Gut microbiome linked to dietary compound found in heart disease
Findings from a Cornell University study, which appear in the journal Molecular Nutrition and Food Research, found that compared to eggs and beef, eating fish resulted in increased levels of circulating trimethylamine N-oxide (TMAO).
High levels of TMAO are naturally found in fish and in humans the gut bacteria firmicutes, aids in convert the nutrient choline (from eggs) and carnitine (from meat) into TMAO.
It was found that higher levels of firmicutes compared to another bacterial species bacteroidetes in some individuals resulted in greater TMAO production and subsequent levels - a known predictive risk factor for heart disease in cardiac patients.
The results raise a host of questions, one of which asks whether the gut microbiome is playing a role in the disease process rather than the TMAO itself.
"My hypothesis is that diseased individuals - whether it's heart disease, cancer or other chronic diseases - are going to have a different microbiome than non-diseased individuals,” said Dr Marie Caudill, Cornell professor of nutritional sciences and lead author of the study. “The microbiome can be marked by TMAO levels in the blood."
Another question involves the role of TMAO and whether it causes heart disease or is simply a sign of the disease’s progression.
Study design
The team employed a randomised, controlled crossover design, where 40 healthy men aged 21–50 years with a BMI of 20–29.9 kg/m2 were recruited. Blood and urine samples were obtained at the start of the study.
Participants then consumed four different study meals. These meals were (1) three eggs, (2) six ounces of beef, (3) six ounces of fish (cod) and (4) a control meal of fruit. Each of these meals was administered in random order in a single day separated by a one-week period.
Following the consumption of the study meal, blood samples were obtained again, this time at 15 and 30 minutes, and one, two, four, and six hours and each participant provided urine samples throughout the six hour study period. These were carried out in order to measure TMAO levels.
At 4.5 hours the men ate a fixed snack of apple sauce and water. Throughout each study session, participants refrained from eating and drinking foods and beverages (other than water) outside those provided by the study.
Results showed that fish produced a higher circulating and urinary TMAO concentration (46–62 times) when compared to eggs, beef, or the fruit control.
Circulating TMAO concentrations were elevated after 15 minutes of fish consumption, indicating that dietary TMAO could be absorbed without processing by gut microbes.
Analysis of the subject’s genes showed that high-TMAO producers (more than a 20% increase in urinary TMAO after eating eggs and beef) had more Firmicutes than Bacteroidetes and less gut microbiota diversity.
"This provides some evidence that the elevation in TMAO may simply be a biomarker of differences in the gut microbiome," said Caudill.
“It is very likely that our diets interact with our gut microbiome to influence disease risk, and that our diet influences our gut microbiome composition,” she added.
Dietary changes needed?
Recent research has identified TMAO as a predictive risk factor for heart disease in cardiac patients and colorectal cancer among postmenopausal women.
The effects of animal source foods on TMAO generation, absorption, and elimination in healthy adults, however has suffered from a lack of attention.
The study concluded that recent studies proposing TMAO as a causative agent for cardiovascular disease, could give reason for some to advise on the restriction of animal source foods that raise circulating TMAO concentrations. However, Caudill remained cautious.
“Unless it is demonstrated that TMAO is a causative agent in the disease process, eating fish in recommended quantities does not need to be re-examined,” she said. “Likewise, people should not be restricting consumption of foods such as eggs and meat because of their TMAO raising properties.”
“It seems prudent at this time to place the emphasis on a high quality plant based diet that incorporates lean sources of meat (and eggs) to meet nutritional requirements.”
Source: Molecular Nutrition and Food Research
Published online ahead of print, DOI 10.1002/mnfr.201600324
“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.”
Authors: Marie Caudill et al.
