In this study led by Janusz Skrzypecki at the Institute of Biochemistry and Biophysics in 2020, the researchers found that trimethylamine (TMA), a gut bacteria metabolite, was present in the aqueous humor (the clear fluid filling the space in the front of the eyeball between the lens and the cornea) of patients with glaucoma.
Moreover, the study revealed that the level of TMA in the aqueous humor of patients with advanced open-angle glaucoma was significantly higher than in a control group of patients undergoing phacoemulsification (a type of cataract surgery).
The elevated levels of TMA in the aqueous humor of glaucoma patients, as revealed by this study, strike me as a very interesting finding. Importantly, the levels of TMA, which can have various health impacts beyond glaucoma, can be influenced by diet and other lifestyle factors.
The study detected TMA, betaine and trimethylamine N-oxide (TMAO) in the aqueous humor. Betaine, TMA, and TMAO are related metabolites; TMA is metabolized by gut bacteria and is subsequently converted to TMAO in the liver. However, in the context of glaucoma, only the levels of TMA were found to be increased, not those of betaine or TMAO.
The authors share their views on the significance of this finding:
We believe that TMA and TMAO might constitute a common humoral background which affects not only cardiovascular system, but also has a direct or indirect effect on the structure of the optic nerve. Firstly, TMA and TMAO are involved in blood pressure (BP) homeostasis. Notably, dysregulation of BP is considered a risk factor for both cardiovascular mortality and glaucoma. Secondly, TMAO was shown to accelerate development of atherosclerosis which is considered a risk factor for glaucoma.
However, [a] growing body of research shows that it is not TMAO ... but rather TMA itself is toxic...
The researchers mention that a landmark study which linked an increased level of TMAO to cardiovascular mortality triggered their interest in this topic. It is also a topic I have been following for multiple years. Over time good evidence has continued to mount and there is no doubt that we need to be aware of TMA and TMAO now. However, there are still many gaps in our understanding.
This study particularly caught my attention because the gut microbiome is something we can modify via a healthy lifestyle. Other studies have also shown that we can impact our body's production of TMAO by dietary changes. Furthermore, the most recent studies prove that bacterial metabolites are involved in pathophysiology of many diseases. Whether or not TMA is eventually proven to be a causative factor in glaucoma, we can reduce our risk of multiple other serious health concerns by paying attention to our gut microbiome (such as through our food choices -- more on that below).
Trimethylamine (TMA) is a metabolite produced by the gut bacteria as they break down certain nutrients found in food, particularly choline, betaine, and carnitine, which are abundant in red meat, eggs, and some seafood. Consequently, the levels of TMA can be influenced by diet and other lifestyle factors.
Here are some ways lifestyle modifications can potentially improve TMA levels:
Dietary Changes: Certain dietary changes can lead to lower production of TMA by the gut bacteria. The consensus recommendations include limiting the consumption of red meat, eggs, and certain (but not all) types of seafood. Increasing the intake of fiber and plant-based foods is very beneficial, as they promote a healthier gut microbiome.
Probiotics: Consuming probiotics or fermented foods that contain beneficial bacteria can help in modulating the gut microbiota. Some studies have shown that people who consume a plant-based diet do not produce TMA even when they consume the foods that would normally result in TMA production.
Medications and Supplements: Certain medications or supplements might affect the gut microbiome or the production of TMA. For example, berberine has been shown to have a beneficial effect.
Physical Activity: Engaging in regular physical activity can have an impact on the gut microbiome and, in turn, might influence the production of TMA.
Maintaining a Healthy Weight: Obesity has been linked to alterations in the gut microbiome. Losing weight through diet and exercise might help restore a healthier balance of gut bacteria and potentially reduce TMA production.
Here's the study 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, the levels of betaine, TMA, and TMAO were 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.