You know that friend who never gets sick? We do too, and we want to learn their secret. Our project is designed to create a powerful probiotic supplement by studying these ‘Resisters’ who have natural, above-average ability to fight off infections like the common cold or flu. We believe their superpower lies in their unique gut microbiome. We hypothesize that Resisters have distinctive gut microbiomes profiles containing bacterial strains that can enhance immune resilience.
Your gut is home to trillions of bacteria, and we’re just learning its language. These microscopic allies—your microbiome—have a staggering impact on your immune, metabolic, and even mental health. In recent years, studies have directly linked gut bacteria to the severity of COVID-19 infections, the development of allergies, and even how well you respond to vaccines. While existing probiotics with bacteria like Lactiplantibacillus plantarum and Lactobacillus plantarum HEAL 9 offer a mild, but significant protection against colds, we’re not aiming for “mild.” We are expanding on this research to find the specific bacterial dream team that can dramatically upgrade your immune defenses against systemic infections. We hypothesize that by profiling the Resisters’ microbiome, we can specifically identify bacteria which aid in host immune defense via bacterial derived metabolites and their interactions with the host’s immune system.
The COVID-19 pandemic taught us a hard lesson: we need better, faster defenses. Imagine a general prophylactic that strengthens your immune system against future pandemics, buying the world precious time while vaccines are developed. By decoding the blood and gut microbiome signatures of people with naturally heightened immunity, we can pinpoint the exact microbes that grant this resistance. This technology can protect the public from common and costly infections, improving quality of life for millions and easing the massive financial burden on our healthcare system. The flu alone costs the US an estimated $90 billion annually. It’s time for a smarter defense. By profiling the Resister microbiome, we hope to create a general prophylactic probiotic to aid the general public’s ability to fight off infections.
Our mission will follow a three-step process. First, we will recruit the elite by identifying and enrolling twelve “Resisters” to donate the blood and stool samples that hold their immunological secrets.
Second, we will decode the blueprint by fingerprinting their stool with next-generation sequencing to map their gut bacteria, while using cytokine multiplexing and untargeted metabolomics on their blood plasma to reveal the host–microbiome interactions that give them an edge.
Finally, we will build the shield by testing the identified bacteria—alone and in powerful consortia—in vitro using human-derived macrophage cell lines to assess their ability to help immune cells fend off infections and to build our prototype probiotic.
Nanopore long-read sequencing will allow us to identify the bacteria of interest within the Resister population and create Metagenome-Assembled Genomes (MAGs) for bacteria of interest.
Using plasma collected from Resisters, we can look at the cytokine distribution and metabolites present in blood to determine which signatures confer the Resister phenotype and what metabolites are microbial in origin.
Once we have identified the bacteria of interest, we must isolate them from stool using traditional culturomics methods to allow for further testing and DNA sequencing.
Finally, as a proof of concept that the Resister derived bacteria are able to improve the body’s ability to fight infections, we will perform a THP-1 macrophage infection model to determine the bacteria’s ability to aid in infection clearance.
This project brings together academic expertise and industry innovation through a collaboration between Northeastern University researchers and the biotechnology company Holobiome.
Daniel Norment, the PhD student investigator within the Lewis lab, has obtained his Master’s degree in biochemistry and molecular biology from the University of Massachusetts Amherst and has two years of industry experience working for Holobiome. Daniel specializes in working with human gut bacteria and translating DNA sequencing data into actionable insights.
Dr. Kim Lewis is a university distinguished professor and director of the Antimicrobial Discovery Center at Northeastern University in Boston Massachusetts. Dr. Lewis has authored over 100 papers, cofounded multiple biotechnology companies, and is an inventor on several patents. He has contributed to the development of general methods to grow previously uncultured bacteria, investigated drug-tolerant persister cells, and discovered several novel antibiotics. The Lewis lab has published high impact human microbiome papers in prestigious journals such as Nature Microbiology.
Dr. Strandwitz is a microbiome scientist turned entrepreneur. He was supported by one of the first grants in the Human Microbiome Project, and received his PhD in Biology in 2016 at Northeastern University in Dr. Kim Lewis’ laboratory. His graduate work was focused on cultivating the “uncultured” members of the human microbiome, resulting in publications in top journals like Nature Microbiology and Microbiome. He is now CEO at Holobiome, a platform biotech company that’s mapping how our microbes impact our biology and developing solutions from that knowledge in the form of drugs and consumer products. He’s brought in over $20M in capital to Holobiome, through non-dilutive grants, corporate partnerships, and venture capital. He’s also a Termeer Fellow, a mentorship network started by the founding CEO of Genzyme, Henri Termeer.
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