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Qualitative modelling of the interplay of inflammatory status and butyrate in the human gut: a hypotheses about robust bi-stability
School of Medical Health (MV), Örebro University, Örebro, Sweden.
Örebro University, School of Medical Sciences.ORCID iD: 0000-0003-3355-9452
Örebro University, School of Medical Sciences.ORCID iD: 0000-0003-3383-9219
Örebro University, School of Medical Sciences.ORCID iD: 0000-0001-8591-0799
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2018 (English)In: BMC Systems Biology, ISSN 1752-0509, E-ISSN 1752-0509, Vol. 12, no 1, article id 144Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Gut microbiota interacts with the human gut in multiple ways. Microbiota composition is altered in inflamed gut conditions. Likewise, certain microbial fermentation products as well as the lipopolysaccharides of the outer membrane are examples of microbial products with opposing influences on gut epithelium inflammation status. This system of intricate interactions is known to play a core role in human gut inflammatory diseases. Here, we present and analyse a simplified model of bidirectional interaction between the microbiota and the host: in focus is butyrate as an example for a bacterial fermentation product with anti-inflammatory properties.

RESULTS: We build a dynamical model based on an existing model of inflammatory regulation in gut epithelial cells. Our model introduces both butyrate as a bacterial product which counteracts inflammation, as well as bacterial LPS as a pro-inflammatory bacterial product. Moreover, we propose an extension of this model that also includes a feedback interaction towards bacterial composition. The analysis of these dynamical models shows robust bi-stability driven by butyrate concentrations in the gut. The extended model hints towards a further possible enforcement of the observed bi-stability via alteration of gut bacterial composition. A theoretical perspective on the stability of the described switch-like character is discussed.

CONCLUSIONS: Interpreting the results of this qualitative model allows formulating hypotheses about the switch-like character of inflammatory regulation in the gut epithelium, involving bacterial products as constitutive parts of the system. We also speculate about possible explanations for observed bimodal distributions in bacterial compositions in the human gut. The switch-like behaviour of the system proved to be mostly independent of parameter choices. Further implications of the qualitative character of our modeling approach for the robustness of the proposed hypotheses are discussed, as well as the pronounced role of butyrate compared to other inflammatory regulators, especially LPS, NF- κB and cytokines.

Place, publisher, year, edition, pages
BioMed Central, 2018. Vol. 12, no 1, article id 144
Keywords [en]
Bi-stability, Butyrate, Dynamical model, Dysbiosis, Gut microbiome, Inflammation, Short chain fatty acids
National Category
Gastroenterology and Hepatology Bioinformatics (Computational Biology)
Identifiers
URN: urn:nbn:se:oru:diva-70827DOI: 10.1186/s12918-018-0667-6ISI: 000453547300001PubMedID: 30558589Scopus ID: 2-s2.0-85058628095OAI: oai:DiVA.org:oru-70827DiVA, id: diva2:1273598
Funder
Knowledge Foundation, 20110225Available from: 2018-12-21 Created: 2018-12-21 Last updated: 2019-04-24Bibliographically approved

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Wall, RebeccaRangel, IgnacioMarques, Tatiana M.Repsilber, Dirk

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