Remission in Crohn’s disease and relapses
People with Crohn’s disease (CD) in remission do not exhibit an improvement in gut microbiota composition, which might trigger relapses.
The present study investigated the dysbiosis and mucins production in CD patients during remission.
Crohn’s disease (CD) is characterized by chronic inflammation of the gastrointestinal (GI) tract, and is associated with an increase in the production of inflammatory cytokines, such as interleukins (IL) and tumor necrosis factor alpha (TNF-α)1. The disease involves complex interactions among the host immune system, intestinal mucosa and gut microbiota.
Interestingly, the gut microbiome has been receiving more attention, and is thought to play a more important role than previously thought2.
The colonic mucus barrier is considered the first line of defense against antigens and bacteria present in the intestinal lumen. It is composed of glycoproteins, trefoil factors and mucins6. In fact, it was previously reported that changes in the secretion patterns of mucins may be a primary event in CD or secondary to the observed inflammation7.
Two types of mucins produced by the GI tract include, neutral and acid. In the upper GI tract, neutral mucins are predominantly secreted, while acid mucins prevail in the colon5.
Additionally, studies have demonstrated that mucins content and expression are important for modulating short chain fatty acid (SCFA) synthesis, affecting the anti-inflammatory and immunological roles of these compounds3,4.
Despite the apparent importance of mucins in the GI tract, the role of these proteins during the CD remission phase has not yet been deeply investigated.
In CD, there are frequent relapses after periods of remission which are not entirely well understood. In fact, it is plausible that clinical remission is not accompanied by a reestablishment in the microbial balance of the GI tract, which might trigger future relapses.
The results of the present study demonstrated that the GI tract of CD patients in remission still display dysbiosis, that is characterized by reduced microorganism diversity. Additionally, there was an observed increase in the amount of Proteobacteria and a decrease in Verrucomicrobia. The CD group also presented increased mucins production.
According to Rothschild et al.21, individuals that experience the same environmental factors tend to have a similar gut microbiota compositions. Additionally, it is known that microbiota vary according to geography, cultural habits, age, and lifestyle factors that include diet, smoking, physical activity as well as others.
Thus, in order to avoid potential biases when comparing CD patients to control group all of the study subjects must be exposed to the same environment8,22,23,24. In the present study, our control group consisted of people who were considered healthy, resided in the same home, had a similar hygiene status, consumed identical diets, and were, in general, exposed to equivalent environmental and other common lifestyle factors that could influence the composition of the gut microbiota.
The inflammation caused by CD, frequently results in damage to the intestinal wall7. The colonic mucus barrier provides a protective layer against potential antigens, pathogenic bacteria and metabolites produced by microorganisms present in the intestinal lumen.
It is important to mention that individuals with CD produce higher levels of mucins, that could attenuate the inflammatory response. Interestingly, the results herein showed that, even during remission CD patients also exhibit augmented mucin production, despite most of these patients not displaying any signs of inflammation, as revealed through colonoscopies.
The CD group during remission presented a different gut microbiota when compared to both the healthy subjects (HS) and patients with active CD, apparently representing an intermediate microbiota composition.
In addition, a previous study reported that CD patients also have higher proportions of fungi in their intestines, with increased C. albicans and decreased S. cerevisiae content28. Herein we showed that CD patients in remission have reduced S. cerevisiae levels when compared with the control group. This result is similar to what has been observed in patients with active CD29. This is also relevant to inflammation, since a previous study with mice demonstrated that S. cerevisiae supplementation promoted a significant reduction in TNF-α expression and an increase in IL-10 production30. Through this anti-inflammatory effect S. cerevisiae can contribute to the regulation of the inflammatory process in patients with CD29, and its reduced presence may make these individuals more susceptible to relapses.
In conclusion, during remission CD patients present increased amounts of the neutral and acid mucins that are accompanied by a global dysbiosis.
Read full study here.