Ventura Clinical Trials

Founded by Leading experts in Gastroenterology and Cardiology. It is a physician owned company with over 23 years of experience in clinical trials.

The Microbiome and Inflammatory Bowel Disease

The Microbiome and Inflammatory Bowel Disease
The Microbiome and Inflammatory Bowel Disease

Sabine Hazan Steinberg

Daniel Frochtzwajg

Jessica Murray

Sabine Hazan Steinberg MD, Gastroenterology/Hepatology/Internal Medicine Physician, CEO, Ventura Clinical Trials, CEO, Malibu Specialty Center Dr. Daniel Frochtzwajg DO, Research Assistant, Ventura Clinical Trials Jessica Murray BS, Research Assistant, Ventura Clinical Trials, Ventura, CA

Ulcerative colitis (UC) and Crohn’s disease are the two chronic and progressive inflammatory states that commonly define inflammatory bowel disease (IBD). UC is typically characterized by continuous mucosal inflammation that involves that rectum and colon and often presents as bloody diarrhea. In Crohn’s disease, inflammation is spotty, transmural and can be observed in any portion of the gastrointestinal tract. IBD affects roughly 1.4 million people in the United States and some 2.2 million in Europe.5,6 The steadily increasing incidence and prevalence of IBD, as well as the association of IBD and urban living, suggests that environment plays a critical role in the development of these diseases.8,13 This hypothesis, in conjunction with the documented variations in gut microbiome associated with industrialization and geography,3 has led researchers to pursue the intestinal microbiota as an avenue for diagnostic and therapeutic intervention.

It is thought that a shift in composition of the intestinal microbiome may contribute to the development of IBD in genetically susceptible individuals. Initially hinted at by studies demonstrating such things as a reduced risk of IBD in breastfed infants or increased risk in those with low vitamin D levels,1,2,10 the new age of bioinformatics has enabled corroboration of this theory. One example of the complex genetic-microbe interplay is a study by Ijaz et al.. demonstrating that adult relatives of patients with Crohn’s disease had less diverse intestinal microbiota than healthy adults unrelated to IBD patients.4

While there is no singular microbe responsible for IBD, gut dysbiosis is clearly implicated.5 An overall reduction in microbial diversity has been observed as well as specific, relative increases and decreases in “good” and “bad” microbes.5,9,12 In Sartor and Wu’s extensive 2017 review, Roles for Intestinal Bacteria, Viruses, and Fungi in Pathogenesis of Inflammatory Bowel Disease and Therapeutic Approaches, the authors distill the latest documented genetic compositional changes in the intestinal microbiome of IBD patients.12 They identify the overarching theme of the associated dysbiosis as a decrease in known “protective” bacteria such as Bifidobacterium species and an expansion of potentially inflammatory microbes like Proteobacteria, Fusobacterium species, and invasive E. coli.12

The common treatments for UC and Crohn’s, including immunosuppressive therapies, mesalamine, glucocorticoids, and tumor necrosis factor antagonists, rarely induce remission and colectomy is too often an undesirable endpoint. Furthermore, an IBD patient’s quality of life can be significantly diminished when treated with conventional therapies.17 However, like the trend of fecal microbiota transplantation (FMT) for the treatment of Clostridium difficile infection, there is promising evidence that a similar approach will prove efficacious in treating UC and Crohn’s, especially given the increasingly predictable intestinal microbiome perturbation. In one of the premier studies of alternative treatments for IBD, Moayyedi et al. demonstrate, in a randomized controlled trial, that FMT can induce remission in UC patients.7 Researchers used the Mayo score for UC, which includes scores for stool pattern, rectal bleeding, endoscopic findings, and physician assessment (scores ranges from 0-12, with higher scores correlating with increased disease severity) to assess patients. Eligible enrollees were adults 18 years or older with active UC determined by a Mayo score ≥4 (with an endoscopic score ≥1); remission was defined as a Mayo score <3 at seven weeks. FMT from healthy donors was completed via retention enemas administered once weekly for six weeks. Overall, 9 of the 38 patients in the FMT treatment arm achieved remission, compared to 2 of the 37 patients in the placebo arm. Moreover, there was no difference in serious adverse events between the two groups. In another promising prospective, uncontrolled study, by Uygun et al. response of UC patients to FMT was examined.14 Responders were defined as a decrease in Mayo score ≥30%. 21 patients in the study, 70% of the subjects, were ultimately classified as responders. While 9 patients were categorized as non-responders, there was still improvement in CRP and hemoglobin levels after FMT.

Despite the positive findings mentioned above, there is conflicting data, and in another RCT, Rossen et al.11 did not demonstrate a difference in the remission rate of FMT vs. placebo. However, increased intestinal microbiome richness following FMT has been shown in patients with Crohn’s, and there is evidence to suggest that FMT donor species richness determines efficacy of FMT treatment for IBD.15,16

Ultimately, while current data is cause for optimism, more foundational research is necessary to characterize the microbe-gene interaction and define a treatment paradigm.

