Bacterium in the Gut Could be a Biomarker to Predict the Severity of COVID-19 Symptoms

Pharmacy Times is thrilled to welcome Sabine Hazan, MD, Founder and CEO of Progenabiome, which has trailblazed research looking at the gut microbiome and COVID-19. Hazan discusses the importance of a healthy gut, how the stool can predict disease, and how members of 1 family can suffer from COVID-19 with varying symptoms and severity.

Q: The gut microbiome is a hot conversation in health, but it can also be somewhat ambiguous. Can you describe the importance of the microbiome? (What are symptoms of imbalance?)

Sabine Hazan, MD, Founder and CEO of Progenabiome: that's actually a loaded question, but I'm going to try. So the gut microbiome is essentially all the microbes that live inside your bowels. When you look at this (and I hate to be graphic) but when you look at this log in the toilet, that's an accumulation of microbes. When you look at the dung of an elephant, for example, that's an accumulation of microbes. And those microbes are bacteria and viruses and fungi and parasites, it's everything in there.

Basically, that's what the microbiome is— the microbiome is an accumulation of microbes, that (when they are in balance) creates health, and when they are out of balance, creates disease. In other words, if you have done too much of something that killed your good microbes, then your good microbes are really low, and your bad microbes start taking on the space where the good microbes used to live. It's basically space that gets occupied by the bad.

I don't like to think of microbes as good or bad really, it is kind of equal. But sometimes, you know, one group overshadows another and it's really the imbalance. So, when there's an imbalance, people have unhealthy problems—and that can start with gastrointestinal (GI) problems. And as we're demonstrating with Progenabiome, it can go on to neurological problems that can go on to Lyme disease.

If you look at Parkinson's patients, for example, Parkinson's patients were constipated 10 years before the diagnosis of Parkinson's. They started an imbalance that basically started the ball rolling, the domino effect, of microbes that are basically continuing to become unadjusted (not equal, not in balanced) to create the disorder.

Q: How can stool be a determinate of health?

Sabine Hazan, MD: When we look at a stool sample, what people don't realize is we're looking at your genes, and your microbes—it's all in a stool sample. That's the future anyways, that we're going.

When you look at the data on Parkinson's, and you see that in Parkinson's, people took polyps 10 years prior to the diagnosis of the Parkinson's. Those polyps already had signs of Parkinson's in those people. They looked at polyps that were taken out of people that were constipated, and then looked at all those samples, and then went back and said, “Okay, let's look at to see if those people have Parkinson's.” 10 years later and sure enough, they have Parkinson's. So you can determine in your bowels (early on) that you are going to be predisposed to having Parkinson's in the future. That's the future we are going.

As already you're seeing it with stool samples that we're doing where we're looking for colon cancer. So you do a stool sample and it can predict whether you're going to have colon cancer or not. That is going to be the future—it is going to be a stool sample that is going to tell you whether you have something, or you're predisposed to something. That's what I'm working on anyways. And that's the research that I'm doing.

Q: Is there a relationship between COVID-19 and the gut microbiome?

Sabine Hazan, MD: I think when we look at COVID-19-19, when we look at (Helicobacter pylori) H. pylori, and when we look at bugs in general, they create diseases. In hepatitis C, we see the damages that have seeded on the liver. We saw the damages that H pylori did on the stomach with ulcers. We see the damages that human papilloma virus (HPV) does with cervical cancer in women (or in men with penile cancer). So they're definitely bugs. In my opinion, I never say “definitely”, but that's my hypothesis. I think everything is bugs that are out of balance.

This is the research we're doing. To me, when you look at COVID-19, What is COVID-19? COVID-19 is another virus (like Epstein Barr like Cytomegalovirus (CMV), like John Cunningham virus (JCV), like herpes) that basically mobilized and got into the gut. We were the lab that found COVID-19 in the stools—we published early on that we found COVID-19 in 8 patients and the virus was different. We saw the whole genome of the virus and the virus was different in everybody that we saw. When we saw that, (and we saw that COVID-19 inhabited the gut) my first process is, “Why did it inhabit the gut? Did it inhabit the gut because there was space there? And therefore, it just allowed itself to just penetrate?”

