The Problem

Acetaldehyde is an unwanted molecule that can build up in the body when drinking alcohol

Here’s the problem. The body has many biological reactions to drinking alcohol, not all of which are pleasant. The metabolism of alcohol produces a variety of small molecules and cellular responses which, when piled-up, can be hard on your body and throw you off your healthy routine. One of those small molecules is acetaldehyde, an unwanted, toxic byproduct of alcohol metabolism. Its chemical structure is highly reactive, which means it can interact with a whole host of molecular and cellular components throughout our bodies. But how does alcohol become acetaldehyde?

The Solution

The liver can fully metabolize acetaldehyde, but the gut isn’t properly equipped to do the same

When you drink, most of the alcohol you consume gets digested in the liver using a two-step process (see diagram). Each step requires a different enzyme produce by your liver.

  1. Alcohol dehydrogenase (ADH) converts ethanol into acetaldehyde by removing hydrogen atoms—a process called oxidation.
  2. Acetaldehyde dehydrogenase (ALDH) then further oxidizes acetaldehyde into acetate by adding an oxygen atom, producing a more stable and innocuous compound.

However, some of the alcohol you drink never reaches your liver. Instead, it is metabolized in your gut, in large part by the microbes that reside there. Some microbes in the gut microbiome are equipped with the first enzyme, ADH, and can convert alcohol into acetaldehyde. But in contrast to your liver, they don’t make enough of the second enzyme, ALDH, to convert acetaldehyde into acetate. This is the major cause of acetaldehyde buildup in your body (Salaspuro, 1996).

Thus arises a clear hypothesis: If we can equip the gut microbiome to break down acetaldehyde into acetate, we can support the body’s ability to minimize the buildup of this toxic byproduct. While the liver is fully capable of metabolizing acetaldehyde, the gut is not—and that gap makes this approach especially valuable for those planning to have a drink or two.

Data & Validation

Our engineered probiotic has been tested in the lab for safety and functionality

Once ZB183™ was built, we needed to ensure that it was safe, and that it worked as intended.

Safety

We subjected ZB183™ to years of laboratory testing and review by America’s top food toxicologists, the results of which confirmed it to be completely safe and FDA-compliant. The data from these tests has been published in the peer-reviewed Journal of Toxicology.

Now that we have confirmed our genetically engineered probiotic is safe and works as intended, we make sure this is true of every batch. Pre-Alcohol undergoes rigorous quality testing at every stage, from probiotic biomass to the final product, ensuring safety, purity, and efficacy. We transparently publish our standards for each test on our Quality page which can be found here.

Functionality

To confirm that ZB183™ worked as intended, we tested its ability to make ALDH and break down acetaldehyde. Over a series of laboratory tests where we compared it to the unedited B. subtilis strain, we confirmed that our Pre-Alcohol Probiotic was highly effective at producing ALDH. We also confirmed that while the control strain broke down almost no acetaldehyde, ZB183™ was able to break down more acetaldehyde than you could ever encounter when drinking. We published a paper containing the data from these tests, and it can be found in the peer-reviewed PLOS One journal..

As scientists we appreciate that every body is different and so there are no silver bullets in biology. Even though we’ve proven that the product can reliably provide the function of helping to metabolize acetaldehyde, we don’t know for sure that it will be perceived as valuable for everyone. However, we do know from customer use data that it does appear to provide a benefit to the vast majority of users (i.e. >95%). And with millions of bottles sold, that’s a lot of happy customers!

ZB183™ was our first proof of concept on a bigger journey to unlock the immense potential of safely and consciously-built genetically engineered microbes.

When you're drinking. The earlier the better.

When do I drink Pre-Alcohol?

How long does 1 bottle of Pre-Alcohol last after I drink it?

Is Pre-Alcohol FDA-compliant?

Does Pre-Alcohol affect my level of intoxication?

Will Pre-Alcohol change my microbiome?

We need more fiber

Fiber plays an important role in our health, but most of us aren’t getting enough fiber in our modern diets. We need 25-30 grams of fiber per day, but about 95% of us don’t meet that goal (citation). There are likely a few reasons why we don’t get enough fiber, and they vary from person to person. One big factor is the overall fiber content of many of the foods we consume. Processed foods (think white bread, pasta, etc.) are often convenient and accessible, but they tend to use refined grains,  which have far less fiber than their whole-grain counterparts. It’s also not just about eating healthier. If you steer clear of processed foods you are likely still at risk of not meeting your daily fiber needs. It may seem obvious that ultra processed foods tend to be low in dietary fiber, but did you know that popular, seemingly healthy food trends also make it difficult to get enough fiber in your diet? Notably, carb-reducing, gluten-free and keto diets are notorious for low fiber intake. Regardless of what you eat, it’s unlikely that any of us will meet the recommended daily dose of fiber. It takes a true concerted effort to include fiber rich foods in our diets.

