Nearly one million people in the United States suffer from ulcerative colitis (UC) and experience a host of symptoms that can significantly diminish quality of life. In severe cases, it can even be life-threatening. With no known cure and an unclear etiology, UC can present major treatment challenges and many patients struggle to find durable relief from symptoms.
Current ulcerative colitis treatment options include traditional small molecule drug therapies, biologics and biosimilars, nutritional supplements, and lifestyle modifications, but the relative effectiveness of each option varies depending on the patient. Additionally, most conventional drug therapies for ulcerative colitis are designed to treat only the symptoms of UC—and many come along with debilitating side effects—while leaving its root mechanisms unaddressed. However, in recent years, there has been increasing research interest in potential treatment strategies that directly target some of the underlying causes of UC symptoms in order to more fully alleviate gastrointestinal distress. As a result of these investigations, a team of Australian researchers introduced multidonor fecal microbiota transplantation (FMT) as a novel new treatment method in early 2017. The research team’s paper provides insight into the effectiveness of this intriguing option as well as shedding new light on why certain nutritional supplements may be more effective than some conventional UC treatment options.
Exploring the Potential of Fecal Microbiota Transplantation for UC
In March 2017, a group of researchers from the University of South Wales in Australia published a groundbreaking study in The Lancet on multidonor FMT, in which fecal samples from multiple healthy patients were transplanted into the colon of patients with active ulcerative colitis. The impetus for the study was the growing recognition of the role of microbiome composition in the pathogenesis of ulcerative colitis. The researchers hypothesized that transplanting fecal microbiota from multiple donors might alter the gut microbiota of patients with ulcerative colitis, which would ideally have measurable functional effects. In a randomized, placebo-controlled study of a sample population of 85 patients at three Australian hospitals, the researchers then successfully demonstrated that multidonor FMT could accomplish both aims: changing the composition of the gut microbiome and increasing the likelihood of remission in patients.
After the transplantations, the researchers used shotgun metagenomics to analyze the microbial composition of the patients’ gastrointestinal tracts. Not only did they find that there was a significant increase in the diversity of the gut microbiota in the treatment group when compared to the control group (who had received the placebo), but there were also noticeable shifts in the prevalence of certain bacterial taxa. Significantly, a number of these changes were clearly correlated with clinical outcomes.
One of the key findings of the study was that multidonor FMT resulted in a shift in the dominant bacteria in the gut microbiome from the genus Bacteroides to Prevotella. These are both genera of bacteria that are normally present in the gut, but their prevalence can vary. Although the implications of the shift after multidonor FMT are not fully clear, it opens up an exciting new avenue for exploration. The authors also observed that the presence of bacteria from the phylum Firmicutes were loosely correlated with symptom remission. This included bacteria from the genus Lachnospiraceae, which is a genus that other studies have associated with the production of butyrate, a chemical that plays a wide range of essential roles in the body. There were also several bacterial genera that were correlated with a lack of remission. Although it was unclear why these specific genera were not associated with remission, the researchers did note that many were involved in heme biosynthesis.
It is well-understood that the metabolic activities of bacteria in the gut play a key role in the functioning of the gastrointestinal tract, having both positive and negative impacts. Notably, the researchers found that changes in global bacterial metabolic function after FMT were also correlated with remission or lack thereof. Specifically, the results indicated that an increase in bacterial heme biosynthesis after FMT was associated with a lack of remission, while increases in starch degradation activity and short-chain fatty acid production were correlated with remission for ulcerative colitis patients.
The Benefits of Nutritional Supplementation
Multidonor FMT is not among the ulcerative colitis treatment options that are broadly available for patients today. However, the results of the Australian study provide insight into some of the options that are available, including multiple nutritional supplementation options. Of particular interest is the key finding that remission is associated with microbiome changes increase short-chain fatty acid production. While the breakdown of fibers by bacteria is the main source of short-chain fatty acids in the gut, they can also be introduced in supplement form. In recent years, anecdotal evidence for the effectiveness of short-chain fatty acid supplements like butyrate has been growing, and they have become increasingly popular among patients. The results of this study provide rigorous evidence that the presence of butyrate in the gut is associated with remission, which helps build a stronger evidence-based case for the effectiveness of butyrate supplements.
