Can inflammatory bowel disease be permanently treated with short-term interventions on the microbiome?

Abstract

Inflammatory bowel disease, which includes Crohn’s disease and ulcerative colitis, is a chronic, relapsing and remitting set of conditions characterized by an excessive inflammatory response leading to the destruction of the gastrointestinal tract. While the exact etiology of inflammatory bowel disease remains unclear, increasing evidence suggests that the human gastrointestinal microbiome plays a critical role in disease pathogenesis. Manipulation of the gut microbiome has therefore emerged as an attractive alternative for both prophylactic and therapeutic intervention against inflammation. Despite its growing popularity among patients, review of the current literature suggests that the adult microbiome is a highly stable structure resilient to short-term interventions. In fact, most evidence to date demonstrates that therapeutic agents targeting the microflora trigger rapid changes in the microbiome, which then reverts to its pre-treatment state once the therapy is completed. Based on these findings, our ability to treat inflammatory bowel disease through short-term manipulations of the human microbiome may only have a transient effect. Thus, this review is intended to highlight the use of various therapeutic options, including diet, pre- and probiotics, antibiotics and fecal microbiota transplant, to manipulate the microbiome, with specific attention to the alterations made to the microflora along with the duration of impact.

Keywords:

• antibiotics
• diet
• fecal microbiota transplantation
• gut microbiota
• gut microbiota modulation
• inflammatory bowel disease
• prebiotics
• probiotics
• resilience
• stability
• stable microbiome

Financial & competing interest disclosure

This work has been supported by SUCCESS grant. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• While the exact etiology of inflammatory bowel disease (IBD) remains unclear, increasing evidence suggests that the human gastrointestinal microbiome plays a critical role in disease pathogenesis.

• Manipulation of the gut microbiome, via therapies such as diet, prebiotics, probiotics, antibiotics and fecal microbiota transplant has emerged as an attractive alternative for both prophylactic and therapeutic intervention against inflammation.

• Most evidence to date demonstrates that the adult microbiome is a stable and resilient structure, making it difficult for therapies targeting the microbiome to result in long-term, permanent changes.

• Short-term administration of therapies targeting the microflora often induces rapid changes in the microbiome, which then reverts to its pre-treatment state once the therapy is completed.

• Studies on dietary interventions demonstrate a strong association between long-term dietary habits and dominance of the gut microbiota by particular taxa. In contrast, short-term dietary interventions induce rapid changes in the microflora, but lack the capacity to modify the microbiome in a lasting manner.

• Probiotics, such as VSL # 3 and Escherichia coli Nissle 1917, has shown some promise in maintaining remission in ulcerative colitis (UC) patients. Despite the clinical benefit of these agents in UC, there is minimal evidence advocating for probiotic use in Crohn’s disease (CD), and there are limited data on the effect these agents have on the human microbiome in either UC or CD.

• While prebiotics, such as germinated-barley foodstuff, has demonstrated clinical benefit in UC patients, there is currently no substantial evidence arguing for or against prebiotics in the treatment of IBD, and few studies, if any indicate the long-term effect they have on the microflora.

• Short-term administration of antibiotics, which are typically utilized in complicated cases of CD, leads to rapid changes in the microflora, oftentimes within the first 24 h; however, cessation of therapy leads to return of microflora to baseline, and complications of antibiotics, such as Clostridium difficile infection, limit their long-term use.

• In the few studies assessing the impact of fecal microbiota transplant on the microflora of IBD patients, the microbiome tends to return to its initial (pre-treatment) state within 4 weeks of the completed therapy.

• Further long-term studies analyzing therapies targeting the microbiome over prolonged periods of time are necessary to ascertain whether this will allow for more permanent changes in the microbiome, and whether these microbial changes will translate into improved IBD outcomes.

Notes