We need more diverse fibers

The story isn’t just about more fiber. There are actually many different types of dietary fibers that provide varying health benefits. Important characteristics include whether or not a fiber is soluble and whether or not a fiber is fermentable. When a fiber is insoluble (does not dissolve in water) it acts as a bulking agent, speeding up the rate of digestion, whereas a soluble fiber tends to dissolve into a gel-like substance that actually slows down the rate of digestion. Insoluble fibers play a role in bowel regularity and easing constipation, while soluble fibers provide benefits such as increased nutrient absorption and lowered cholesterol. Soluble fibers can also be fermentable, meaning that they feed the gut microbiome, a complex ecosystem of microbes that impact everything from our gastrointestinal health to our mental health. We also call fermentable fibers ‘prebiotics’ because they support a healthy and balanced gut microbiome. 

It’s clear that there are many benefits to fibers in our diet, so when we say we aren’t getting enough it means two things: 

  1. We need more total fiber.
  2. We need more fiber diversity.

While it takes effort to get more fiber in our diet, it takes even more effort to make sure we get a diversity of fiber types.

We eat plenty of sugar but not enough fiber

While we don’t get enough fiber, the modern diet tends to provide us with an excess of sugar. So what if we use that sugar to make more fiber? Because fiber molecules are just long chains of sugar, that’s easier to do than you’d think! Chemically speaking, sugars and fibers are both carbohydrates—also known as saccharides. The difference between them is how many molecular building blocks make up the final product. Sugars are either a single building block (monosaccharide) or 2 building blocks linked together (disaccharides). Table sugar (sucrose)—the sugar found in your pantry and in many of the fruits, vegetables, and nuts we consume—is a disaccharide. It is made up of 2 building blocks: 1 glucose and 1 fructose. Fibers, on the other hand, are made up of 10 or more molecules (polysaccharides). For example, cellulose—the fiber found in leafy greens—is made up of many individual glucose molecules chained together. 

Our scientists understood that the building blocks of sugar and the building blocks of fiber are the same. So we asked ourselves, “Is there a way to convert some of the sugar we consume into the fiber that we need?” The answer we came up with is the unique ingredient in Sugar-to-Fiber: our proprietary probiotic, Bacillus subtilis ZB423™ (“ZB423™).

Introducing Bacillus subtilis ZB423™, the key ingredient in Sugar-to-Fiber

Using genetic engineering, our team of PhD microbiologists took a normal probiotic bacteria you likely eat every day (the species Bacillus subtilis) and engineered it to convert sugar into fiber steadily throughout the day. The resulting probiotic bacteria is ZB423™.

The DNA we introduced into ZB423™ enables this unique probiotic to produce levansucrase, a functional molecule (enzyme) that can do two important actions:

  1. Break apart table sugar (sucrose) into its molecular building blocks (glucose and fructose)
  2. Reroute the fructose and use it to build a rare fiber called levan.

The production of levansucrase by ZB423™ literally turns sugar (sucrose) into fiber (levan). And just like our Pre-Alcohol probiotic (ZB183™), this engineered bacteria can deliver that particularly useful enzyme directly to where it is needed most: the gut. Also, by using a probiotic,  we enable the conversion of sugar into fiber slowly throughout the day. This maximizes the benefit in the body and delivers the fiber in a way that your microbiome prefers, rather than all at once.

  1. Break apart table sugar (sucrose) into its individual sugars (glucose and fructose)
  2. Reroute the fructose and use it to build a rare fiber called levan.

This probiotic is engineered to literally turn sugar (sucrose) into fiber (levan). As with our Pre-Alcohol probiotic, we engineered a bacteria to deliver an enzyme directly to where it is needed most. Also - by using a probiotic bacteria to deliver levansucrase, it can convert sugar into fiber slowly throughout the day. This maximizes the benefit in the body and delivers the fiber in a way that your microbiome prefers. 

