Investigating Dysbiosis as a Cause and Predictor of Intestinal Pathology
Creators: name: Beamish, Emma
Publisher: name: Lancaster University
Year: 2017
Subjects: dysbiosis
microbiota
intestine
inflammatory bowel disease
ileostomy
diagnosis
Metabolomics
inflammation

description: Intestinal dysbiosis involves a shift in microbial composition and
      abundance within the gut and compelling evidence has highlighted the
      pivotal role dysbiosis plays in the onset and pathogenesis of numerous
      diseases, including inflammatory bowel disease (IBD), allergies and even
      mental health disorders. The intestinal microbiota is largely defined by
      host diet; a recent mouse model of total parenteral nutrition (TPN) showed
      that a dysbiotic shift in microbial dominance occurs following enteral
      nutrient depravation. Furthermore, metabolomics studies have identified
      that IBD patients can be discriminated from healthy based on their urinary
      metabolite profiles, but whether such profiles are accountable to
      intestinal dysbiosis remains uncertain. The research presented herein
      employed two human models; a novel TPN model in loop ileostomy patients,
      and patients with IBD, to assess microbial shifts and associated
      physiological consequences as well as determine whether urinary metabolite
      profiles are reflective of the intestinal microbiota.
      
      Using 16S rDNA-qPCR and -DGGE methods we revealed extensive variations in
      the microbiota of functional and defunctioned ileum following enteral
      nutrient deprivation, with a significant relative decrease in the
      Firmicutes phylum and concomitant increases in γ-Proteobacteria.
      Immunohistochemical techniques exposed a distinct physiological
      environment associated with a dysbiotic microbiota. Such environment was
      defined by reduced epithelial cell proliferation and mucosal atrophy that
      is likely due to altered host-microbiota interactions at the epithelial
      surface. We also observed post-operative complications that were
      potentially dysbiosis-mediated in almost 50% of the study cohort.
      
      Urinary NMR and Illumina 16S next-generation sequencing multi-omics
      statistical analyses identified correlations between dietary-associated
      urinary metabolites, particularly epicatechin, and distinct
      enterotype-like microbiota profiles. Application of this principle to
      prediction of IBD, as an example of a dysbiosis-associated disease, proved
      to be difficult due to limited sample numbers confounding interpatient
      variability.
      
      This research furthers the utilisation of intestinal microbiota as a
      therapeutic target, possibly via novel prebiotic administration to the
      defunctioned ileum with the potential to restore microbiota function prior
      to reanastomosis and reduce post-operative complications. Furthermore, it
      also provides promise for inexpensive, non-invasive detection of dysbiosis
      as a risk-factor of associated diseases. Further research, employing
      greater numbers of participants, is required to fully evaluate the
      potential predictive value of dysbiosis.