The Gut Microbiome

Inflammatory Bowel Disease

The microbiome is hugely important to human health, and has been shown to beneficial to digestion, the immune system and even our mental health when in good working condition. However, disruption to the balance of the microbial flora has likewise been associated with multiple diseases and poor general health. Dysbiosis, or a poor balance, of human microbiome communities has been implicated in a wide range of disease, such as cardiovascular disease, chronic inflammation, obesity and even mental health issues. A diverse and well-balanced microbial community is important for disease prevention, however modern over usage of antibiotics as well as poor diets low in dietary fibre and high in artificial additives can lead to compromised communities dominated by single pathogenic strains of bacteria.

The human microbiome plays a critical role in overall health, from providing valuable metabolites to aiding the immune system. Friendly commensal bacteria colonise major regions in our gut, with characteristic diverse communities of microbes inhabiting them. These microbes occupy these niches and outcompete pathogenic organisms, actively preventing infection and disease.

In this article we will be specifically looking into the link between the gut microbiome and Inflammatory Bowel disease (IBD), as this is currently one of the most well researched cases of a causal relationship between the microbiome and disease state.

Dysbiosis and Disease state

Disruption of the gut flora is associated with painful inflammation of the gastrointestinal tract, diagnosed as IBD. Crohn’s disease and Ulcerative Colitis are conditions under the umbrella term of IBD and cause painful swelling and eventually ulcers in the gastrointestinal tract. The exact cause of IBD remains unclear, with the true cause likely a combination of genetics, environmental factors and the gut microbiome. Evidence has come to light that shows a link between disease state and the gut dysbiosis, where they influence each other and are potentially both each other’s cause and effect.

Successfully treating IBD has proved difficult; medications focus on alleviating inflammation or other symptoms as antibiotics have shown limited effectiveness in curing the disease. Antibiotics have even been suggested to weaken the immune system long-term, as evidence suggests that antibiotic clearance of commensal bacteria can provide opportunity for pathogenic strains to establish themselves. Medical treatments destabilizing the microbiome can lead to a change in overall metabolism and chronic Clostridium difficile infection. When colonization resistance is compromised there is more opportunity for single bacteria to dominate the community, with antibiotic-associated diarrhoea a common side effect associated with antibiotic induced dysbiosis.

Microbial based therapies

Recently potential therapies pivoted to target the microbiota, as reinstating a healthy colony of gut microbials should alleviate the cause of IBD. Previous treatments relied on antibiotics followed by a course of probiotics; however, this has had variable levels of success as the antibiotic treatment can further reduce bacterial diversity in the gut. Probiotics have limited effectiveness in alleviating symptoms; any effect is transient as no probiotic microbial strains are detectable after 2 weeks of stopping intake.

In modern clinical trials we have already seen positive results from microbiome treatments in clearing C. difficile infection, such as faecal microbiota transplantation (FMT) therapy. FMT uses faeces from a healthy donor, which are processed and delivered to the gastrointestinal tract of patients. Faeces contain a high microbial load, with up to 1011 bacterium per gram and multiple archaea, fungi and viruses that could not be delivered orally in a probiotic form. Success in resolving dysbiosis through FMT is variable but shows more promise than other therapies.

Future Potential

Specific forms of IBD such as ulcerative colitis (UC) was first treated with FMT in 1989, with patients reducing medications within a week of enema treatments and remaining clinically disease free for multiple years after treatment. More recent trials have had more variable levels of remission, suggesting donor compatibility, disease prevalence and engraftment of the microbiota all factor into the success of FMT. There is potential in this therapy, as FMT has proved more robust than previous treatments for IBD. Modern research into the relationship between disease and gut flora has come a long way in a relatively short time and shows there is much potential for future research in this area.

Written by Charlotte Jones

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