Tackling the Complexity of the Gut Microbiome for Better Treatments

An imbalance in gut microbe species is linked with gastrointestinal disease. Philip talked with the CEO and co-founder of the Swiss startup PharmaBiome, Tomas de Wouters, about the complexity of rebalancing the gut microbiome in these conditions.

The microbiome is a hugely complex ecosystem of microbes living all around the body. Different parts of the body have their own distinct microbiome, including the skin, mouth and gut. In the gut alone, we have 300-500 species of bacteria, all of which can interact with the host and with each other. “You have an ecosystem just like a rainforest,” de Wouters remarked.

PharmaBiome is a company based in Zürich, Switzerland. It’s developing treatments for gastrointestinal diseases that involve a disruption in the gut microbiota ecosystem such as Clostridium difficile infections and ulcerative colitis, an inflammatory bowel disease that causes painful ulcers.

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PharmaBiome microbiome ulcerative colitis gut

The company’s strategy is to rebalance the patient’s gut microbiome by transplanting carefully selected bacterial species that it grows in the lab. The company chooses which species to add into the mix by analyzing their functions in the microbiome, only including the species that help keep the ecosystem healthy.

Our main idea at the beginning was that the common denominator is function,” said de Wouter. Through this approach, PharmaBiome views the smallest ‘unit’ that performs a specific function in the gut not as a single species of bacteria, but rather a mix of them.

PharmaBiome’s approach is a ‘halfway house’ between other companies developing microbiome probiotic treatments. Companies like Enterobiotix and MaaT Pharma are testing the potential of fecal transplants, which transplant the entire gut microbiome. Although these transplants have shown promise for treating persistent Clostridium difficile infections, they contain many unneeded species, and potentially even dangerous strains for the vulnerable patient.   

On the flip side, other companies such as Microbiotica are developing treatments that focus on giving patients single strains of bacteria. While this method is simpler and more controlled than a full transplant, there is no guarantee that a single strain would thrive in the patient’s gut. PharmaBiome’s strategy, therefore, aims to mimic a fecal transplant, but using only the essential species.

pharmabiome gut microbiome bacteria species

Bacterial species in the gut. (Clockwise from top left): Streptococcus; microbial biofilm of mixed species, from the human body; Bacillus; Malassezia lopophilis.

Founded in 2015, PharmaBiome is based in the Swiss Federal Institute of Technology (ETH), where it developed the technology that it needed to culture the precise mixes of bacteria. “We got a year to work out our idea here at ETH, and we managed to have a proof-of-concept from scratch in one year,” explained de Wouters.

Now that PharmaBiome has tested its lead treatment in the lab and animal models, it’s now preparing to enter into the clinic. “The final confirmation is the clinical confirmation,” de Wouters said. “We have a compound on ulcerative colitis that we have been validating extensively and where we have a mode of action.

Before it can get to the clinic, however, the company plans to begin fundraising to fuel the development, as well as being open to partnerships. One big technical challenge is mass-producing these treatments at a consistent quality. “I don’t even need to tell the biotech community that the idea is the easy bit,” joked de Wouters. “The execution is the hard part.

Once the pipeline is established, de Wouters says that PharmaBiome plans to experiment further with this platform by combining different bacterial units to treat other diseases aside from ulcerative colitis.

As the company was incubated in ETH, de Wouters and his co-founder, Christophe Lacroix, initially thought that they could establish the company alongside their academic work. As the institution’s technology transfer department warned them though, they were wrong.

PharmaBiome microbiome ulcerative colitis gut bacteria

We went to tech transfer to say ‘we have this idea, we want to found the company, and do this during our postdoc,’” reflected de Wouters. “They brought us back to Earth and I’m quite grateful for that. You can’t just found a company on a 20% basis. You either go for it or you leave.

The microbiome field is at an early stage, with no treatments approved so far, and still needs more clinical trials to establish whether changes in the gut microbiome are the cause or just an effect of gastrointestinal disease. For de Wouters, the early stage of this field is not a bad thing though. “No matter what the solution will be, people will need the technology to deliver it and that’s why we have been working on that since the beginning.

Although it is young, the field is moving fast. In particular, big pharma companies are taking notice of biotechs working in this area and are already carving out territory by forming partnerships. Microbiotica and Enterome have both formed big partnerships with Genentech and Takeda respectively. “I think in the next few years we will see which therapeutic approaches make sense and we are very happy to contribute to that,” concluded de Wouters.



Images from Shutterstock and NIH Flickr under Creative Commons

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