Methods are provided for the rational design of stable communities of microbes for benefiting the health of a host organism, including human and/or animal health. The methods describe design of microbial consortia based on providing and/or complementing key functionalities lacking or underrepresented in the microbiome of an organism having a disorder or disease as compared to healthy subjects. The consortia are designed to possess metabolic interdependencies for improved engrafting, stability and performance of the consortium. Compositions that include the designed microbial consortia are provided for treatment of disorders/diseases involving chronic inflammation, infection, and the combination of chronic inflammation and infection including inflammatory bowel disease and related disorders. The compositions are also broadly applicable for the treatment of neurological, metabolic and oncology-related conditions.
