Using microbes to treat infections (microbial therapeutics): Dr. Brian Klein

What if doctors could use microbes to treat infections? It might seem counterintuitive at first because, well, aren’t the microbes the problem? 

Not really. Our bodies have microbes living in and on them, which is a good thing. These organisms, called the human microbiome, help keep us healthy. Because of the amazing benefits of having these microorganisms as a part of us, why couldn’t we try and take bacteria or other microbes that are considered “healthy” and use them to fix some of the problems we experience due to “bad” microbes? 

There are numerous companies developing ways to use microbes to fix microbial problems. So, in this podcast episode, I chat with Dr. Brian Klein. He is the co-founder and CEO of BrickBuilt Therapeutics, a company that is developing microbiome-based therapeutics to treat infections of the mouth.

We discuss the oral, skin, and gut microbiomes of humans and the potential to treat diseases or disorders affecting those sites of the body using microbes.

In this episode, you will learn about…

• The human microbiome
• BrickBuilt Therapeutics: an oral microbiome therapeutics company
• C. difficile infections and fecal transplants
• Microbiome-based therapeutics for C. difficile infections
• Process of turning a microbiome-based discovery into a product
• At-home microbiology activity: sequencing microbiomes

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What is the human microbiome?

When people hear mention of the human microbiome, they often think of the gut microbiome because it is the most well-studied area. But the human microbiome includes all different sites on the human body, including the skin, nasal, and oral cavity. 

The term microbiome tends to be used in different ways. Most people who are not microbiome experts will use it interchangeably with the word “microbiota,” or the microbes that live in and on us. (So, I usually do the same in my content to make it accessible.)

“It can get a little contentious when you hear certain terms and who you’re talking to, but [the microbiome] is the collection of the microbes (bacteria, virus, fungus, archaea), in one space, and all of the genes that they contain,” says Brian.

“Every niche or specific location can have a microbiome.” The skin microbiome can then be broken down into different sections of skin, like the armpit microbiome and belly button microbiome.

Some microbes are common between people, and some are not. Healthy people can have different microbiomes depending on their environment or what they eat.

It’s important to note that the term microbiome goes beyond the human body. Different parts of the Earth have microbiomes: water, air, and soil. Each Earth microbiome can be broken down into different sub-niches. For example, a water microbiome can be ocean, lake, and pond microbiomes.

To learn more about the microbiome, check out this previous Joyful Microbe post.

BrickBuilt Therapeutics: an oral microbiome therapeutics company

With the human microbiome in mind, we can move on to the idea of using these amazing microbes that live in and on us to treat diseases and disorders. Brian’s company BrickBuilt Therapeutics specializes in the oral microbiome. They are developing novel therapeutics for oral diseases because the diseases he works on have a basis in the microbiome. Here are a few examples Brian shares of the specific bacteria that cause diseases: cavities and Streptococcus mutans, periodontal disease (gum disease) and Porphyromonas gingivalis, and oral candidiasis (thrush) and Candida species (fungi).

The therapeutics his company is developing aims to replace the typical invasive interventions, like surgery and antibiotics. For example, cavities are drilled and filled, and gum disease requires deep cleaning and potentially gum surgery. These are both painful and expensive. Broad-spectrum antibiotics or antifungals are also commonly used, which can lead to antimicrobial resistance.

Brickbuilt Therapeutics is one of the numerous companies developing microbial therapeutics (or microbiome-based therapeutics) — using healthy microbes as treatments — also called “next-generation probiotics.” The idea is to isolate microbes from healthy people and use those microbes to help prevent or resolve a specific disease.

C. difficile infections and fecal transplants

Microbial therapeutics build on the concept behind fecal transplants. They cure the infection by remodeling the microbiome. Poop from a healthy human is put in someone to replenish their gut microbiome when they experience recurrent Clostridioides difficile (C. difficile or C. diff) that will not respond to antibiotics. And fecal transplants work remarkably well with 80% to 90% resolution.

But how do people get C. diff? In some people, it’s always present in their gut — 0-15% of young, healthy people (with no apparent diseases) in the general population carry it. Others acquire it through interactions with people outside of a hospital setting (community-acquired) or while in the hospital (hospital-acquired). Once a person has C. diff (which they may be completely unaware of) and takes a broad-spectrum antibiotic for some other infection, they are at risk for severe infection. The antibiotic indiscriminately kills the microbes in their gut, leaving an opening for antibiotic-resistant C. diff to take over.

Potential problems can accompany fecal transplants. The donors of the poop must be truly healthy. So, they go through a rigorous screening process to approve their samples, which are kept in repositories. If a person who appears as healthy carries in their stool a multi-drug resistant E. coli strain that hasn’t caused them a problem, their stool could be fatal to the person who receives the transplant.

Microbiome-based therapeutics for C. difficile infections

Microbial therapeutics companies are making significant progress in the gut microbiome space with C. diff infections. Companies like Vedanta Biosciences, Seres, Finch, and Rebiotix are leveraging the success of fecal transplants. They seek to determine the microbes necessary to cure C. diff to create a prescription probiotic.

The difference between microbial therapeutics for C. diff and fecal transplants is that they will be more precise, containing specific microbes at specified levels. So, it’s like the difference between fermented foods and probiotics. The particular species and levels of those species are not always known with fermented foods but are defined in probiotic products.

With more precision, companies are developing microbial therapeutics for C. diff infections that eliminate the risks of potential pathogens in fecal transplants. Similar to how Brickbuilt Therapeutics isolates oral microbes that may help oral diseases, these companies isolate bacteria from healthy people’s stool and determine which bacteria will cure the disease. These isolated bacteria are then grown individually and put into a pill in a “curative” combination of microbes.

