A new study proposes that by eliminating the “bad” bacteria in the gut flora and introducing “good” bacteria, effective treatment of Crohn’s disease may be possible
Researchers from the Perelman School of Medicine at the University of Pennsylvania have made an astounding discovery. They have identified a bacterial enzyme that may be responsible for tampering with the gut flora and, as a result, triggering Crohn’s disease – a painful, inflammatory bowel disease that affects over millions of individuals on a global level.
The new study, published in the journal Science Translational Medicine, proposes that by eliminating the “bad” bacteria in the gut flora and introducing “good” bacteria, effective treatment of Crohn’s disease may be possible. “Because it’s a single enzyme that is involved in this process, it might be a targetable solution. The idea would be that we could ‘engineer’ the composition of the microbiota in some way that lacks this particular one” said Dr. Gary D. Wu, lead author of the study and associate chief for research in the division of Gastroenterology at the Perelman School of Medicine at the University of Pennsylvania.
More “bad” than “good” bacteria
A disruption in the balance in the gut flora is known as dysbiosis. It is generally triggered by environmental stressors, such as antibiotics or intestinal inflammation. It is also believed to be responsible for triggering Crohn’s disease and other inflammatory diseases, although the mechanisms are not quite well understood.
Perelman researchers found that Proteobacteria, a type of bacteria considered to be “bad” bacteria, preys on the urea, which is a waste product that can end up in the colon. In turn, the urease enzyme transforms the urea into ammonia, which is then reabsorbed by the bacteria to form amino acids. These specific amino acids are associated with the development of dysbiosis in Crohn’s disease. Controversy, “good” bacteria may be a promising approach to reinstating a healthier gut flora and treating the disease. “The study is important is because it shows that the movement of nitrogen into bacteria is an important process in the development of dysbiosis. It also proves using a single enzyme can reconfigure the entire composition of the gut microbiota” said Dr. Wu.
In their human study, Dr. Wu and his fellow colleagues sought to identify the role of the “urea into ammonia” process in dysbiosis by analyzing stool samples gathered from 90 children with Crohn’s disease, and comparing them to 26 children in good health. They found that fecal amino acids were connected to dysbiosis in Crohn’s disease and they also found a rich amount of Proteobacteria in the patients.
The findings led the researcher team to turn to an animal study, which involved monitoring the “urea into ammonia” process in mice to determine whether the mechanisms may be targetable solutions for Crohn’s disease.
A delicate balance of different bacteria
In their previous research, Dr. Wu and his fellow colleagues aimed to wipe the mice’s gut floras clean, in order to make room for a newly established bacterial community. They started off by treating the mice with antibiotics (more specifically, neomycin and vancomycin), as well as with polyethylene glycol, which is a colon cleansing agent.
In their current study, the researchers introduced Escherichia coli, which is a single bacterial species, in order to determine its effect on the mice’s ‘clean’ gut floras. They found that if the E.coli was negative for urease, the mice experienced improvement in their intestinal health. However, if the E.coli was positive for urease, the mice experienced severe intestinal inflammation and colitis.
The patients involved in the human study were treated with the same antibiotics and polyethylene glycol, which helped to diminish the quantity of bacteria in their gastrointestinal tracts. “Now that we can effectively reduce bacterial load in humans it may now be possible to engineer the microbiota into a different configuration in a manner similar to what we have achieved in mice. Although we’re closer now, there is still more work to be done” stressed Dr. Wu.
A new study conducted by Perelman researchers in collaboration with the Children’s Hospital in Philadelphia is ongoing to further analyze this approach. The researchers are monitoring patients with refractory Crohn’s disease and using a method that focuses on altering the gut flora. “The outcomes of this study and the analysis of collected biospecimens will be an important first step in building a technology platform to engineer a beneficial composition of the gut microbiota for the treatment of inflammatory bowel diseases” explained Dr. Wu.
Improving disease outcomes and quality of life
Healthy gut bacteria play an important role in regulating digestion, as well as controlling the immune system. But what happens when the balance is thrown out of whack? Infection. Generally, antibiotics are used to treat infection, but they can also kill off good bacteria, thus making the gastrointestinal tract susceptible to “bad” bacteria.
This is where probiotics come in. Probiotics encourage the growth of “good” bacteria in the gastrointestinal tract. They can be found in several foods, including most yogurts. When consumed, they help to eliminate less beneficial strains of bacteria, thereby keeping the lining of the gastrointestinal tract healthy and strengthening the immune system.
Research shows that there are several ways to support healthy gut bacteria and to potentially prevent the onset of IBD. These include the following:
- Eating plenty of fruits and vegetables;
- Increasing intake of fermented foods or probiotics;
- Drinking sufficient amounts of water;
- Exercising on a regular basis;
- Lowering the use of non-steroidal anti-inflammatory drugs;
- Limiting alcohol intake;
- Quitting smoking;
Unfortunately, for those who are living with inflammatory bowel diseases like Crohn’s disease, traditional treatments often fail to provide complete relief. As a result, researchers and healthcare professionals are continuously searching for a greater understanding of the disease and the development of new treatment options.
For quite a while now, the gut flora of patients with Crohn’s disease has been the main topic of discussion. Treatments that aim to alleviate symptoms brought about by this disease can also disrupt the flora’s structure and behavior. For this reason, the relationship between the two remained unclear until recently.
Now, new research is shedding light on the association between treatment of Crohn’s disease and gut health, which will undoubtedly lead to the introduction of more effective treatment options.