Defining stable microbial communities through functional interrogation of microbiomes

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The gastrointestinal tract (GIT) is home to a complex, yet stable, community of microbes conferring numerous benefits to their host. Over the past 80 years, microbial communities in the GITs of livestock have been augmented through dietary supplementation of sub-therapeutic doses of antibiotics (antibiotic growth promotants; AGPs), enhancing production efficiency and reducing enteric infections. However, due to concerns over the rise of anti-microbial resistance (AMR), AGPs are being phased out; alternatives are urgently required. With a need to engraft and persist in the GIT, allied to the success of fecal microbiome transplants, attention has shifted from the use of single strain probiotics, to synthetic microbial communities. In this five-year research program, we propose to develop effective genomic and computational pipelines to identify stable microbial communities that can be used to seed the developing GIT of poultry and help establish a healthy and productive microbiome. Three aims are proposed: AIM1. Develop innovative computational tools for accurately inferring taxonomic and functional compositions of microbiomes. Metatranscriptomics datasets have the power to yield mechanistic insights into microbiome function. To fully exploit their potential, we will develop next generation tools, based on ensemble methods, in which functional and taxonomic annotations are reciprocally bootstrapped to deliver accurate classifications. AIM2. Construct systems-based models to reveal functional dependencies within microbiomes. To better understand microbiome functionality, using annotations derived from Aim1, we will generate predictive models of microbial community metabolism. Applied in the context of poultry, these models will allow us to rapidly predict the functional impact of altering community composition, together with any consequence in nutrient acquisition by the host. AIM3. Design novel community probiotics to improve poultry health. Cliques of stably associating microbes, identified through community meta-analyses, will be investigated through predictive metabolic models established in Aim2, to identify synthetic microbial communities that promote poultry gut health. The efficacy of these communities will be validated through established strategic partnerships. Supporting this program of research is a talented team of computational biologists, including undergraduate and graduate students, together with postdoctoral fellows. Developing complementary skills in high-performance computing, microbiome analysis and systems biology, trainees in this program will receive a diverse training experience, preparing them for a multitude of career opportunities in academia, as well as industry. Together with established collaborations with experts in poultry health, this program will deliver fundamental insights into the molecular interactions that drive microbiome dynamics and establish new synthetic communities that promote poultry health.