(194j) Byproduct Cross Feeding and Community Stability in an in silico Biofilm Model of the Gut Microbiome

The Human Microbiome Project was launched in 2008 with the goal of developing improved understanding of the human microbiome and its role in human health and disease. To date, the most widely studied system is the gut microbiome due to its critical role in food metabolism, profound influence on the immune system and suspected role in a wide variety of diseases including gut infections, inflammatory bowel and Crohns diseases, obesity, diabetes, cardiovascular disease, rheumatoid arthritis, colorectal cancer and even depression. The human gut microbiome is a highly complex multispecies system thought to consist of at approximately 1,800 genera and 15,000-36,000 species of microbes. The two dominant phyla in healthy humans are Firmicutes and Bacteroidetes, which comprise more than 90% of the community. Other important but much less prevalent phyla are Proteobacteria, Actinobacteria, Euryarchaeota and Verrucomicrobia as well as Eukaryota such as fungi. A critical metabolic function of the gut microbiota is to convert dietary fiber into short-chain fatty acids (SCFAs) that can be absorbed by the host intestine as an energy source.

Gut microbiome function is usually robust to dietary changes and other perturbations that alter species composition and SCFA synthesis. Correspondingly, metagenomic studies have shown wide variations in microbiota diversity and composition within healthy human populations. However, large perturbations in susceptible individuals can result in long-term microbiome alteration. Many diseases are associated with the gut flora being perturbed from their normal state through a poorly understood process known as dysbiosis. The role of species interactions in maintaining healthy community function or promoting dysbiosis are poorly understood. Despite some recent progress, the types of species interactions required for stable community dynamics in biofilm communities where nutrient gradients provide niches for different metabolic lifestyles have not been elucidated.

We developed a biofilm metabolic model of a very simple gut microbiome community consisting of a representative bacteroidete (Bacteroides thetaiotaomicron), firmicute (Faecalibacterium prausnitzii) and proteobacterium (Escherichia coli) to investigate the putative role of metabolic byproduct cross feeding between species on community stability, robustness and flexibility. The model predicted co-existence of the three species only if four essential cross-feeding relationships were present. We found that cross feeding allowed co-existence to be robustly maintained for large variations in biofilm thickness and nutrient levels. Our model predictions provide new insights into the impact of byproduct cross feeding and yield experimentally testable hypotheses about gut microbiome community stability.