Microbiota and Crohn’s Disease

Recent advances have enabled more meticulous investigations into intestinal microbiota compositions, which affect both the onset and degree of severity in Crohn’s disease (CD). A 1970 study by Mitchell and Rees explored the effects of injecting homogenates isolated from patients with and without CD into mice. Mice who were injected with the Crohn’s homogenates developed symptoms similar to human characteristics of the disease, indicating that there is an “agent” that can be transmitted from one organism to another. Because some homogenates were taken from the intestine, the agent(s) could be members of the gut flora community (Mitchell and Rees, 1970).

Mitchell and Rees noted that no mycobacteria were isolated from any samples. However, in 1984, researchers were able to isolate a species of mycobacterium from gastrointestinal samples of CD patients. Not only were they able to record the presence of mycobacterium in the isolates, but they also conducted an experiment that demonstrated that granulomas form in goats when inoculated with the Mycobacterium species. This links to the transmissible agent that Mitchell and Rees posited and suggests a causative role in at least some cases of CD (Chiodini et al., 1984).

Starting in the late 2000s, deeper research into how microbiota composition and CD may be related began and was enabled by technological advances implemented in the field on microbial ecology. Joossens, et.al. used denaturing gradient gel electrophoresis (DGGE) to develop a dysbiosis signature that is similar across patients with Crohn’s. Levels of five bacterial species, Dialister invisusFaecalibacterium prausnitziiBifidobacterium adolescentisRuminococcus gnavus, and an uncharacterized species of Clostridium cluster XIVa, were consistently altered in the microbiome of patients with CD, comprising a dysbiosis signature. The authors also found that the gut microbiota populations were different in healthy relatives of those with CD compared to individuals with no familial history of CD (Joossens et al., 2011). A 2014 study by Gevers, et.al. supported and furthered this notion by identifying species with elevated or diminished populations and demonstrating that dysbiosis in patients with Crohn’s increased when antibiotics were given (Gevers et al., 2014).

Varied populations of intestinal microbiota. Adapted from Gevers, et.al, 2014).

Vandeputte, et.al. developed a unique method of quantitative microbiome profiling in 2017 that enabled specific counts of microbial populations whereas previous studies relied on comparative analyses. As the researchers state, “comparative analyses of relative microbiome data cannot provide information about the extent or directionality of changes in taxa abundance or metabolic potential,” which their technique can do (Vandeputte et al., 2017). Overall, they found that microbial counts were overall lower in stool samples of those with CD and levels of Bacteroides bacteria were particularly low, consistent with other studies.

A 2018 Nature Paper provided a link between microbiota composition and NOD2, a protein involved in innate immunity.  They found that when NOD2-deficient mice are housed with Nod2+/+ mice, gut microbiota composition in the neighboring mice was affected; it lead to an increase in beneficial bacteria and immune cells in Nod2+/+ mice, while exposure to Nod2+/+ mice lead to acquisition of potentially harmful bacteria in NOD2-deficient mice, exacerbating inflammatory symptoms (Butera et al., 2018).

Through sequencing of 16S rRNA, quantification via Q-RT-PCR, and identification of biochemical profiles of the bacteria, researchers have complied profiles of the microbiota that inhabit both diseased and healthy GI tracts. Complete profiling is necessary to investigate the mechanisms of CD and thus possible modes of therapy.


Butera, A., Paola, M.D., Pavarini, L., Strati, F., Pindo, M., Sanchez, M., Cavalieri, D., Boirivant, M., Filippo, C.D., 2018. Nod2 Deficiency in mice is Associated with Microbiota Variation Favouring the Expansion of mucosal CD4+ LAP+ Regulatory Cells. Nature 8, 14241. https://doi.org/10.1038/s41598-018-32583-z

Chiodini, R.J., Van Kruiningen, H.J., Merkal, R.S., Thayer, W.R., Coutu, J.A., 1984. Characteristics of an unclassified Mycobacterium species isolated from patients with Crohn’s disease. J Clin Microbiol 20, 966–971.

Gevers, D., Kugathasan, S., Denson, L.A., Vázquez-Baeza, Y., Van Treuren, W., Ren, B., Schwager, E., Knights, D., Song, S.J., Yassour, M., Morgan, X.C., Kostic, A.D., Luo, C., González, A., McDonald, D., Haberman, Y., Walters, T., Baker, S., Rosh, J., Stephens, M., Heyman, M., Markowitz, J., Baldassano, R., Griffiths, A., Sylvester, F., Mack, D., Kim, S., Crandall, W., Hyams, J., Huttenhower, C., Knight, R., Xavier, R.J., 2014. The Treatment-Naive Microbiome in New-Onset Crohn’s Disease. Cell Host & Microbe 15, 382–392. https://doi.org/10.1016/j.chom.2014.02.005

Joossens, M., Huys, G., Cnockaert, M., Preter, V.D., Verbeke, K., Rutgeerts, P., Vandamme, P., Vermeire, S., 2011. Dysbiosis of the faecal microbiota in patients with Crohn’s disease and their unaffected relatives. Gut 60, 631–637. https://doi.org/10.1136/gut.2010.223263

Mitchell, D.N., Rees, R.J., 1970. Agent transmissible from Crohn’s disease tissue. Lancet 2, 168–171.

Vandeputte, D., Kathagen, G., D’hoe, K., Vieira-Silva, S., Valles-Colomer, M., Sabino, J., Wang, J., Tito, R.Y., De Commer, L., Darzi, Y., Vermeire, S., Falony, G., Raes, J., 2017. Quantitative microbiome profiling links gut community variation to microbial load. Nature 551, 507–511. https://doi.org/10.1038/nature24460

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