Bacteria as “Good Guy”: A Chat with Synlogic

Bacteria can be harmful; E. coli and salmonella have been known to cause food poisoning, and other bacteria are linked to serious diseases including cholera, bubonic plague and tuberculosis.
 
But many bacteria are both helpful and necessary, and may have a larger role in our overall health. An increased understanding of the gut microbiome – the bacteria and microorganisms in our gastrointestinal tract that perform critical functions like digestion and vitamin production – and the ability to easily reprogram bacteria to perform other functions, are changing the way researchers are tackling serious diseases.
 
AbbVie and Synlogic recently joined forces to take on this exciting scientific challenge, in a collaboration focused on developing new medicines for treating inflammatory bowel disease. The collaboration leverages Synlogic’s proprietary approach for a new class of synthetic biotic medicines that power the microbiome, and AbbVie’s expertise in metabolic and inflammatory diseases.

“We are looking at new ways to personalize therapy for complex diseases, including how drugs are delivered to target the right tissue, in the right patient, at the right time,” says Bradford McRae, Ph.D., discovery project director at AbbVie. “Technologies like Synlogic’s engineered bacteria are exciting because they may enable us to target only inflamed tissue in the gut, addressing disease at its root.”
 
We talked with Synlogic’s Dean Falb, Ph.D., chief technology officer, and Paul Miller, Ph.D., chief scientific officer, to get additional insight into the potential that reprogramming bacteria from the gut microbiome may hold in the treatment of serious, chronic diseases.

Dr. Paul Miller:  Research on the microbiome over the past decade has uncovered an astounding number of associations between health and the composition of our gut microflora. It’s now clear many digestive processes are determined by microbial action. Also, we know that animals raised in an environment where their gastrointestinal tracts are not colonized by any bacteria are extremely unhealthy and have poorly developed immune systems. And relevant studies show an association between gut microbiome composition and diseases like neurological condition and metabolic disorders, including diabetes and obesity.
 
Dr. Dean Falb: From a technology perspective, with the advances in genomic technologies, researchers have been able to sequence bacteria from the guts of healthy individuals, and found hundreds of different strains. More interesting, they are looking at the sequences in patients with certain diseases and finding differences in the strains of bacteria – they may be entirely unique, have a portion or all of a genetic sequence missing, and so on. This is helpful because we not only know of the broad disease associations, but also we can see how differences in bacterial strains impact individual diseases, giving us direction for how to think about developing new treatments.  

What does this tell us when we think about disease treatment?

Dr. Miller: Bacteria carry out all sorts of metabolic reactions that are important for our survival. In parallel, we know that there are patients with genetic defects that prevent them from being able to carry out certain types of reactions, such as those that may be performed in the liver. Because bacteria are so good at carrying out so many different reactions, it may be that we can co-opt this capability to perform a function missing in patients with these genetic defects. For example, a person may be missing a genetic factor in the liver that’s important for some process, but a gut bacterium has a similar capability. We could tackle the patient’s disease, not from restoration of the liver function, but by asking a gut bacterium to carry out that function.
 
Dr. Falb: That all is a possibility because while this research on the microbiome was being generated, there were fantastic advances in the field of synthetic biology – the ability to reengineer living cells to carry out new and different processes, or to sense things in the environment that lead to being able to react appropriately. Bacteria can easily be rewired to enhance their ability to carry out a particular function under certain conditions. 

What’s the potential for this type of approach?

Dr. Miller: We are still at the early stages of understanding how the many species of bacteria interact and work in communities. Right now, the engineered bacteria being created for therapeutic use are meant to move transiently through the digestive tract.  
 
But further down the road, as our knowledge grows, we envision permanently colonizing bacteria that are part of the normal gut flora of patients who have very serious chronic diseases. The bacteria could pick up a signal of a flare-up, for example, and respond very rapidly by delivering a certain medicine straight to the affected area. While it’s still a ways into the future, the momentum and direction of the science suggest it might be possible.
 
Dr. Falb: There’s also the potential to produce multiple therapies in one organism. For example, if engineered bacteria could recognize cancer cells and attack them, we could deliver multiple medicines from one engineered bacteria. Additionally, we would be able to restrict the area or region of the tumor where these bacteria would deliver the medicines, providing a more targeted approach to treatment.

Is the idea of utilizing bacteria in disease treatment a new one?

Dr. Falb: Not at all. In fact, more than 100 years ago, it was relatively common practice to try to treat a cancer patient’s solid tumors with certain types of bacteria. They found that bacteria in certain skin infections seemed to be effective against tumors, so clinicians tried isolating the bacteria in those skin infections and giving them to patients.
 
Physicians also used to take bacteria from patients and inject them into horses to create an immune serum. They would isolate the immune serum from the horse and give it back to the patient in an attempt to cure infections caused by those bacteria. This was long before small molecule drugs or antibiotics were discovered.
 
Dr. Miller: The point is that medicine isn’t one straight path. It twists and turns and sometimes things that were discovered a long time ago that went dormant may be rediscovered. It’s exciting to know that new technologies applied to these old ideas can help us come up with radically new ways to help patients.