Metabolic network construction reveals probiotic-specific colonization resistance in a synthetic small intestinal community

The gut microbiota is essential to host health. Probiotics can be used as a microbiota targeted therapy to improve host health. However, probiotic molecular mechanisms of action and probiotics targeting the small intestinal microbiota are often not elucidated. In this study, we construct a three species synthetic community resembling the upper small intestine. We show that probiotic supplementation results in direct colonization resistance by affecting the metabolism of the community in a probiotic specific manner. Supplementation with Streptococcus thermophilus increased lactate production and reduced the pH, but did not affect the overall metabolic network substantially. In contrast, Lactobacillus casei did not alter lactate production or the pH, but increased the resistance to perturbations and nutrient utilization. Furthermore, supplementation of L. casei together with kynurenine increased metabolism along the kynurenine pathway and resulted in an elevated concentration of kynurenic acid, possibly leading to indirect colonization resistance. Together, we show how network construction can be used to improve the current or identify novel microbiota-targeted therapies.