title: Human Catestatin Alters Gut Microbiota Composition in Mice.
abstract: The mammalian intestinal tract is heavily colonized with a dense, complex, and diversified microbial populations. In healthy individuals, an array of epithelial antimicrobial agents is secreted in the gut to aid intestinal homeostasis. Enterochromaffin cells (EC) in the intestinal epithelium are a major source of chromogranin A (CgA), which is a pro-hormone and can be cleaved into many bioactive peptides that include catestatin (CST). This study was carried out to evaluate the possible impact of CST on gut microbiotain vivousing a mouse model. The CST (Human CgA352-372) or normal saline was intrarectally administered in C57BL/6 male mice for 6 days and then sacrificed. Feces and colonic mucosa tissue samples were collected, DNA was extracted, the V4 region of bacterial 16S rRNA gene was amplified and subjected to MiSeq Illumina sequencing. The α-diversity was calculated using Chao 1 and β-diversity was determined using QIIME. Differences at the genus level were determined using partial least square discriminant analysis (PLS-DA). Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) was used to predict functional capacity of bacterial community. CST treatment did not modify bacterial richness in fecal and colonic mucosa-associated microbiota; however, treatment significantly modified bacterial community composition between the groups. Also, CST-treated mice had a significantly lower relative abundance of Firmicutes and higher abundance of Bacteroidetes, observed only in fecal samples. However, at lower phylogenetic levels, PLS-DA analysis revealed that some bacterial taxa were significantly associated with the CST-treated mice in both fecal and colonic mucosa samples. In addition, differences in predicted microbial functional pathways in both fecal and colonic mucosa samples were detected. The results support the hypothesis that CST treatment modulates gut microbiota composition under non-pathophysiological conditions, however, the result of this study needs to be further validated in a larger experiment. The data may open new avenues for the development of a potential new line of antimicrobial peptides and their use as therapeutic agents to treat several inflammatory conditions of the gastrointestinal tract, such as inflammatory bowel disease (IBD), inflammatory bowel syndrome (IBS), or other health conditions.
authors.affiliation: Department of Immunology, University of Manitoba Winnipeg, MB, Canada.
authors.forename: Mohammad F
authors.initials: MF
authors.lastname: Rabbi
authors.affiliation: Department of Immunology, University of ManitobaWinnipeg, MB, Canada; Department of Animal Sciences, University of ManitobaWinnipeg, MB, Canada.
authors.forename: Peris M
authors.initials: PM
authors.lastname: Munyaka
authors.affiliation: Department of Immunology, University of Manitoba Winnipeg, MB, Canada.
authors.forename: Nour
authors.initials: N
authors.lastname: Eissa
authors.affiliation: Biomaterials and Tissue Engineering, Institut National de la Santé et de la Recherche Médicale Strasbourg, France.
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Metz-Boutigue
authors.affiliation: Department of Animal Sciences, University of ManitobaWinnipeg, MB, Canada; Department of Medical Microbiology, University of ManitobaWinnipeg, MB, Canada; The Children's Hospital Research Institute of ManitobaWinnipeg, MB, Canada.
authors.forename: Ehsan
authors.initials: E
authors.lastname: Khafipour
authors.affiliation: Department of Immunology, University of ManitobaWinnipeg, MB, Canada; The Children's Hospital Research Institute of ManitobaWinnipeg, MB, Canada; Section of Gastroenterology, Department of Internal Medicine, University of ManitobaWinnipeg, MB, Canada; Inflammatory Bowel Disease Clinical and Research Centre, University of ManitobaWinnipeg, MB, Canada.
authors.forename: Jean Eric
authors.initials: JE
authors.lastname: Ghia
keywords: antimicrobial peptides; catestatin (CST); chromogranin A (CgA); gut microbiota; intestinal homeostasis; microbial dysbiosis