Document Type

Article

Publication Date

1-21-2020

Publication Title

mSystems

Keywords

flux balance analysis; gut microbiome; metagenome; systems biology

Abstract

Compositional changes in the gut microbiota have been associated with a variety of medical conditions such as obesity, Crohn's disease, and diabetes. However, connecting microbial community composition to ecosystem function remains a challenge. Here, we introduce MICOM, a customizable metabolic model of the human gut microbiome. By using a heuristic optimization approach based on L2 regularization, we were able to obtain a unique set of realistic growth rates that corresponded well with observed replication rates. We integrated adjustable dietary and taxon abundance constraints to generate personalized metabolic models for individual metagenomic samples. We applied MICOM to a balanced cohort of metagenomes from 186 people, including a metabolically healthy population and individuals with type 1 and type 2 diabetes. Model results showed that individual bacterial genera maintained conserved niche structures across humans, while the community-level production of short-chain fatty acids (SCFAs) was heterogeneous and highly individual specific. Model output revealed complex cross-feeding interactions that would be difficult to measure

Clinical Institute

Digestive Health

Department

Institute for Systems Biology

Department

Gastroenterology

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