A new review now published in the journal Digestive and Liver Disease suggests that new treatments for inflammatory bowel disease might come from combining antifungals with probiotics to promote a healthy balance of microorganisms throughout the gut.
The review's authors describe how they earlier discovered that certain bacteria and fungi appear to work together to form stubborn biofilms that can aggravate gut inflammation in Crohn's disease, a form of inflammatory bowel disease (IBD).
IBD is a long-term illness in which the immune system wrongly attacks the cells of the gastrointestinal tract, or gut, to cause painful inflammation. As well as pain, symptoms can include diarrhea and passing blood.
There are two main forms of IBD: ulcerative colitis, which affects the colon, or large intestine, and the rectum; and Crohn's disease, which can affect any part of the gut.
There are thought to be around 1.6 million people in the United States living with IBD, most of whom discovered that they had it before they reached the age of 35.
Friendly fungi essential to gut health
For some years, researchers have been using genetic tools to investigate how the trillions of microorganisms that live in the gut contribute to health and disease.
"Unfortunately," says lead author Mahmoud A. Ghannoum, Ph.D. - of University Hospitals Cleveland Medical Center in Ohio and Case Western Reserve University School of Medicine, which is also in Cleveland, OH - "most research has focused on studying only the bacteria while overlooking a key player, fungus."
In earlier work, Dr. Ghannoum and team used "deep sequencing" to study the genetic makeup of microorganisms in the mouth. This yielded "unexpected findings revealing that humans are colonized with numerous fungal species."
Then, in a later study, the researchers discovered that the guts of patients with Crohn's disease had much higher levels of two bacteria (Escherichia coli and Serratia marcescens) and one fungus (Candida tropicalis) than healthy relatives without the disease.
Further investigation in the laboratory showed that the three organisms "cooperate in such a way as to form large, robust biofilms capable of activating the host immune response."
While that study was not the first to reveal that collaboration between fungi and bacteria affects human health, it was the first to show a link to inflammation in Crohn's disease.
Probiotics should also tackle gut fungi
In the new review, the team revisits these findings and makes the case for combining antifungals with probiotics when considering new treatments for IBD.
They discuss how fungi and bacteria work together not only at the level of organisms, but also between "kingdoms."
The authors also point out that their earlier research not only revealed that fungi play a key role in gut health, but that it also shows how "overgrowth of the fungus due to imbalance" can damage the "mucosa," or lining of the gut.
They conclude that efforts to develop new probiotics should take into account the evidence on how fungi and bacteria may work together in IBD.
One approach, they suggest, might be to eliminate the overgrowth of undesirable fungi first, and then administer a probiotic that combines both beneficial bacteria and beneficial fungi to restore the balance in the gut.
"Our groundbreaking discovery that bacteria and fungi both play a critical role in health and disease has tremendous implications not only for understanding the disease process, but also for [the] development of potentially life-changing treatments for those who suffer from chronic digestive diseases."
Dr. Mahmoud A. Ghannoum