What we eat plays an important role in our health and directly affects key health markers linked to our wellbeing including lipid profile, blood sugar, and blood pressure. More importantly, foods can alter gut microbial biodiversity, which may lead to the production of harmful byproducts. Recent studies indicate diets high in red meat, egg yolk, and dairy products lead to increased concentrations of trimethylamine oxide (TMAO) and phenylacetylglutamine (PAGln). These compounds can lead to an increased chance of developing cardiovascular disease due to arterial plaque deposits.

Research conducted by the Cleveland Heart Lab shows an elevated risk of developing cardiovascular disease when levels of TMAO increase in the body. This is caused by consuming foods with high amounts of choline and L-carnitine. In turn, the gut microbiome then produces high concentrations of TMAO. (1) In a recent study using a group of 2,225 patients with coronary artery disease, researchers found patients with elevated TMAO levels were four times more likely to experience premature death compared to those containing normal TMAO levels. (1)

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"Researchers found patients with elevated TMAO levels were four times more likely to experience premature death compared to those containing normal TMAO levels."

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Another gut byproduct biomarker shown to present adverse effects in cardiovascular health is phenylacetylglutamine (PAGln). In a study conducted by Romano et al., researchers looked at correlating concentrations of PAGln and heart failure. In this study, researchers measured PAGln, left ventricular ejection fraction, and N-terminal pro-B-type natriuretic peptide in 4,085 patients in an attempt to associate high levels of these biomarkers with heart failure. (2) What they found was elevated levels of PAGIn and phenylacetlyglycine were closely associated with the phenotypes linked to heart failure. (2)

Consequently, the future of medicine may lie in controlling the gut microbiome and the metabolites they produce. In a recent interview, Dr. Hazen (MD, PhD, Chair of the Department of Cardiovascular and Metabolic Sciences at the Cleveland Clinic) said, “The gut microbiome is a new strategy in medicine.” Dr. Hazen continued by saying his team has already developed drugs to block TMAO generation, which are showing benefits to patients with cardiovascular disease in preclinical models.(3) Additionally, there is currently no compound for the inhibition of PAGIn.(3) Until that "magic pill" is developed, it is highly advisable to cut back, or even eliminate, animal products from one's diet in order to reduce the concentration of these highly inflammatory substances that are exacerbating atherosclerosis and heart disease.

Due to the biodiversity of each individual’s microbiome, more research is needed to definitively correlate microbiological metabolites to disease. There is a growing amount of data to support the effects of TMAO and PAGln; however, more research is required to find other hazardous metabolites and their interactions. Research into human health and the microbiome is a promising start to a future of personalized medicine that may be able to eliminate diseases by balancing gut dysbiosis.

By Miles Amby

R&D Microbiologist - Hardy Diagnostics

Works Cited: 1, 2, 3

Outbreak of extensively drug-resistant Pseudomonas aeruginosa associated with artificial tears

Eye drops are a common household item used to relieve the symptoms of dry eyes. Just as common is Pseudomonas aeruginosa, a bacteria found in the environment such as soil and water. What ties these two common entities together? A multistate outbreak of a rare strain of extensively drug-resistant Pseudomonas aeruginosa, which is suspected to be linked to specific brand of eye drops.

Multi-drug resistant (MDR) Pseudomonas aeruginosa is a growing threat in the United States and globally. In 2017, the CDC reported an estimated 32,600 infections among hospitalized patients and an estimated 2,700 deaths in the U.S. (1) These infections are among the most common to occur in healthcare settings, especially in patients with catheters, who are on ventilators, or who have open wounds. (1)

The strain involved in the most recent outbreak, carbapenem-resistant Pseudomonas aeruginosa with Verona integron-mediated metallo-β-lactamase and Guiana extended-spectrum-β-lactamase (VIM-GES-CRPA), had never been reported in the United States prior to this outbreak. (2) Additionally, it has been characterized as extensively drug-resistant (XDR), showing resistance to over ten antimicrobial agents. (2) A badly infected eye with Pseudomonas is shown below.

As of February 2, 2023, CDC had identified 58 patients across 13 different states with VIM-GES-CRPA who has used artificial tears. (2) While this outbreak is associated with multiple types of infections, eye infection appears to be the most common. Symptoms may include eye pain, redness of the eye, increased sensitivity to light, blurry vision, or an unusual discharge from the eye.(3) There have been five reports of vision loss and one person has died from a blood stream infection. (2)

In order to determine the best treatment options, healthcare providers are encouraged to consult with a specialist knowledgeable in the treatment of antibiotic-resistant bacteria. (2) Additionally, XDR Pseudomonas aeruginosa has the potential to spread rapidly in healthcare settings; therefore, infected patients should be placed in isolation and all infection control recommendations should be closely followed. (2)

In surveying patients, CDC found that the common denominator was usually EzriCare Artificial Tears, a brand of preservative-free eye drops. Testing confirmed the presence of VIM-GES-CRPA in the patients’ opened EzriCare bottles. (3) CDC is further investigating by testing unopened bottles to determine if the bacteria was introduced during the manufacturing process. (4)

The manufacturer, Global Pharma Healthcare, has initiated a voluntary recall of EzriCare and Delsam Pharma’s Artificial Tears as recommended by the FDA. The FDA reported the company is in violation of Current Good Manufacturing Practice (cGMP) regulations. (5) These products lack appropriate microbial testing, are not made with an adequate preservative to prevent contamination, and are absent of a tamper-proof seal. (5) Consumers who still own this product are urged to stop use immediately and see a doctor if any symptoms occur. (4)

As this outbreak demonstrates, MDR and XDR Pseudomonas aeruginosa can cause severe bacterial disease that can be difficult to treat as antimicrobial resistance increases. Drug manufacturers' compliance with cGMP, preservative efficacy testing (PET), continued infection control, and proper use of antibiotics is needed to help prevent the spread of multi and extensively drug-resistant organisms in consumer products, healthcare settings, and beyond.

References: 1, 2, 3, 4, 5

By Allie Malmberg

Technical Services Supervisor - Hardy Diagnostics