Location: Dairy and Functional Foods Research
Project Number: 8072-41000-108-014-N
Project Type: Non-Funded Cooperative Agreement
Start Date: Dec 1, 2023
End Date: Nov 30, 2026
Objective:
The proposed collaborative research project consists of 3 objectives.
Objective #1. To examine the effect the long-term exposure of nisin on the gut microbiota. Nisin is used for food preservation and is considered as a safe bacteriocin, but recent research indicated it could potentially impact the gut microbiota composition and function. This proposal aims to investigate the impact of nisin on the human gut microbiota using a simulator of the human intestinal microbial ecosystem.
Objective #2. Characterize the human gut microbiota and establish a standard ex vivo human intestinal microbial ecosystem, using all the existing human gut metagenomic data. It remains unclear whether there is a cohort of microbes that can represent different groups of humans, such as characteristic microbiota specific to certain age groups and certain ethnic groups. To address this open question, this project will mine the large set of metagenomic data for human gut microbiome. Various clustering algorithms will be applied to obtain characteristic microbial representations specific to different human phenotype groups.
Objective #3. Elucidating the fate and effect of selected antimicrobial peptides in and on the human digestive system. This project will examine both the fate of in-house designed and manufactured antimicrobial peptides once they are in the digestive system, and the effect of them on the gut microbiota. Metagenomic sequencing data will be collected and analyzed to characterize the dynamics of the microbiome and pathogen and antibiotic resistance changes.
Approach:
For Objective #1. V.T. scientists will develop computational workflows that process and analyze the metagenomic data and perform statistical tests to compare different parts of the digestive systems and analyze longitudinal microbiome data to identify patterns and anomalies. The USDA scientists in Wyndmoor, PA, will conduct the experiments with different doses of nisin in different parts of the simulated human digestive systems, also long-term exposure of different doses, and generate metagenomic sequencing data. Both groups will collaborate on running the workflows and analyzing the data and take part in discussion and interpretation of the results and write manuscripts together. Both will share first authorship and corresponding authorships as the work will be the result of close collaboration.
For Objective #2. The V.T. scientists will develop computational pipelines processing the large-scale metagenomic data, apply advanced supervised and unsupervised machine learning algorithms to identify feature microbiota that distinguish different groups of humans.
The USDA scientists in Wyndmoor, PA, will help curate the data from NCBI, identify the groups of humans of interest, formulate questions that can be addressed computationally. Both groups will work on the datasets in various ways to extract the microbial footprint that distinguishes different phenotypic groups of humans. Both will work on the manuscript and share the publication authorships based on the respective contributions.
For Objective #3. The V.T. scientists will develop new deep learning models that predict novel antimicrobial peptides from existing metagenomic sequencing data, as well as from generated artificial antimicrobial peptides. Will design an effective scoring system to rank the capability of the antimicrobial peptides in killing microbes.The USDA scientists in Wyndmoor, PA, will synthesize the selected antimicrobial peptides, feed them into the simulated human digestive systems, collect samples, and generate metagenomic sequencing data as well as metabolic data. Both groups will perform the data analyses and interpret the results together.