Sugar-to-Fiber is engineered to make a rare, prebiotic fiber called levan

As mentioned above, the levansucrase builds a fiber called levan. Levan is a fructan, which means it is a fiber made up of fructose molecules. So when we say it reroutes fructose, that is because it can literally pull fructose away from sucrose and chain it with other fructose molecules until they build a fiber. 

But why levan? First of all, this fiber is highly fermentable, so it can be used as food for the other microbes in your gut. This makes levan a prebiotic— able to support a healthy gut microbiome. Second, levan is a soluble fiber, and we know soluble fibers support our overall health. Third, levan is not very accessible in a Western diet. It is more common in other countries like Japan where dishes like natto (fermented soybeans) are a good source of levan. Because we don’t consume much of it, adding a source of levan production to your gut inherently increases the diversity of fiber you are consuming. When we consume diverse fermentable fibers, we also encourage a diverse or balanced gut microbiome! You can read more about that in our previous blog article, where we explain the importance of supporting the gut microbiome with a diversity of fibers.

The Result: your body gets more of what it needs and less of what it doesn’t, creating a path to gut health from the foods you already eat that wasn’t possible before Sugar-to-Fiber.

Our engineered probiotic has been tested in the lab for safety and functionality

As with our Pre-Alcohol probiotic ZB183™, once ZB423™ was built, we needed to ensure that it was safe and that it worked as intended.

Safety

We subjected ZB423™ to years of laboratory testing and review by America’s top food toxicologists, the results of which confirmed it to be completely safe and FDA-compliant. The data from these tests has been published in the peer-reviewed Journal of Applied Toxicology.

Now that we have confirmed our genetically engineered probiotic is safe and works as intended, we make sure this is true of every batch. Sugar-to-Fiber undergoes rigorous quality testing at every stage, from probiotic biomass to the final product, ensuring safety, purity, and efficacy. We transparently publish our standards for each test on our Quality page which can be found here.

Functionality

To confirm that ZB423™ worked as intended, we tested its ability to make levansucrase, break down sucrose, and produce levan. Over a series of laboratory tests where we compared it to the unedited B. subtilis strain, we confirmed that ZB423™ was highly effective at breaking down sucrose using expressed levansucrase and converting the fructose molecules into levan fiber.  

One of the tests we ran was our levansucrase activity assay, which mixes sucrose and ZB423™ to show the activity of ZB423™-produced levansucrase. You can see that after twenty minutes there is a significant decrease in sucrose, combined with an increase in free glucose. As a reminder, the levansucrase enzyme cleaves sucrose into glucose and fructose, and then stacks the fructoses together to make levan fiber. This leaves the glucose free. To quantify the activity of the enzyme, we measure the amount of free glucose released over time after inputting a known quantity of sucrose. This free glucose is therefore a proxy for measuring levan fiber production.

As scientists we appreciate that every body is different and science is not one-size-fits-all. Even though we’ve proven that the product can reliably express the enzyme that converts sugar into fiber, that’s just the start. Over the ensuing months we will be publishing more data on how Sugar-to-Fiber works, hoping to share, to educate, and not to overwhelm. In the meantime, we thank you. By using Sugar-to-Fiber, you’re at the forefront of GMO technology, experiencing the benefits of cutting-edge science for yourself.

The road ahead

As we continue to explore the challenges of modern life, it’s clearer to us now more than ever that there is real need for a new generation of probiotics—built with purpose, based in science. And at ZBiotics, we are dedicated to bringing that next generation to you, and providing the information you need to decide whether you’d like to choose any of them to incorporate into your life.

Now for the first time ever, by adding Sugar-to-Fiber to our lineup you have more than one choice. There are now TWO genetically engineered probiotics on the market. So whether you already love us for Pre-Alcohol or you are trying us out for the first time with Sugar-to-Fiber, we are so excited for you to join us.

Who are we? The very same people who did the research and built this technology: the ZBiotics team. We pride ourselves on the fact that we are a team founded and led with science at our core. Our technology is developed in-house by our own scientists in our own microbiology lab. This integrated approach allows us to create the best products available — products that marry cutting edge technology with innovative product design.

Our founder, CEO, and inventor of the primary technology underlying Pre-Alcohol is Dr. Zack Abbott. Zack’s background is as a microbiologist; he received his PhD in Microbiology & Immunology from the University of Michigan. After that, he worked designing clinical trials for biotechnology and pharmaceutical companies prior to starting ZBiotics to bring the idea of genetically engineered probiotics to the world.

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