Crohn’s Disease (CD) is one of the sets of inflammatory bowel disease (IBD) that consists of chronic inflammation of the terminal ileum, that can extend throughout the gastrointestinal tract. Researchers have focused more on the role the gut microbiota plays in CD over the years to better understand disease progression. Increased endotoxemia, inflammation, fungal loads and changes in the gut microbiota composition, as well as altered mucins production have been observed in CD patients compared to healthy populations.
CD patients often suffer from bouts of relapse after being in remission, yet their causes are not fully understood. Therefore, a new cross-sectional single center study published in Scientific Reports investigated alterations in the fecal microbiota composition and mucins expression patterns in healthy controls versus CD patients in remission; remission was defined according to the Crohn’s Disease activity score (CDAI) score which assesses and quantifies disease progression based on a scale of 0-600. A score less than 150 represents inactive disease whereas more than 450 indicates severe disease.
The authors analyzed 18 CD patients and 18 healthy controls in Brazil for one year. Since environmental and lifestyle factors greatly impact the gut microbiota composition, the CD patient and healthy control pairs lived in the same home and were exposed to similar environmental, hygienic and dietary conditions in order to avoid potential biases when comparing CD patients and healthy controls.
The authors discovered that CD patients in remission had a lower α-diversity compared to healthy controls, greater abundance of the Proteobacteria phylum and lower Deltaproteobacteria class abundance. CD patients in remission also had reduced abundances of Akkermansia and Oscillospira genera, the yeast Saccharomyces cerevisiae, and sulfate-reducing bacteria.
CD patients often suffer from damage to the intestinal barrier. Bacteria belonging to Akkermansia and Oscillospira genera degrade mucins, and reductions of these genera have been associated with increased intestinal permeability which could trigger metabolic endotoxemia and other conditions like IBD. Moreover, S. cerevisiae has been found in increased abundance in non-inflamed mucosa of CD patients and may also benefit the host through its anti-inflammatory properties. For example, S. cerevisiae has been shown to reduce inflammatory markers such as tumor necrosis factor alpha (TNF- α) expression in mice. Studies have reported TNF- α to be a key driver of inflammation in IBD patients. Additionally, sulfate-reducing bacteria, which are members of the Desulfovibrio genus in the Deltaproteobacteria class, reduce sulfate to hydrogen sulfate for energy production which can trigger cell damage and even death in human intestinal epithelial cells, thereby damaging the intestinal barrier.
In line with these findings, CD patients in remission also had increased neutral and acid mucin concentrations. Goblet cells in the intestines produce mucins that prevent bacteria from entering into the intestinal lumen and also regulate the synthesis of anti-inflammatory short-chain fatty acids. The authors hypothesized that the decreased abundance of mucin degrading bacteria and the anti-inflammatory yeast S. cerevisiae observed in the CD remission patients may have led to increased mucins production that could have served as a protective mechanism against recurrence of inflammation Additionally, the authors of this study did not observe significant shifts in the beneficial bacteria Faecalibacterium prausnitzii, which has been reported to be in lower abundances in CD patients who present low grade inflammation.
Despite the study’s limitations of being an observational study that analyzed only one yeast species and did not investigate patients with active CD, the authors reported novel findings of increased mucins production and an imbalanced gut microbiome in CD patients in remission. While the causes of periods of relapses and remissions many CD patients experience are still not fully understood, the authors speculate that these patients likely do not experience a full restoration of microbial balance which leads to future relapses. More studies are needed to better understand the role mucins production, the gut microbiota, and fungi play in CD disease progression and relapse.
Reference: Magro DO, Santos A, Guadagnini D, et al. Remission in Crohn’s disease is accompanied by alterations in the gut microbiota and mucins production. Scientific Reports, 2019. doi:10.1038/s41598-019-49893-5 https://www.nature.com/articles/s41598-019-49893-5?fbclid=IwAR1lWzGBGHCNVTXXmB5te9aCQA91N4AXocGDLNyRLS4S-B0xKmxe5l4BMAY