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Emergence of microbial diversity due to cross-feeding interactions in a spatial model of gut microbial metabolism

Milan JA Van Hoek, View ORCID ProfileRoeland MH Merks
doi: https://doi.org/10.1101/059956
Milan JA Van Hoek
1Life Sciences Group, Centrum Wiskunde & Informatica, Science Park 123, 1098 XG Amsterdam, The Netherlands.
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Roeland MH Merks
1Life Sciences Group, Centrum Wiskunde & Informatica, Science Park 123, 1098 XG Amsterdam, The Netherlands.
2Mathematical Institute, Leiden University, Niels Bohrweg 1, 2333 CA Leiden, The Netherlands.
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  • ORCID record for Roeland MH Merks
  • For correspondence: merks@cwi.nl
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Abstract

Background The human gut contains approximately 1014 bacteria, belonging to hundreds of different species. Together, these microbial species form a complex food web that can break down food sources that our own digestive enzymes cannot handle, including complex polysaccharides, producing short chain fatty acids and additional metabolites, e.g., vitamin K. The diversity of microbial diversity is important for colonic health: Changes in the composition of the microbiota have been associated with inflammatory bowel disease, diabetes, obestity and Crohn’s disease, and make the microbiota more vulnerable to infestation by harmful species, e.g., Clostridium difficile. To get a grip on the controlling factors of microbial diversity in the gut, we here propose a multi-scale, spatiotemporal dynamic flux-balance analysis model to study the emergence of metabolic diversity in a spatial gut-like, tubular environment. The model features genome-scale metabolic models of microbial populations, resource sharing via extracellular metabolites, and spatial population dynamics and evolution.

Results In this model, cross-feeding interactions emerge readily, despite the species’ ability to metabolize sugars autonomously. Interestingly, the community requires cross-feeding for producing a realistic set of short-chain fatty acids from an input of glucose, If we let the composition of the microbial subpopulations change during invasion of adjacent space, a complex and stratifed microbiota evolves, with subspecies specializing on cross-feeding interactions via a mechanism of compensated trait loss. The microbial diversity and stratification collapse if the flux through the gut is enhanced to mimic diarrhea.

Conclusions In conclusion, this in silico model is a helpful tool in systems biology to predict and explain the controlling factors of microbial diversity in the gut. It can be extended to include, e.g., complex food source, and host-microbiota interactions via the gut wall.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted June 20, 2016.
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Emergence of microbial diversity due to cross-feeding interactions in a spatial model of gut microbial metabolism
Milan JA Van Hoek, Roeland MH Merks
bioRxiv 059956; doi: https://doi.org/10.1101/059956
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Emergence of microbial diversity due to cross-feeding interactions in a spatial model of gut microbial metabolism
Milan JA Van Hoek, Roeland MH Merks
bioRxiv 059956; doi: https://doi.org/10.1101/059956

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