Gut microbiota and the ‘inflammatory loop’ in IBD: Interview with Prof. Harry Sokol

IBD - Inflammatory Bowel Disease

IBD – Inflammatory Bowel Disease

Understandings of inflammatory bowel disease (IBD) have advanced in recent years, informed by studies that have investigated the role of the gut microbiota in disease pathogenesis and progression. Prof. Harry Sokol is a gastroenterologist and researcher from France who has participated in this pioneering work. At the Gut Microbiota for Health World Summit 2016 in Miami, Sokol took the time to speak with GMFH editors.

When you first started to investigate the gut microbiota in IBD, what did you find?

We saw that gut microbiota of IBD patients was ‘dysbiotic’—the composition was different from healthy subjects. Notably, we saw that one bacterium, Faecalibacterium prausnitzii, was particularly decreased in IBD patients.

We also had a study at this time on patients with Crohn’s disease who underwent surgery. The surprise of this study was that the level of F. prau was correlated with the relapse risk—that is, patients with low levels of the bacteria [had a] higher risk of relapse. So we hypothesized that these bacteria could have anti-inflammatory effects. We did some in vitro and in vivo work in mice, and we confirmed that this was true.

It was quite a new concept at this time because it was, to my knowledge, the first time someone showed that an intestinal bacteria involved in dysbiosis in humans could have effects on the host.

Currently, how do you understand the role of the gut microbiota in IBD?

For a long time, one question was whether dysbiosis was the chicken or the egg. Now we have a lot of data showing that the microbiota by itself plays a role in the disease. Of course you need some genetic predisposition—but you also need environmental factors that will shape the microbiota in an abnormal way.

This abnormal microbiota itself plays a role in the inflammation process: either as a trigger or to increase or sustain the inflammation. It’s a kind of vicious cycle, because you have host factors and environmental factors that will have effects on the microbiota and possibly initiate inflammation, but then the microbiota become abnormal and play a role in the inflammatory loop. So dysbiosis is not chicken or egg, it’s both.

How might the gut microbiota differ in Crohn’s disease and ulcerative colitis?

Recently published data support the fact that ulcerative colitis is different from Crohn’s disease. Moreover, Crohn’s disease itself is heterogeneous, notably when patients are separated according to the involvement of the small bowel. This means Crohn’s disease patients with involvement of the small bowel are completely different from the ones without it. We see this at the bacterial microbiota level, but also at the fungal microbiota level. We just published a paper in Gut on the fungal microbiota in IBD and we see that it’s different based on the ileal involvement status. It has also been shown that the genetics are different between Crohn’s disease with and without ileal involvement. Does the microbiota by itself play a role in this different phenotype? We don’t know, but it’s very possible.

It’s also very possible that, because of the genetics, which are different if you have Crohn’s disease or ulcerative colitis, you will shape a different microbiota and this will also play a role in the phenotype.

What do you see as the future of fecal microbiota transplantation (FMT) for IBD?

Currently, the only setting in which FMT is really effective is for recurrent C. difficile infection.

Regarding IBD, we have some studies available, but we cannot make a conclusion on the effect of FMT in IBD. One of the problems is that there are different ways of doing FMT: fresh, frozen, upper GI, lower GI… FMT is quite a complicated treatment because of logistics, and also because of the fact that we really don’t know what we are doing. The microbiota is a kind of ‘black box’—we take it, we do some analyses, but obviously we don’t really know what’s in it, and we give it to a patient.

Also, now that we know the microbiota plays a role in plenty of different diseases, it is possible that transferring the microbiota could also have some damaging effects in the long term: obesity, cancer, and more. Even if FMT is effective in IBD, which is not yet proven, I think that it will be only transient treatment, a temporary treatment. We will have to move to more controlled systems, such as either next-generation probiotics or consortia of intestinal bacteria, instead of complex microbiotas that we do not really control.

To achieve this aim, we need to do FMT trials. Because if we analyze the microbiota of the donor and of the recipient, we have a chance to identify the microorganisms that play a role in the effect. We have to do FMT trials now, so we [can] move from FMT to more controlled settings later.

Kristina Campbell
Kristina Campbell
Science writer Kristina Campbell (M.Sc.), from British Columbia (Canada), specializes in communicating about the gut microbiota, digestive health, and nutrition. Author of the best selling Well-Fed Microbiome Cookbook, her freelance work has appeared in publications around the world. Kristina joined the Gut Microbiota for Health publishing team in 2014.  Find her on: GoogleTwitter