Altered gut microbiota composition and function have been associated with inflammatory bowel diseases (IBD), including ulcerative colitis (UC). To date, there is no cure for UC and the cause remains unknown. Literature data have demonstrated both compositional and functional microbial changes in patients with IBD, but little is known about microbial composition or functional changes that occur prior to disease onset.
In order to shed light on this issue, Galipeau and colleagues applied 16S ribosomal RNA gene sequencing, shotgun metagenomic sequencing, functional assays, and mouse model to define the microbial composition and function in stool samples obtained from a cohort of healthy individuals at risk for inflammatory bowel diseases (pre-UC) who later developed UC (post-UC) and matched healthy control individuals (HCs).
The authors showed that microbiota composition of post-UC samples differed from HC and pre-UC samples. Metagenomic sequencing identified over 22,000 genes to be significantly different between HC, pre-UC and post-UC samples, of which 237 are protease- or peptidase-related. In addition, microbial function between pre-UC and HC samples is distinguished based on the protease- or peptidase-related genes.
To investigate a microbial contribution to the proteolytic signature, Galipeau and colleagues correlated elastase activity with bacterial taxa in HC and pre-UC participants. Results showed that elastase activity is inversely correlated with abundance of beneficial bacteria taxa Adlercreutzia and Akkermansia in pre-UC and post-UC samples. Anti-inflammatory and anti-microbal activityof these taxa is known and as well as their depletion in patients with IBD. Moreover, high elastase activity is directly correlated with abundance in taxa with known high proteolytic activity, such as Bacteroides vulgatus, in pre-UC sample compare to HC. Notably, Bacteroides vulgatus is increased in patients with active IBD.
Taken together, these results showed that fecal proteolytic activity could be used as a marker of UC progression or activation. In addition, the results achieved were also confirmed in a germ-free mouse model colonized with pre-UC and post-UC bacteria compared with HC.
In this study Galipeau and colleagues showed that differences in microbial function related to proteolytic activity are evident before the onset of clinically relevant disease in individuals at risk for IBD, who could develop UC. Although more studies are required to reveal the mechanism and the etiology of the disease, these data show that fecal proteolytic activity could be a biomarker to identify and monitor individuals at risk for UC.
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