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

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

doi:10.1007/s10792-020-01587-y

Abstract

PurposeAnimal 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.MethodsTwenty 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.ResultsIn 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.ConclusionTMA, 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.

Highlights

The most recent studies prove that bacterial metabolites are involved in pathophysiology of many diseases [1]
Considering that level of TMA was shown to be inversely proportional to estimated glomerular filtration rate [10], whereas level of trimethylamine N-oxide (TMAO) correlates with cardiovascular mortality; we decided to match patients on eGFR as well as diseases related to cardiovascular mortality, i.e., diabetes, hypertension and ischemic heart disease
We have found that the aqueous humor contains TMA, a gut bacteria metabolite, as well as a substrate and a product of its metabolic pathway, i.e., betaine and TMAO, respectively

Summary

Introduction

The most recent studies prove that bacterial metabolites are involved in pathophysiology of many diseases [1]. Their role in multiple sclerosis, hypertension, heart failure or cancer has been highlighted [2]. Recent evidence implies that gut bacterial metabolites, including short-chain fatty acids (SCFA), hydrogen sulfide and trimethylamine N-oxide (TMAO), play an important role in regulation of intraocular pressure (IOP) [3,4,5]. TMAO protects cardiomyocytes from increased load in the setting of hypertension or heart failure in rats and acts as a buffer against increased osmotic and hydrostatic pressure in the deep-sea animals [6,7,8]. Trimethylamine (TMA), a substrate for TMAO synthesis, exerts cytotoxic effect on vascular smooth muscles and cardiomyocytes [9, 10]

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