Over the last few years, the human body's microbial population has been the subject of numerous discussions and controversies. But few topics have sparked as much interest as the concept of fecal microbiota transplantation, or FMT. This rather easy procedure has become a lightning rod for debates ranging from its effectiveness to ethical issues regarding donations.
The ultimate goal of FMT is to change the microbial population of the gut of an individual. We now know the key to good microbial health is a diverse population consisting of hundreds of different species of bacteria. If that diversity drops, commonly known as dysbiosis, problem can arise.
One of the more studied consequences of dysbiosis particularly in Canada is Clostridium difficile infection. This species usually is harmless in a nice diverse microbial population. However, if it can grow in the colon to a sufficient density, troubles can arise. The most common symptom is chronic diarrhea but other complications may occur requiring hospitalization. It may also be fatal in those with weakened immune systems such as the elderly.
What makes C. difficile even more worrisome is its ability to resist antibiotic treatment. While options are available, few are completely effective. Patients may end up having recurring infections leading to a vicious and possibly never ending cycle of infection.
Enter fecal transplantation. The practice was tested against C. difficile infection some twenty years ago and the results were impressive. People recovered and many did not suffer again. While researchers looked for the reason behind this dramatic turn of fate for patients, the same answer kept coming to the forefront. Diversity was re-established and the pathogen was no longer able to compete.
At first glance, this explanation may seem to be reasonable but there is one question left unanswered. How exactly did the C. difficile numbers drop? Most people naturally assumed other bacterial species waged war against the enemy. Yet, this never could be proven.
Now thanks to a group of Chinese researchers, we may have the answer. Instead of bacterial diversity, the team has shown in a clinical trial the reason for FMT success may be viral not bacterial in nature. The results suggest a shift in thinking is required when it comes to microbial therapy in which we may need to focus more on the entity known as the virome.
Back in 2011, an examination of the viruses living inside our gastrointestinal systems revealed an incredible diversity of species. Most of them were parasites of bacteria, known as bacteriophages, suggesting they may play a role in health and disease. Several researchers started down a new path of investigation into the vast variety of viruses - known as the virome - in the hopes of finding answers.
In 2012, the first of many discoveries linking the virome and illness was revealed. Based on an analysis of C. difficile patients, the disease appeared to be associated with a lack of bacteriophage diversity. At the time, the researchers couldn't tell if viral variability played a role in the disease. There simply wasn't enough knowledge of the virome at the time. But since then, researchers have worked hard to understand the impact of viruses on our health.
This is where the Chinese team's work comes to light. The group performed FMT on nine of twenty recruited individuals. Fecal samples were taken from both donors and recipients before the procedures as controls. Then the feces of recipients were sampled at two, four, ten and sixteen weeks after treatment. The viral populations were examined and categorized to determine the level of diversity. With any luck, the team would be able to see differences in the viral composition in the recipients.
When the results came back, the team was pleased to see an increase in diversity of viruses in recipients. This eventually led to a decrease in C. difficile and resolution of infection. As to how this occurred, the team found a decades-old ecological theory known as "kill the winner" appeared to be occurring. The introduction of a wide array of viral species led to a fierce competition in which the viruses present became the minority and eventually lost out to the majority. As this happened, the C. difficile ended up losing ground and eventually disappeared, presumably falling victim to some of the viruses in the mix.
The results of this experiment provide a glimpse into how viruses may offer a new direction for C. difficile treatment. We also may be able to use viral diversity as a marker of a good donor. This could help ensure FMT is effective every time.
While this future benchmark for FMT is still years away from the average clinic, it may be useful in cases where FMT is desperately needed to resolve severe infections. By having the right diversity in place, these treatments may assist in resolving the condition before it is too late. Considering the impact of C. difficile on patients, this may be welcome news to doctors and other health professionals.
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