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An In Vitro Batch-culture Model to Estimate the Effects of Interventional Regimens on Human Fecal Microbiota

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Community metabolic modeling of host-microbiota interactions through multi-objective optimization.

Anna Lambert¹, Marko Budinich¹, Maxime Mahé^2,3,4

¹Nantes Université, École Centrale Nantes, CNRS, LS2N, UMR 6004, 44000 Nantes, France.

|July 2, 2024

Summary

Computational models reveal how gut microbes interact with intestinal cells. This study uncovers cross-feeding mechanisms, like choline exchange, and shows minimal microbial communities can support gut health.

Keywords:

microbiology microbiome molecular modeling

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Area of Science:

Microbiology
Computational Biology
Systems Biology

Background:

The human gut microbiota plays a crucial role in host health through complex microbial interactions.
Omics technologies link microbiome composition to health but often lack causal mechanistic insights.
Understanding these interactions is vital for deciphering host-microbe relationships.

Purpose of the Study:

To model and mechanistically understand metabolic interactions between gut microbes and host intestinal cells.
To develop a computational framework for predicting and quantifying microbial community dynamics.
To identify specific metabolic cross-feeding events driving symbiotic relationships.

Main Methods:

Utilized in silico genome-scale metabolic models (GEMs) to simulate microbial metabolism.
Applied multi-objective optimization to predict interactions among multiple organisms and an epithelial cell.
Developed a scoring system to quantify and classify inter-organismal interactions (competition, neutralism, mutualism).

Main Results:

Identified a potential choline cross-feeding interaction, explaining mutualism between Lactobacillus rhamnosus GG and intestinal epithelial cells.
The computational framework successfully predicted interaction types and strengths.
Analysis of a five-organism ecosystem demonstrated that a minimal microbiota can promote epithelial cell maintenance.

Conclusions:

In silico metabolic modeling provides a powerful approach to uncover causal mechanisms in host-microbiome interactions.
Choline cross-feeding is a key interaction supporting mutualism in the gut ecosystem.
Minimal microbial communities can be sufficient for maintaining intestinal epithelial cell health, challenging the notion that higher diversity is always necessary.