Gut Microbiome Predicts Biologic Treatment Response in Inflammatory Bowel Disease

Conducting an analysis of a gut microbiome may help predict the likelihood of successful treatment with biologic drugs in patients with inflammatory bowel disease (IBD).
Biologics precisely target specific aspects of the immune response. Although these drugs have shown superior results to traditional therapies, some patients with IBD or other autoimmune diseases do not reap the same benefits as others.
Prior efforts have been made to determine which patients may respond to a biologic based on their symptoms and gene expression in the affected tissues; however, these efforts have only had modest success.
Based on considerable research that shows the gut microbiome plays a key role in several immune disorders, the investigators sought to determine whether it might also determine response to biologic treatment for IBD.
For the study, published in Cell Host and Microbe, investigators enrolled 85 patients with ulcerative colitis and Crohn’s disease who initiated treatment with vedolizumab (Entyvio).
Stool samples were taken prior to the start of treatment with vedolizumab, and at 14, 30, and 54 weeks. 
The investigators analyzed the stool samples for both the composition of the microbial population and for functional qualities, based on expression patterns of microbial genes.
Participants who achieved remission of IBD symptoms at 14 weeks were found to have a more diverse pretreatment microbial population that contained a greater abundance of potentially anti-inflammatory species compared with participants who did not achieve remission.
More importantly, the investigators were surprised by the differences in microbial functional patterns between patients who did and did not achieve remission, both before treatment and at 14 weeks.
Microbial changes observed in patients who were in remission at 14 weeks persisted for at least 1 year, indicating that early changes could identify the patients who are most likely to achieve and sustain a response to treatment.
“We are currently limited in our ability to predict which patients will respond to which therapies,” said lead author Ashwin Ananthakrishnan, MBBS. “Our finding that the pretreatment composition and function of intestinal bacteria could predict treatment response offers a novel additional tool for personalized therapy choice.”
For now, implementing microbiome sequencing into routine screenings is impractical because of the high costs. But the authors noted that as technology continues to improve and involve, it will likely reduce those costs.
“The ability to pick the treatment most likely to work for a patient would be enormously helpful both in helping achieve remission quickly and in avoiding exposures to drugs that would be unlikely to work, may be costly and may have adverse side effects,” Ananthakrishnan said. “In addition to testing this approach in larger groups of patients and with different drugs to see if it can reveal comparative effectiveness, we hope to use this data to develop targeted probiotics that may be able to adjust the population in those with an unfavorable baseline microbiome.” 

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