The Microbiome in Crohn's Disease: Role in Pathogenesis and Role of Microbiome Replacement Therapies

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Key points

  • Patients with Crohn's disease have decreased microbial diversity, which plays an important role in the pathogenesis of Crohn's disease.

  • Microbial restoration therapies are being studied for management of Crohn's disease and may be an adjunct to standard therapies in the future.

  • It may be feasible to modify the gut microbiota community structure or function to treat patients with Crohn's disease with targeted therapies via individual agents, such as probiotics, bacterial consortia, or even dietary

Crohn's disease and altered microbiome

Bacterial dysbiosis is likely a causative factor and an outcome in patients with Crohn's disease.4 Although dysbiosis may develop as a result of bowel inflammation, dysbiosis may also have a role in perpetuating chronic inflammation. Studies of the gut microbiota in patients with Crohn's disease demonstrate an increase in pathogenic microorganisms, whereas populations of normal commensal phyla are diminished.5, 6 In one interesting study, pretreatment gut microbial samples from patients with

Evolution of Microbiome

Following birth, humans develop their gut microbiota through a variety of mechanisms. The mode of delivery (whether vaginal birth or birth by caesarean section), diet, and other environmental factors influence the microbial community as it evolves from a simple community containing a core set of resident bacteria to a more complex, diverse community. In early childhood the microbiota shifts in response to the environment including dietary influences, antibiotic exposure, and illness.

Microbial restoration therapies in Crohn's disease

Because a perturbed microbiome is associated with Crohn's disease, it is conceivable that microbial restoration therapies could be useful in management of Crohn's disease. In patients with Crohn's disease, an understanding of the differences in composition of protective versus inflammatory bacteria and their down-stream metabolic functions may be useful to discover microbial therapeutic targets. It is well known that there is a limited role of antibiotics (treatment of abscesses and fistulae)

Prebiotics, probiotics, and postbiotics in Crohn's disease

As greater insight into the influence of the gut microbiota on the host immune response is gained, there is a need to explore ways to manipulate the microbiota or its function to modulate the host immune response and restore health. There have been many attempts to shape the gut microbial community with prebiotics and probiotics in patients with Crohn's disease with minimal efficacy. This apparent lack of efficacy may be in part caused by difficulties in administering known and consistent

Microbial restoration therapies in Crohn's disease: more questions than answers

Microbial restoration therapies for Crohn's disease should be carried out only under research settings with an investigation drug use application from the Food and Drug Administration. Because microbial dysbiosis in Crohn's disease is likely a causative factor for and a result of underlying inflammation, microbial restoration therapies remain a major challenge in 2017. The exact nature of the perturbation of the microbiome is not completely understood and it has not been possible to

Microbial restoration therapies in Crohn's disease: a closer look at 2050

With ongoing research, it may be possible to manage patients with Crohn's disease with microbial restoration therapies in addition to conventional immunosuppression medications. Potential steps to tailor therapy for these patients include complete host gene sequencing and microbiome sequencing of the stool and mucosa-associated microbiome. There would be technology and data available to decipher dysbiotic changes in host microbiome in context of host genetic makeup, and compute deficits or

Summary

Patients with Crohn's disease have decreased microbial diversity, which plays an important role in the pathogenesis of Crohn's disease. A better understanding of host-microbe interactions in patients with Crohn's disease is needed. Microbial restoration therapies are being studied for management of Crohn's disease and may be an adjunct to standard therapies in the future. It may be feasible to modify the gut microbiota community structure or function to treat patients with Crohn's disease with

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    Disclosure Statement: S. Khanna and L.E. Raffals have no relevant financial disclosures.

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