B (3:24)

Iran, I'd love to switch to your research now. Very few people are actually doing studies on the microbiome in human beings where they're able to really understand specific impact of specific food. That's obviously something that is really fascinating to me and I think lots of listeners. Could you tell us, you know, I think you start, you're saying you started with this idea that these artificial sweeteners were inert. They didn't have any impact on us. What has your research shown?

C (3:51)

We started in exploring the possible impacts of these compounds of these sweeteners in animal models, specifically in mice, which are very controlled settings that we can learn a lot from, that they're not as complex as human beings and as diverse. My graduate student, now an independent researchers researcher in his own right at Hopkins in the US Designed an initial experiment in which he gave high doses of some of these compounds into mice that have never, of course, seen these compounds. And to our astonishment, his results were that these mice were developing a higher tendency to develop disturbances in their blood sugar control. They were kind of leaning towards the development of diabetes. He showed me these results. I did not believe them. Of course, being a skeptic scientist. He repeated them again and again and again. And this was very, very reproducible. And this was the first eureka moment which told us that something in the body of these mammals, of these mice, was actually reacting to these seemingly inert compounds in ways which could be detrimental to health. And this started a very long journey in which we at the beginning mainly focused on one of these compounds, which is called saccharine. It's the granddaddy of all artificial sweeteners. It's actually very popular as a sweetener in Israel, where we perform sacred studies. And we really dove deep into this one compound, tested it in different doses, including doses that are equivalent to the lower doses that humans consume, different mice, different genders, and so on and so forth. In all of these cases, we found that in mice housed in our facility that carry a specific microbiome, the consumption of saccharine was associated with a quite remarkable tendency to develop disturbances in sugar control, to develop diabetes.

B (5:59)

You're saying that you took these mice, you were just giving them this artificial sweetener, you weren't giving them any, like, sugar or doing anything else that was changing their diet. You were just giving this artificial sweetener, which, you know, we've all been told doesn't do anything in our body, tastes sweet, goes through. And in these mice, you actually ended up giving them diabetes, which is a disease that I associate with having lots and lots of sugar and other sweet food. Is that right?

C (6:23)

Yeah, that's, that's absolutely right. And, and, and this occurred, you know, when we gave these, these mice different diets, for example, a diet reminiscent of, of the western diet, full of, of fat or in, in healthier diets. And, and this, this seemed to be at least in our facility. And the question was, since this compound has been known and studied for a century, and we know that the, the, the mammalian cells, the mouse cells and the human cells and probably don't digest it, how do the consumption of this compound resulting in these diabetic effect? And this is where the microbiome came in. And we started looking into the microbiome because this is what we do in life. And we found to our surprise, that the microbes were actually reacting to this compound. And we could even induce diabetes. By taking the microbes from the guts of mice that were consuming sacchari and transferring just the microbes into mice that have never seen saccharine. These recipient mice developed diabetes, proving that the microbiome was actually driving the effect. This was a very big eureka moment for us, leading to the publication of our findings in Nature in 2014. And as you can imagine, this generated a lot of discussion that span outside of the scientific and medical communities. And one must also mention that in this initial study, we've also performed a very small preliminary study in human volunteers who were given saccharine. And we found that half the people who were exposed to saccharine didn't care at all. They didn't change their blood sugar control. Their blood sugar levels were completely the same. But the other half of these individuals develop marked disturbances in their blood sugar control. Even after a week of exposure to this compound. None of the individuals in this small preliminary trial actually improved their blood sugar control. This was a very counterintuitive, but a very important moment in this type of study because it told us something very fundamental, not only about artificial sweetness. It told us that rather than quantifying foods or food components in their ability to induce changes in the human body or in the mouse body in this case, we need to start thinking about how to quantify the recipient, the people who actually consume these compounds. And this goes against the one size fits all dietary paradigm that was prevalent for 50 years before this and led to the personalized nutrition concept which was developed. And artificial sweeteners in our hands were the very first example of these personalized microbiome driven effects that dictate why one person would react to a given food while the other person would not react to the same exact food, even when it's consumed at exactly the same quantities.

B (9:31)

So imagine that you're saying that both Coca Cola and our diet Coca Cola is off the table and same for all the other manufacturers, but there'll be a lot of people saying, well, it's like really hard to switch from that to water because I'm really used to all of these sweet tastes. Do you have like an easy tip for how to transition off those drinks for anyone who's listening?

D (9:52)

Well, it's, most of us have done this when we were kids. We used to, I used to anyway have tea with about four spoons of sugar in it when I first started having it. And gradually you just dial it down so that you can go to three and then to two and then to one. And I think the same is true with these products. You need to wean yourself off, I think that amount of sugar. And once you've done that, they're too sweet for me to actually have them. Now we do have these thresholds for sweetness that we can manipulate ourselves and getting used to more bitter tastes and sour tastes and fermented drinks and things like this are an important way. So I think teas, kombuchas, and diluting down these products gradually to get yourself off them in a few months is probably the way to do it.

A (10:48)

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