 

 

References

1. Ananthakrishnan, A.N., et al. “Higher predicted vitamin D status is associated with reduced risk of Crohn’s disease.” Gastroenterology, vol 142, no. 3, 2012, pp. 482-89., doi: 10.1053/j.gastro.2011.11.040.
2. Barclay, A.R., et al. “Systematic review: the role of breastfeeding in the development of pediatric inflammatory bowel disease.” Journal of Pediatrics, vol 155, no. 3, 2009, pp. 421-6., doi: 10.1016/j.jpeds.2009.03.017.
3. Gupta, Vinod K., et al. “Geography, Ethnicity or Subsistence-Specific Variations in Human Microbiome Composition and Diversity.” Frontiers in Microbiology, vol 8, no. 1162, 2017., doi: 10.3389/fmicb.2017.01162.
4. Ijaz, Umer Zeeshan, et al. “The distinct features of microbial ‘dysbiosis’ of Crohn’s disease do not occur to the same extent in their unaffected, geneticallylinked kindred.” PLoS ONE, vol 12, no. 2, 2017., doi: 10.137/journal.pone.0172605.
5. Lane, Erin R., et al. “The microbiota in inflammatory bowel disease: current and therapeutic insights.” Journal of Inflammation Research, vol 10, 2017, pp. 63-73., doi:10.2147/JIR.S116088.
6. Loftus, E.V. Jr. “Clinical epidemiology of inflammatory bowel disease: incidence, prevalence, and environmental influences. Gastroenterology, vol 126, no. 6, 2004, pp. 1504-1517., doi: 10.1053/j.gastro.2004.01.063.
7. Moayyedi, Paul, et al. “Fecal Microbiota Transplantation Induces Remission in Patients with Active Ulcerative Colitis in a Randomized Controlled Trial.” Gastroenterology, vol 149, no. 1, 2015, pp. 102-109., doi: 10.1053/j.gastro.2015.04.001.
8. Molodecky, N.A., et al. “Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review.” Gastroenterology, vol 142, no. 1, 2012, pp. 46-54., doi: 10.1053/j.gastro.2011.10.001.
9. Morgan, X.C., et al. “Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment.” Genome Biology, vol 13, no. 9, R79, 2012., doi: 10.1186/gb-2012-13-9-r79.
10. Penders, J., et al. “Factors influencing the composition of the intestinal microbiota in early infancy.” Pediatrics, vol 118, no. 2, 2006, pp. 511-521., doi: 10.1542/peds.2005-2824.
11. Rossen, N.G., et al. “Findings from a randomized controlled trial of fecal transplantation for patients with ulcerative colitis.” Gastroenterology, vol. 149, 2015, pp. 110-118., doi: 10.1053/j.gastro.2015.03.045.
12. Sartor, R. Balfour, and Gary D. Wu. “Roles for Intestinal Bacteria, Viruses, and Fungi in Pathogenesis of Inflammatory Bowel Diseases and Therapeutic Approaches.” Gastroenterology, vol 152, no. 2, pp. 327-339., doi: 10.1053/j.gastro.2016.10.012.
13. Soon, Ing Shian, et al. “The relationship between urban environment and the inflammatory bowel diseases: a systematic review and meta-analysis.” BMC Gastroenterology, vol 12, no. 51, 2012., doi: 10.1186/1471-230X-12-51.
14. Uygen, Ahmet, et al. “Fecal microbiota transplantation is a rescue treatment modality for refractory ulcerative colitis.” Medicine, vol 96, no. 16, 2017., doi: 10.1097/MD.0000000000006479.
15. Vaughn, Byron P., et al. “Increased Intestinal Microbial Diversity following Fecal Microbiota Transplant for Active Crohn’s Disease.” Inflammatory Bowel Disease, vol 22, no. 9, 2016, pp. 2182-90., doi: 10.1097/MIB.0000000000000893.
16. Vermeire, Severine, et al. “Donor Species Richness Determines Faecal Microbiota Transplantation Success in Inflammatory Bowel Disease.” Journal of Crohn’s and Colitis, vol 10, no. 4, 2016, pp. 387-394., doi: 10.1093/ecco-jcc/jjv203.
17. Wei, Yao, et al. “Fecal Microbiota Transplantation Improves the Quality of Life in Patients with Inflammatory Bowel Disease.” Gastroenterology Research and Practice, vol 2015, 2015., doi: 10.1155/2015/517597.

Leave a Reply

Your email address will not be published. Required fields are marked *

This site uses Akismet to reduce spam. Learn how your comment data is processed.