The Effect of Gut Microbiota Dysbiosis on Malnourishment

The human gut hosts a remarkable number of microbial cells. The gut microbiota plays a significant role in maintaining human health by performing different metabolic tasks such as digestion of dietary components that are indigestible for the human body as well as secretion of valuable metabolites such as short-chain fatty acids, vitamins and essential amino acids. There is growing evidence that dysbiosis of the gut microbiota is associated with a wide range of disorders such type 2 diabetes, obesity and cardiovascular diseases [1]. These findings render the systemic analysis of the human gut microbiota alterations crucial in order to understand its potential role in disease onset and progression.

GEnome-scale Metabolic models (GEMs) have been used to gain a deeper understanding of the interplay between genotype and phenotype [2]. In this study, GEMs for the most abundant bacteria in the gut microbiota of the healthy and malnourished children [3-5], will be reconstructed and thoroughly curated. The functionally of the models will be validated using different experimental data. After the reconstruction of the high-quality models for the representative bacteria, the interactions between the bacteria within the microbial community as well as their interaction with the host and diet will be simulated using a previously developed toolbox, CASINO [6] (Community and Systems-level Interactive Optimization). CASINO takes into account the tendency of each bacteria species to maximize its growth as well as the optimality of the microbe-microbe interactions and resource distribution in the community. Once the optimality of the community is achieved, the production rate of amino acids and vitamins will be quantified, and eventually metabolic differences between the healthy and malnourished children will be identified. Studying the dysbiosis of microbial communities in two different conditions through mathematical models will help us to reveal the relationships between the composition of the gut microbiota and malnourishment.

1.         Karlsson, F., et al., Assessing the human gut microbiota in metabolic diseases. Diabetes, 2013. 62(10): p. 3341-3349.

2.         Shoaie, S., et al., Understanding the interactions between bacteria in the human gut through metabolic modeling. Scientific reports, 2013. 3.

3.         Subramanian, S., et al., Persistent gut microbiota immaturity in malnourished Bangladeshi children.Nature, 2014.

4.         Smith, M.I., et al., Gut microbiomes of Malawian twin pairs discordant for kwashiorkor. Science, 2013. 339(6119): p. 548-554.

5.         Bäckhed, F., et al., Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life. Cell host & microbe, 2015. 17(5): p. 690-703.

6.         Shoaie, S., et al., Quantifying diet-induced metabolic changes of the human gut microbiome. Cell Metabolism, 2015. in press