Transient Colonising Microbes Promote Gut Dysbiosis and Disease Pathology

Species composition of the healthy adult gut microbiota tends to be stable over time. Destabilization of the gut microbiome under the influence of different factors is the main driver of the microbial dysbiosis and subsequent impacts on host physiology. Here, we used metagenomics data from a Swedish longitudinal cohort, to determine the stability of the gut microbiome and uncovered two distinct microbial species groups; persistent colonizing species (PCS) and transient colonizing species (TCS). We validated the continuation of this grouping, generating gut metagenomics data for additional time points from the same Swedish cohort. We evaluated the existence of PCS/TCS across different geographical regions and observed they are globally conserved features. To characterize PCS/TCS phenotypes, we performed bioreactor fermentation with faecal samples and metabolic modelling. Finally, using chronic disease gut metagenome and other multiomics data, we identified roles of TCS in microbial dysbiosis and link with abnormal changes to host physiology.

Funding Information: This study was supported by Engineering and Physical Sciences Research Council (EPSRC), EP/S001301/1, Biotechnology Biological Sciences Research Council (BBSRC) BB/S016899/1, Science for Life Laboratory (SciLifeLab), the Knut and Alice Wallenberg Foundation, and the Erling Persson Foundation. Additional funding was from the Metagenopolis grant ANR-11-DPBS-0001. DL and JP were supported by the Bio-Synergy Research Project (2012M3A9C4048758) of the Ministry of Science and ICT through the National Research Foundation. S.L. was supported by the Bio-Synergy Research Project (2021M3A9C4000991), the Basic Science Research Program (2021R1C1C1006336) and the Bio & Medical Technology Development Program (2021M3A9G8022959) of the Ministry of Science, ICT through the National Research Foundation, Korea; and supported by the '2020 Joint Research Project of Institutes of Science and Technology' at Korea; and supported by the GIST Research Institute (GRI) GIST-MIT research Collaboration grant and "GIST Research Institute (GRI) IIBR" with grants by the GIST in 2022.

Declaration of Interests: The authors declare no competing financial interests.

Ethics Approval Statement: All participants provided written informed consent. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki.

Keywords: Gut microbiome, Transient species, Dysbiosis, Gut stability, Multiomics

Suggested Citation: Suggested Citation

Lee, Sunjae and Meslier, Victoria and Bidkhori, Gholamreza and Etienne-Mesmin, Lucie and Park, Junseok and Plaza Onate, Florian and Cai, Haizhuang and Chatelier, Emmanuelle Le and Pons, Nicolas and Lee, Doheon and Proctor, Gordon and Mardinoglu, Adil and Blanquet-Diot, Stéphanie and Moyes, David L. and Almeida, Mathieu and Ehrlich, Stanislav Dusko and Uhlen, Mathias and Shoaie, Saeed, Transient Colonising Microbes Promote Gut Dysbiosis and Disease Pathology. Available at SSRN: https://ssrn.com/abstract=4163147 or http://dx.doi.org/10.2139/ssrn.4163147

This version of the paper has not been formally peer reviewed.