A simplified example Brian gave is if a hypothetical healthy person’s gut has 100 species of bacteria, but only 5 are necessary to cure their disease, then the companies grow those 5 species and combine them in a pill.

These next-generation probiotics go through the rigors of clinical trials and FDA approval. So, they will be considered drugs.

Part of the process of confirming how well these microbiome-based therapeutics work is determining whether the bacteria in the pill colonize the gastrointestinal tract for at least long enough to cure the infection and prevent the recurrence of C. diff. The companies must demonstrate a causal relationship between the species in the drug colonizing and curing and preventing the disease.

Other companies are seeking to create microbiome-based therapeutics targeting the health of other areas of the body, such as skin (DermBiont) and vaginal (Luca Biologics). “I’m glad that both investors and academics and governments realize that funding for all the microbiome-based diseases is important,” says Brian.

How will people access microbiome-based treatments?

The microbiome-based treatments described above will be prescribed by a doctor or dentist. They will go through clinical trials and the FDA approval process and be regulated as a drug. These are called LBPs, or live biotherapeutic products, says Brian. However, spin-offs or over-the-counter versions may become available at local drugstores, health food stores, or online.

Some companies are going the cosmeceutical route, like AOBiome (skin spray) and BrightCure (UTI treatment), making their products available to anyone.

So, it all depends on the regulatory space the drug or substance is in, Brian says. Specific rules dictate how foods, ointments, and medications are treated and how rigorous of a process they must go through before being sold.

We may see these types of products coming to market very soon. Some of the cosmeceutical products are already available. For the C. diff treatments, Brian is hopeful we will see some of them within the next couple of years.

These microbiome-based treatments can either replace existing drugs or provide a solution to a problem that had none. So, the prospects are exciting indeed.

What is the process of turning a microbiome-based discovery into a product people can use?

The process of taking a “cool scientific discovery” and making a product has numerous steps. Here, Brian shares a hypothetical scenario. In this example, an academic research lab conducts a large-scale study looking for a cure for Staph infections (skin disease caused by Staphylococcus aureus). They search for a microbial therapeutic (bacteria) from samples from a cranberry bog to inhibit Staph.

1. Academic researcher finds bacteria from a cranberry bog that can stop Staph growth or infection progression.
2. Get a patent.
3. Write a paper on it.
4. Start talking to companies or venture capital firms, either:
   • large traditional antibiotics companies like AstraZeneca
   • smaller, newer, novel, microbial therapeutics companies like DermBiont. 
5. Determine how to administer the treatment. It could be a lotion containing a live microbe or dead lysed (exploded) bacteria, using the metabolites this bacterium produced.
6. Decide on the regulatory route:
   • FDA + clinical trials: test safety, efficacy, and effectiveness.
   • Dietary supplements and nutritional supplements for healthy adults (least regulated and easiest to get approval): Get approval for the bacterial strain as “generally recognized as safe” (GRAS), meaning it can be consumed for many, many years. The regulatory body may also want to see the genome sequence of the bacteria to ensure it is not resistant to antibiotics. The company may also put the product through a phase one healthy volunteer trial to demonstrate it is truly safe. The language you can use to describe the product is limited: you cannot say it is curative of disease.
7. Scale enough to produce it for people around the world.

At-home microbiology activity

Sequence your microbiome! Numerous online companies have sampling kits you can purchase to see what microbes live in your gut (or any niche you are interested in). Swab your skin, nose or submit a sample of your stool and send it to the company. They will sequence the microbes (usually bacteria) present in the sample. 

You could run an experiment where you test if a product changes your microbiome. For example, if you have dry skin, you could sample your skin before and after using a moisturizing product. Brian tracked the progression of his child’s gut microbiome from birth to six months. He also sampled his dog’s stool and skin to see how those microbiomes changed over time.

Keep in mind that companies usually focus on a specific type of sample. The type of sample affects how they perform their analyses. So, you wouldn’t want to submit a sample from your gut to a skin microbiome company because they expect to see skin microbes, not gut microbes. So, make sure you select the one that will suit your purposes. And have fun!

As a disclaimer, I am not implying that sequencing your microbiome will somehow provide immense benefits, healthwise or otherwise. This activity is meant for fun and learning, not for the diagnosis of a condition. Also, I’m not listing out all of the companies that do these types of tests because this article is not intended to be an advertisement for any of them. However, through a Google search, you can find many different companies that sell kits for a particular area of the body and/or sample type.

Links & Resources

This post contains affiliate links — see my disclosure policy.

• microBEnet: the microbiology of the Built Environment network (website)
• More info on fecal transplants and C. diff infections (Joyful Microbe blog post)
• Whole-Body Microbiome – B. Brett Finlay PhD, Jessica M. Finlay PhD (book)
• How The Bacteria In Our Mouths Cause Tooth Decay (And How to Prevent It) (Joyful Microbe blog post and podcast episode)

Connect with Dr. Brian Klein

Brian is the co-founder and CEO of BrickBuilt Therapeutics, an oral health company developing treatments and preventions for oral diseases via the microbiome. Brian holds a PhD in molecular microbiology from Tufts University, completed a postdoctoral fellowship at the Forsyth Institute, and prior to BrickBuilt, worked in the microbiome industry space at Vedanta Biosciences and Dermbiont for 4 years. He’s also an avid athlete, competing in rowing, running, triathlon and canicross….and has actually been able to weave his athletic passions with his scientific passions throughout his career.

Connect with Dr. Brian Klein: BrickBuilt Therapeutics, LinkedIn, Twitter (personal), Twitter (BrickBuilt)