinopathy?

Intrastromal implantation of chicken corneal grafts into the cornea of rabbits for corneal thickening: an experimental study

Molecular and clinical characterization of Thai patients with achromatopsia: identification of three novel disease-associated variants in the CNGA3 and CNGB3 genes