Omega-3 fatty acid supplementation is another ulcerative colitis treatment option that patients may want to consider. In multiple research studies, omega-3 fatty acid supplements have been associated with some of the very same benefits that the Australian research team found in patients who achieved remission after multidonor FMT, including an increase in overall microbial diversity and a shift in the prevalence of bacterial genera involved in butyrate production, such as Lachnospiraceae. Additionally, omega-3 fatty acid supplementation has been associated with a decline in the prevalence of bacterial species within the genus Faecalibacterium, which are also suspected to be involved in the exacerbation of UC symptoms.
In addition to butyrate and omega-3 fatty acids, probiotics and prebiotic supplements may also improve the gut microbiome. Like multidonor FMT, a probiotic supplement can improve the bacterial composition of the microbiome in patients with UC. Meanwhile, prebiotic fiber supplement can support the gut microbiome by introducing fibers that feed the “good” bacteria in the gut, giving them fuel to create beneficial metabolites like butyrate.
When considering nutritional supplements as ulcerative colitis treatment options, it is essential to recognize the relevance of supplement bioavailability. Recent research indicates that there is a wide range of factors that can affect the bioavailability of supplements and therefore their efficacy. For those taking omega-3 supplements, for instance, improper dosage and timing of intake may limit bioavailability, while bioavailability may be increased when formulators alter lipid oxidation levels or add omega-3 fatty acids to supplements and functional foods in an emulsified form. For patients with UC, finding a highly bioavailable supplement is particularly important because gut inflammation can interfere with nutrient absorption.
Considering Current Ulcerative Colitis Treatment Options and Looking Ahead to the Future
Despite the fact that ulcerative colitis remains poorly understood, it is clear from the latest research breakthroughs that the future of treatment is promising. Not only does the Australian study on multidonor FMT present a novel way to support remission in UC patients, it also sheds light on some of the nutritional supplements that are most commonly used by patients, helping to build on the anecdotal evidence by solidifying the research foundation for supplementation as a viable UC treatment option. As researchers continue to investigate potential future therapies, particularly those aimed at manipulating the gut microbiome, patients and practitioners can take advantage of insights like these when considering the currently available ulcerative colitis treatment options. Already, cutting-edge supplement manufacturers are developing more bioavailable supplements in order to allow UC patients to explore their potential therapeutic benefits. As a result, patients now have more and better options for creating well-tolerated multidisciplinary treatment plans and experiencing more complete relief from symptoms.
Constantini L, Molinari R, Farinon B, Meredino N. 2017. Impact of omega-3 fatty acids on the gut microbiota. International Journal of Molecular Sciences. 18(2):2645. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5751248/
Garud S, Peppercorn, M. 2009. Ulcerative colitis: Current treatment strategies and future prospects. Therapeutic Advances in Gastroenterology. 2(2):99-108. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002512/
Ghasemifard S, Sinclair AJ, Kaur G, Lewandowski P, Turchini GM. 2015. What is the most effective way of increasing the bioavailability of dietary long chain omega-3 fatty acids — Daily vs weekly administration of fish oil? Nutrients. 7(7):5628-45. https://www.ncbi.nlm.nih.gov/pubmed/26184297
Noriega BS, Sanchez-Gonzalez MA, Salyakina D, Coffman J. 2016. Understanding the impact of omega-3 rich diet on the gut microbiota. Case Reports in Medicine. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4808672/
Ottestad I, Nordvi B, Vogt G, Holck M, Halvorsen B et al. 2016. Bioavailability of n-3 fatty acids from n-3-enriched foods and fish oil with different oxidative quality in healthy human subjects: A randomised single-meal cross-over study. Journal of Nutritional Science. 5:e43. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5465811/
Owczarek D, Rocacki T, Domagala-Rodacka R, Cibor D, Mach T. 2016. Diet and nutritional factors in inflammatory bowel diseases. World Journal of Gastroenterology. 22(3):895-905. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4716043/
Parmasothy S, Kamm MA, Kaakoush NO, Walsh AJ, van den Bogaerde J et al. 2017. Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: A randomised placebo-controlled trial. The Lancet. 389(10075):1218-28. https://www.ncbi.nlm.nih.gov/pubmed/28214091