Dr. Patrick: You brought up a question... I wanted to circle back to dietary composition because you've done so much work on that but what you just said brought up a question in my mind about cholesterol, the microbiome having an independent effect on cholesterol. We do know that genetics plays a role as well. Have you or any of your colleagues looked into the mechanism for that or multiple...I guess probably multiple mechanisms? I'm kind of thinking along the lines of even just inflammation and how, you know, when there's an inflammatory response, you know, cholesterol is kind of produced. Like that's kind of a well-known thing is that you should always have at least an "N of two" when you're getting your cholesterol levels measured because, you know, if you have some sort of stressful event or something that's causing inflammation or if you're sick, you can have, you know, high cholesterol levels. And that's not necessarily indicative of what your cholesterol levels are.

Dr. Elinav: You're absolutely right. And I can tell you that we and several other groups have reproducibly found that different aspects of healthy cholesterol and fatty acid metabolism in humans and in mice are modulated by the gut microbiome. So, for example, in the Personalized Nutrition Project and in interventional trials that were followed as part of this project, we found that modification of the personalized nutritional recommendations could lead to an improvement in HDL cholesterol, the good cholesterol.

Another group from the UK conducted a very ambitious follow-up trial similar to the Personalized Nutrition Project which we started with called the PREDICT Trial, and in this trial, they could show something very exciting, which is that the microbiome and the host could be used to predict a person's triglyceride levels. In other words, not only did they associate the microbes to features of fatty acid metabolism or triglycerides, which are one of the risk factors for cardiovascular disease, they could use data coming from the microbiome in order to predict a person's levels of triglycerides, which provides another stronger proof to the possible causal association between the two features.

Dr. Patrick: Do you think that some of the confounding factors in the many, many studies that have been done, for example, on saturated fat and, you know, the role of saturated fat in cardiovascular disease risk or in certain biomarkers that indicate cardiovascular disease risk like high cholesterol, LDL cholesterol, for example...? There's conflicting data where it's not always bad, but it does seem to be bad. So is there a microbiome component like in the way your body responds to saturated fat?

Dr. Elinav: I think that, you know, the specific answer is I don't know, but the conceptual answer is that in every study that we look or conduct, we find that inter-individual differences in the microbiome could play a role and potentially explain variabilities between studies in their outcomes even if they seemingly do the same thing and reach different conclusion. And I can give you endless examples. For example, our own studies on non-nutritive sweeteners or artificial sweeteners suggested that the microbiome is a very major player that modifies the response of some people but not of other people into some of the nutrients. And if you look at the body of evidence suggesting that nutrients adversely or favorably impact the human body, you know, it's all over the place, and the results are very conflicting with each other, and people, you know, spend their career fighting with each other, while some of the explanations could lie within inter-individual variabilities in their physiology including ones that are related to their microbiome.