UC and Gut Bacteria: Could Missing Microbes Hold the Key?
New research suggests the cause—and possibly cure—for ulcerative colitis can be found in your gut microbiome.by Jeanine Barone Health Writer
Editor's Note: This story is part of a new series on HealthCentral called "Get Your Ph.D.!", which is geared toward people who've got the basics of their condition down and want to up their expertise. Who's ready to go pro?!
If you have UC, you’ve probably been told it’s an autoimmune disease where the body’s immune system, which normally defends against invading pathogens (such as disease-causing viruses), instead attacks the colon or rectum, resulting in chronic inflammation. Recently though, scientists have begun to wonder whether something else is going on. What if there is another piece to the UC puzzle? What if ulcerative colitis is a disease that doesn't just mess with your gut, but is caused by your gut—or specifically, the absence of certain bacteria in it?
If that sounds all kinds of crazy to you, it’s understandable. Like most people, you probably associate bacteria with disease and infection—so the less you have, the better. But actually, the human body harbors trillions of microbes that typically exist in a state of harmony, and many of them are beneficial to your health. In recent years, it’s become clear that among the myriad nooks and crannies in your body where bacteria hang out, those in your gut—known as the gut microbiome—play an outsized role in your health. And that includes, it turns out, the risk for chronic diseases such as ulcerative colitis (UC).
“Manipulation of the gut microbiome either directly or indirectly is likely to play an important role in the treatment of ulcerative colitis and offer safe, effective, and targeted future therapy,” says Aida Habtezion, M.D., co-principal investigator of a new gut microbiome study, and associate professor of gastroenterology and hepatology at Stanford University School of Medicine. Here’s what the latest research shows.
How the Gut Microbiome Works
If all systems are operating normally, your large intestine (colon) serves as a home to a diverse mix of bacteria that produce and modify molecules that have beneficial physiological functions. This "good" gut bacteria protects the intestine from harmful bacteria that could invade it. It does this by releasing a specialized, anti-inflammatory and immune-beneficial substance called butyrate, a fatty acid. This, in turn, protects the innermost lining of the intestine (your intestinal barrier), which is key to a healthy gut.
The intestinal barrier is made up of a tightly knit network of cells that maintain the gut’s integrity. A healthy gut relies on the interactions between the gut microbiome and this barrier. If something upsets the balance between the good and bad bacteria in the microbiome or if there’s a dysfunction in the intestinal barrier, harmful bacteria can invade the barrier itself, resulting in the intestine’s immune cells being activated and, ultimately, chronic intestinal inflammation, like you find in people with UC. “The interaction between the host, intestinal microbiota, and anti-inflammatory metabolites these bacteria produce, may be a key factor in ulcerative colitis,” says Paul-Peter Tak, M.D., Ph.D., a professor of medicine at Amsterdam University Medical Centre in the Netherlands.
Exploring the Gut Bacteria and UC Connection
There are more than 1,000 different bacterial species that live in the gut microbiome. However, “many studies have found a reduced microbial diversity in ulcerative colitis as compared to healthy individuals,” says Dr. Habtezion. Also, the microbiome of people with UC tend to contain fewer beneficial bacteria (such as Lactobacillus, Bacteroides, and Eubacterium) while also containing more species known to be disease-causers. Studies looking at the composition of the microbiome in people with UC are full of inconsistencies, though, and raise the age-old chicken-or-egg question: Does an imbalance in the gut microbiome result in UC-related inflammation or the other way around? More research is needed before experts can say for sure.
Some of that research has just arrived, in the form of a newly published study from Stanford University School of Medicine. In it, scientists at Dr. Habtezion’s lab were able to pinpoint specific bacteria types that are missing in the gut microbiome of people with UC, compared to healthy individuals. It’s a eureka moment for experts in the field, who can finally point to concrete evidence that people with UC have significantly lower amounts of Ruminococcaceae in their microbiome, as well as lower levels of two kinds of anti-inflammatory byproducts of the bacteria.
Could Supplements Help?
If the absence or imbalance of gut bacteria does play as big a role in the development of UC as scientists suggest, it’s logical to wonder whether supplementing with prebiotics (dietary substances that help restore bacteria in the gut by enriching certain beneficial types) or probiotics (healthy microbes that inhibit the growth of harmful bacteria) might alter the composition of the gut microbiome to reduce inflammation and decrease the likelihood of flares.
New studies suggest some effectiveness in supplementation, in terms of improvements in remission or a reduction in inflammation among people with UC. Several probiotics have been explored, including E. coli Nissle 1917 (Mutaflor), VSL#3 (a preparation made of several bacterial species), and a yeast called Saccharomyces boulardii. But it is a new area of research in terms of the treatment of UC, and you should proceed with caution before self-treating with pre- or probiotics, experts caution. “More clinical studies are needed to determine their efficacy, and which type (or combinations) are efficacious in which subset of patients,” says Dr. Habtezion. “Not every patient will respond in the same manner to these interventions.”
Another cutting-edge approach: Transplanting fecal bacteria. A relatively new field in treating UC, the idea is that introducing gut bacteria from healthy people could restore normal bacteria in the microbiome of those with UC. Preliminary studies have found that people with UC who received a transplant of bacteria from healthy people experienced a remission in their condition. “There are promising results from early studies involving fecal transplantation to treat ulcerative colitis,” confirms Dr. Habtezion. “Currently, there are several clinical studies ongoing to address and optimize this treatment for ulcerative colitis.”
The Future of Microbes and UC
Targeting the gut microbiome might be a way of attacking UC early in its development before chronic inflammation takes over—or a way to ease inflammation in severe cases and reduce symptoms. But much is still unknown in this rapidly growing research field, including the full range of bacteria that play a role in UC and the exact mechanisms by which they work.
Medications targeting the intestinal inflammation as well as the dysfunctions in the intestinal barrier are being developed as are prebiotics and probiotics to help manage the disease. Meanwhile, eating a varied diet containing an array of fruits, vegetables, and whole grains can be a source of beneficial prebiotics. In addition, you may want to include foods such as yogurt, kefir and tempeh, that contain probiotics. As always, talk with your gastroenterologist first, because fiber and other carbohydrates could irritate the intestine of some people. And if something seems to be making your UC worse, stop eating it. As they say, sometimes you’ve got to go with your gut.
Bile Acids: Cell Host and Microbe. (2020). “Dysbiosis-Induced Secondary Bile Acid Deficiency Promotes Intestinal Inflammation.” ncbi.nlm.nih.gov/pubmed/32101703
Probiotics: PLoS ONE. (2020). “Assessing the Efficacy and Safety of Fecal Microbiota Transplantation and Probiotic VSL#3 for Active Ulcerative Colitis: A Systematic Review and Meta-Analysis.” ncbi.nlm.nih.gov/pmc/articles/PMC7077802/
Probiotics: Gastroenterology Clinics of North America. (2017). “Probiotics in Inflammatory Bowel Disease.” ncbi.nlm.nih.gov/pubmed/29173520
Fecal Transplants: JAMA. (2016). “Manipulating the Microbiome With Fecal Transplantation to Treat Ulcerative Colitis.” ncbi.nlm.nih.gov/pubmed/30644970
Gut Microbiome, Cause or Effect: Pathogens. (2019). “Alteration of Gut Microbiota in Inflammatory Bowel Disease (IBD): Cause or Consequence? IBD Treatment Targeting the Gut Microbiome.” ncbi.nlm.nih.gov/pmc/articles/PMC6789542/