Remember, when you lose the good guys and you've got a dysbiosis—an imbalance—viruses will penetrate, and parasites will penetrate. We see it with COVID-19. And what we saw with COVID-19 is not only that it entered, but people started having herpes, shingles…people started having Epstein Barr Virus reactivated. They were tired and the fatigue lasted a longer time. Did COVID-19 work symbiotically together with Epstein Barr to trigger it to wake it up? And therefore, now you're dealing with not only 1 virus, but 2 viruses— or 3 or 4 that are inhabiting your gut. So when we started looking at COVID-19 in the stools, we said, “Well, let's look at what the bacteria is doing. What are our good guys doing? What are the bad guys doing?”

What we noticed is a group of bacteria that is in a phylum, and a phylum is basically the accumulation of microbes that are similar. When those microbes were in the phylum actinobacteria, there was very little of those microbes in that phylum in which people that had severe COVID-19 [were in]. In other words, you have severe COVID-19 (you have COVID-19 inhabiting the gut) but at the same time, your good bacteria, you're bifidobacteria (which is the billion-dollar industry of probiotics, right? We take all these probiotics because we believe that we're improving our guts, right?) are what we believe that these are the good guys.

When you see on a paper that patients that had severe COVID-19 had zero bifidobacteria in their gut, you have to ask the question—because that's what science is about. Science is about asking questions. You have to ask the question “Did COVID-19 kill the bifidobacteria? Or did COVID-19 Enter the gut?” Because the bifidobacteria was low. So when you look at people that were asymptomatic, you notice their bifidobacterium were super high, and they evacuated the virus. We once again ask the question, “Did bifidobacteria protect these people at the baseline in their colon from having severe COVID-19?” What we saw with the severe COVID-19 is that bifidobacteria levels were zero. What we saw with severe patients (and what we saw with the non-severe patients, or the asymptomatic) is that their bifidobacteria was higher.

Now when we looked at families—and that was the key to the paper that we published, like the most read paper at BMG gastro— when you see in the paper is that there are 20 patients that were high-risk and exposed to COVID-19. So the mother has a daughter who had 0 bifidobacteria, surprising for a 23-year-old to have 0 bifidobacteria. The mom was a pediatrician and had a lot of bifidobacteria. She took care of her daughter— fed her, changed her sheets, and she was exposed constantly to the virus for the 20 days, and she had it. In fact, we've picked up the virus and it go for 45 days later in her stools. She took care of her kid, you know, washed the sheets, washed everything, but never got COVID-19. Why? Well her bifidobacteria was super high. You know, vice versa.

Take for example, another mother with her son. He had 0 bifidobacterium—he was on a lot of medications… a lot of antibiotics over the years. He got COVID-19. The mom, who had good bifidobacteria levels, never got COVID-19 even when she was exposed to him, even when she washed him, fed him, etc. So that was the beginning of the pandemic. That was my question: “Why are these people not catching COVID-19? And why are these people catching COVID-19?”

Bifidobacterium was one of the clues. Obviously there are other clues, there are other microbes that play a role in protecting (or going against) us. We notice when bacteroides are high, and your bifidobacteria is low, that's called dysbiosis. That's an imbalance. You are supposed to have equal amounts. So bacteroides we noticed were high. Nitze, which is a species that is another phylum of our guts, was also low in severe patients but high in asymptomatic but exposed patients, and those who never got COVID. There is something in the microbiome that basically shows that something is happening with these microbes and the relationship of these microbes with each other, which protects us. Remember, bacteria are 20 times bigger than a virus. So, when a bacterium is 20 times bigger, you count on that bacteria to protect you.

Bifidobacteria is such an important microbe. That's why it is a trillion-dollar industry of probiotics, because it is the microbe that actually they just discovered is decomposing plastic. Imagine you have those microplastics in your gut from drinking from these water bottles every day. The water bottle stayed in your car and now you've got some microplastic in your gut—now you count on your bifidobacteria to evacuate that to decompose it.

So, “Have we lost bifidobacteria all over the world? Is that what's happening is that what we're seeing, you know, on a global picture? Is that why COVID-19 has penetrated our guts and has penetrated humanity?” Potentially. So we have to pay attention.