The influence of gut bacteria on certain diseases
A comparative study of the gut microbiota in immune-mediated inflammatory diseases-does a common dysbiosis exist? Forbes JD*, Chen CY*, Knox NC*, Marrie RA, El-Gabalawy H, de Kievit T, Alfa M, Bernstein CN, Van Domselaar G*. Microbiome 2018 Dec 13; 6(1):221. doi: https://doi.org/10.1186/s40168-018-0603-4
This science story details the collaborative publication on gut microbiota in relation to immune-mediated inflammatory diseases (IMIDs). The use of modern genome-based sequencing coupled with a machine learning approaches is an example of using advanced technologies to provide new information to help understand and address clinical and public health issues.
What was known about this area prior to your work, and why was the research done?
Rheumatoid arthritis (RA), multiple sclerosis (MS), and inflammatory bowel diseases (IBD) including Crohn’s disease (CD) and ulcerative colitis (UC) are among the most familiar examples immune-mediated inflammatory diseases (IMIDs). IMIDs share common inflammatory pathways, but are otherwise seemingly unrelated and have no known cause. The human microbiome, which is the microbial community inhabiting the human body, is thought to play an important role in human health and disease, and influences human hormonal, metabolic, and immunological function. Shifts in the composition of the human gut microbiome can have health impacts and are known to occur in patients with IBD, although whether these shifts (referred to as dysbiosis) are a cause or consequence of the disease remains unknown. Studies are now emerging that report an association of a dysbiotic gut microbiome with IMIDs other than IBD. Such findings beg the question: is there a component of the gut microbial community composition that is common to some or all IMIDs? To answer this question, we performed a pilot study using 16S ribosomal RNA gene amplicon sequencing alongside a machine learning algorithm to compare the gut microbiota of people with CD, UC, MS, and RA, to each other and to healthy controls.
What are your most significant findings from this work?
Using differential abundance testing and machine learning (two distinct but complementary analytical approaches), we found several significant differences in bacterial taxa in the microbiota between IMID guts and healthy controls. Specifically, we found that all of our disease cohorts, when analyzed together in a single group, had significantly higher abundances of Actinomyces, Eggerthella, Clostridium III, Faecalicoccus and Streptococcus, relative to healthy controls. From a public health perspective, increases in particular species with known pathogenic potential, or alternatively, decreases in species that confer specific health benefits on the host may offer future therapeutic options. This finding is consistent with those reported in gut microbial community studies that have investigated the link between the gut microbiome and individual IMIDs. Further, we found several bacterial taxa that are discriminatory for each individual IMID versus healthy controls and versus each other. Interestingly, among all the IMIDs studied, we found that UC and CD have the biggest difference in gut microbial community structure, despite these diseases both preferentially targeting the gastrointestinal system. This finding suggests that while CD and UC are seemingly more related from a clinical perspective, they are distinct diseases. Lastly, epidemiologic data suggests that there is increased risk of developing a second IMID, such as MS or RA, in the presence of IBD. The common dysbiosis in microbiota profiles that we report might be associated with this phenomenon.
What are the implications or impact of the research?Although prior research links gut microbiome dysbiosis and specific IMIDs, our study is the first to collectively analyze multiple IMIDs to look for commonalities or differences in their gut microbial community profiles. Despite our modest cohort sizes (around 20 patients per disease), our findings are significant and consistent with the scientific literature for microbiome studies targeting individual IMIDs. Further, the corroborating results of our independent analytical approaches strengthen and support the validity of our findings. The bacterial taxa we found may serve as non-invasive diagnostic biomarkers for IMIDs and may help monitor disease severity, treatment response, or therapeutic intervention if further research shows these taxa as the causative agents of the IMIDs.
Additional References of Significance:
- Forbes J*, Van Domselaar G*, Bernstein CN. The gut microbiota in immune-mediated inflammatory diseases. Front Microbiol 2016 Jul 11; 7:1081 doi: https://doi.org/10.3389/fmicb.2016.01081
- Round JL, Palm NW. Causal effects of the microbiota on immune-mediated diseases. Sci Immunol 2018 Feb 9; 3(20). doi: https://doi.org/10.1126/sciimmunol.aao1603
- Knox NC*, Forbes JD*, Van Domselaar G*, Bernstein CN. The gut microbiome as a target for IBD treatment: Are we there yet? Curr Treat Options Gastroenterol 2019 Jan 19. doi: https://doi.org/10.1007/s11938-019-00221-w
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