Systematic modelling: quantitative and semi-qualitative implementations of nutrition-microbe-gut-blood-brain interactions regarding the role of butyrate

A complex system of interactions links butyrate production by butyrate-producing bacteria, its transport into gut epithelial cells, its metabolism, protective effects with regard to oxidative stress and promotion of amino acid uptake, where the latter may explain effects on enteric nerve system and brain for example via tryptophane uptake and serotonin metabolism. Optimisation of a pre-biotic food approach for best possible butyrate-mediated effects regarding protection against oxidative stress, immune system balance, and positive effects on the nerve system, needs to take into account the complex structure of the existing interactions to find the appropriate approaches for monitoring, diagnosis of dysfunction, and possibilities to influence. This interaction structure needs therefore to be implemented as a concrete model, eligible to make predictions, and to systematically identify the most important knowledge gaps. Such a model is necessarily based to a large extent on soft data, calling for modern approaches of qualitative modelling, such as automated reasoning or fuzzy probabilistic modelling. These modelling approaches allow to deal with systems where the structure is to a large extent unknown, and mostly qualitative, as it is the case of the current butyrate system. Prior knowledge can be implemented as concrete as possible, and data from own experimental projects can then be understood on this background. As outcome of automated reasoning, parts of the system will be identified for which a systematic collection of data would lead to optimal improvement of predictability of the system. Moreover, system observables eligible for monitoring of system status, for example under therapy, or for influencing the system can be extracted. Identifiability analyses will give hint of those parts of the interaction system for which data at hand can lead to valuable predictions, and to identify new hypotheses to test in future experiments. Employing a qualitative modelling approach as coarsely outlined here, thus, would enable us to develop a controlled and systematic plan to collect, implement, and refine the understanding of the system of interactions that involve the mechanisms around butyrate functioning. This would lead to an efficient circle of research and model refinement.