In inflammatory bowel disease (IBD), a set of conditions that includes Crohn’s disease and ulcerative colitis (UC), parts of the digestive tract become chronically inflamed. ‘Debilitating’ doesn’t begin to describe IBD at its most intense: during a disease flare, someone who normally leads a busy and active life may have to put everything on hold to stay at home, close to the bathroom, battling pain and nausea.
Genes are only one part of how IBD arises. The other parts are less clear, but equally important in the quest to understand how to prevent and treat these conditions. A new report, Gut microbiota and inflammatory bowel disease, published by the Gut Microbiota for Health Experts Exchange platform and edited by Professors Philippe Marteau and Harry Sokol, gives an overview of the new theories on the disordered physiology of IBD. These theories allow for at least three other influencing factors besides genes – the gut microbiota, the immune system and outside (or environmental) elements. It may therefore be that a perfect storm made up of all these factors manifests itself as inflammatory bowel disease.
At the centre of this discussion is an intriguing observation scientists have made: when you take a detailed look at the digestive tracts of people with Crohn’s disease and UC, the bacterial composition differs from that of a completely healthy person. Most notably, there is a smaller population of a particular anti-inflammatory bacteria (the awkwardly named Faecalibacterium prausnitzii). Not only that, but also the community of resident viruses is distorted compared to a healthy person.
These differences in microbial communities (sometimes called ‘signatures’) may or may not cause IBD, but at the very least they could lead to new understandings of what is happening when symptoms occur. The signatures are now best understood as flags that identify a microbial landscape as one associated with disease, even though that landscape is still incompletely mapped.
In addition to the microbiota, two related factors may play a role in inflammatory bowel disease: the immune system and environmental triggers. The immune system may have been ‘educated’ in a way that leaves the body less able to fight inflammation by itself. Meanwhile, clues to environmental triggers can be found by looking back at what has happened in the lives of people diagnosed with IBD – for example, whether a person had many courses of antibiotics as a child. However, healthy adults and children cannot be subjected to these suspected triggers on purpose, thus limiting the potential for research. Interestingly, scientific discussion acknowledges that the gut microbiota is known to interact with both the immune system and environmental influences and that these two factors may ultimately act through their disruption of intestinal microbes and the metabolites they produce.
If gut microbiota has something to do with IBD, it makes sense that doctors would want to modify the bacteria to see if this improves patients’ symptoms. Probiotics are promising as a treatment strategy, as studies show they can dampen inflammation, modulate immunity and enhance digestive health. But administering a single probiotic strain is no match for the thriving, established community of microorganisms in the digestive tract of someone with IBD. A new challenge in medical practice therefore lies in how to modify the entire microbial community in a way that lasts.
Faecal microbiota transplantation (FMT) attempting to replace the whole community at once by receiving a donor’s fecal sample – is an area of active investigation. So far, though, it is no silver bullet. The few valid FMT trials (here and here) show that not all patients respond to FMT and that for those who do respond, repeated treatments are required. Furthermore, for some unknown reason, samples from certain donors work far better than those from other donors who are in apparently perfect health. Researchers therefore need to learn how to modify the transplantation procedure to make it ‘stick’ – probably by delivering synthetic combinations of microorganisms that imitate a healthy microbiota. First, though, they must learn much more about how microbial communities work.
More and more people experience the pain of IBD, as the disease’s prevalence is rising worldwide. But as gut microbiota research advances, there is more hope than ever that medicine will offer new options for those living with these diseases.
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