top of page

Novel gut pathobionts confound results in a widely used model of human inflammatory disease

Forster et al. (BioRxiv) DOI: 10.1101/2021.02.09.430393

 

Keywords

  • DSS

  • Microbiome

  • Phenotypic heterogeneity

 

Main Findings​

Forster et al show that disease outcome following DSS treatment is highly variable and predicted by the differential presence of disease- and health-associated taxa in the steady state microbiome. The authors further characterise four (2 health- and 2 disease-associated) species through monocolonization experiments, showing that disease-associated Duncaniella muricolitica and Alistipes okayasuensis exacerbate weight loss, mortality and monocyte/macrophage colonic infiltrate following DSS treatment. These 2 species are found to be common, but not ubiquitous, in 31 animal facilities providing a rationale for the potential inclusion of these bacteria in monitoring regimes. The authors also document a lack of correlation between weight loss and histopathology, raising the importance of viewing these as independent parameters that do not serve as substitutes for one another in the DSS model. 

​

Limitations

  • 3 other disease-associated species identified by linear discriminant analysis of pre- and post-DSS microbiomes not characterised further or included in intra-institutional variation analysis.

  • Open question: unexplored mechanism by which D. muricolitica and A. okayasuensis influence disease severity. 

  • Open question: factor driving weight loss not identified or discussed further.

  • Both open questions tie into the unexplored observation that mice monocolonized with disease-associated, in comparison to those with health-associated, species demonstrate exacerbated weight loss and mortality but not colon or caecum histopathology following DSS treatment. 

​

Significance/Novelty

Forster et al identify two novel bacterial species which exacerbate disease parameters in DSS colitis. This work highlights the importance of microbiome reporting/monitoring in the DSS model with implications on results obtained and data interpretation. As the DSS model is used in pre-clinical trials, these implications extend to the development of IBD therapeutics. The finding that weight loss is not a readout for intestinal pathology is an important consideration for DSS study design.

​

Credit 

Reviewed by Rebecca Jeffery as part of the cross-institutional journal club of the Immunology Institute of the Icahn School of Medicine, Mount Sinai and the Kennedy Institute of Rheumatology, University of Oxford. Follow Rebecca on Twitter.

​

bottom of page