 Metabolomics is a term used to describe the measurement of multiple metabolites in biological specimens like bodily fluids with a goal of identifying molecular signatures. For example, if you compare the metabolic profile of those with severe heart disease to those with clean arteries, maybe we could come up with a cheap, simple, non-invasive way to screen people. If heart patients happen to have something in their blood that healthy people didn't, we could test for that. And maybe it would even help us understand the mechanisms of disease. To refer to metabolomics as a new field, though, is to do injustice to ancient doctors who used ants to diagnose people with diabetes, because the ants could detect the sugar in their urine. The first modern foray discovered hundreds of substances in a single breath, for example, thanks to the development of computer technology that made it possible to handle large amounts of information. And that was in 1971, a time when computers looked like this. New technologies have allowed researchers to measure hundreds, or even thousands of metabolites at a time, which is good, since more than 25,000 compounds may be entering our body through our diet alone. The data comes out looking like this, which computers can turn into maps that allow researchers to try to piece together connections. Metabolomics is where the story of TMAO started. Everyone knows that a bad diet can lead to heart disease, but which dietary components are the most harmful? So researchers at the Cleveland Clinic screened blood from patients who had experienced a heart attack or stroke, and compared the results with those from blood of people who had not, using all sorts of fancy technology, they identified a compound called TMAO, which stands for trimethylamine oxide. The more this TMAO stuff people had in their blood, the greater the odds they had heart disease, and the worse their heart disease was. Where does this TMAO stuff come from? Our liver turns TMA into TMAO. Okay, where does TMA come from? Certain bacteria in our gut turn something in our diet called choline into TMA. Where is the highest concentration of choline found? Eggs, milk, and meats, including poultry and fish. So when we eat these foods, our gut bacteria may make TMA, which is absorbed into our system and oxidized by our liver into TMAO, which may then increase our risk of heart attack, stroke, and death. But just because at a snapshot in time, people with heart disease tend to have higher TMAO levels, doesn't mean having high TMAO necessarily leads to bad outcomes. We'd really want to follow people over time, which is what they did next. 4,000 people fall for three years, and those with the highest TMAO levels went on to have significantly more heart attacks, stroke, or death. Wait a second, though. If high TMAO levels come from eating lots of meat, dairy, and eggs, then maybe the only reason people with high TMAO levels have lots of heart attacks is they're eating lots of meat, dairy, and eggs. Maybe having high TMAO levels is just a marker of a diet high in red meat, eggs, milk, and chicken that's killing people by raising cholesterol levels or something, and has nothing to do with TMAO at all. Conversely, the reason a low TMAO level seems so protective may just because it's indicative of a more plant-based diet. One of the reasons we think TMAO is directly responsible is that TMAO levels predict the risk of heart attack, stroke, and death independently of other traditional cardiovascular risk factors, meaning whether or not you have high cholesterol or low cholesterol, high blood pressure, or low blood pressure, having high TMAO levels appear to be bad news. This has since been replicated in other states. Up to 9 times the odds of heart disease at high TMAO blood levels, even after controlling from meat, fish, and cholesterol intake, which is a surrogate for egg intake. But what about the rest of this sequence? How can we be certain that our gut bacteria can take the choline we eat and turn it into trimethylamine in the first place? Easily, they just have to administer a simple dietary choline challenge. How do you do that? Just give them some eggs. Have people eat two hard-boiled eggs and you get a bump of TMAO in their blood within an hour of consumption. Ah, but what if you gave them antibiotics to wipe out their gut flora? Then you can give them eggs and nothing happens. In fact, their TMAO levels are down at zero, showing gut bacteria play a critical role. But if you wait a month to give their gut some time to recover from the antibiotics, TMAO levels come creeping back up. These findings did not thrill the egg industry. Imagine you work for the American Egg Board, tasked with designing a study to show no effect of eating nearly an egg a day. How could you rig it to show no difference? Well, if you look at the effect of an egg meal, you get a bump in TMAO levels, but your kidneys are so good at getting rid of this nasty stuff that by hours 4, 6, 8, you're back to baseline. So all you have to do is just make sure they hadn't eaten those eggs in the last 12 hours, and you can show no effect and get your study published in the Journal of the Academy of Nutrition and Dietetics, and collect your paycheck.