Manish Kumar, Boyang Ji, Parizad Babaei, Jun Geng, Adil Mardinogulu, & Jens Nielsen*, representing the Healthy Birth, Growth and Development knowledge integration (HBGDki) community
Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden
Objectives: Recent metagenomics studies have shown strong associations between the alteration of gut microbiota and children malnutrition [1,2]. However, precise mechanisms governing metabolic transition in the gut stimulated by the intestinal microbiota during health and malnutrition is unclear. Genome-scale metabolic reconstructions and their analysis with constraint-based modeling techniques are natural next steps after sequencing of a genome to link top-down systems biology analyses at genome scale with bottom-up systems biology modeling. In this study, we have employed genome scale metabolic modeling to understand the metabolic variations in gut microbiota of children during health and malnutrition.
Methods: To quantify the contribution of gut microbiota to the metabolic differences between health and malnutrition of children, we have reconstructed genome scale metabolic models (GEMs) for 52 species, which represent the 20 most abundant species in the gut microbiota of malnourished (Bangladeshi and Malawi) and healthy (Swedish, Bangladeshi, and Malawi) children [1–3]. With these GEMs, we inferred the metabolic signatures of the most abundant gut bacterial species, which provide the basis for analysis of gut microbial communities by metabolic modeling.
Results: Simulation of these GEMs based on single species allows to quantify the production capabilities of gut bacteria towards synthesis of beneficial small molecules such as short chain fatty acids (SCFAs) and amino acids (AAs). Results demonstrate that variations in synthesis of small molecules are directly connected to changes in gut microbiota composition between healthy and malnourished children. Focusing on the effects of food interventions on gut microbiota and host metabolism, we found transient effects of standard Ready-To-Use-Food treatment to gut microbiome.
Conclusions: Results of this study suggested that the gut microbiota in Bangladeshi and Malawian children is less diverse than Swedish cohort. There is only a slight difference in production of SCFAs and AAs between healthy and malnourished Bangladeshi children. For Malawian children there seems to be no metabolic difference between healthy and malnourished children, which could point to an effect of vitamins and/or minerals. The metabolic diversity of both Malawian and Bangladeshi children is much lower than in Swedish children, which may point to a problem with lack of microbiota diversity connected to malnutrition.
#This work is sponsored by the Bill & Melinda Gates Foundation, Healthy birth, growth and development initiative.
References:
[1] Smith, M. I. et al. Gut Microbiomes of Malawian Twin Pairs Discordant for Kwashiorkor. Science (80-. ). 339, 548–554 (2013).
[2] Subramanian, S. et al. Persistent gut microbiota immaturity in malnourished Bangladeshi children. Nature 29–31 (2014). doi:10.1038/nature13421
[3] Bäckhed, F. et al. Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life. Cell Host Microbe 17, 690–703 (2015).
Reference: PAGE 25 () Abstr 5832 [www.page-meeting.org/?abstract=5832]
Poster: Methodology - New Modelling Approaches