Lab Research

The microbial cells that colonize the human body outnumber host cells by an order of magnitude. Recent advances in high throughput sequencing technologies have unveiled great variability in the microbiome, and shifts in the composition of microbial communities have been associated with multiple health conditions, such as diabetes, inflammatory bowel disease, obesity, and cancer. Although the human microbiome is influenced by environmental factors, microbial composition is also shaped by host genes and genetic variation. In turn, microbes can affect the host by regulating gene expression interacting epithelial cells.

We study host genomic factors that control and interact with the microbiome. We utilize high-throughput genomics technologies and employ computational, statistical, network-theory, data mining, and population genetic analytical approaches, with the goal of understanding how we interact with our microbial communities, how host-microbe interactions affect human disease, and how the symbiosis between us and our microbiome evolved. We aim to answer the following questions:

1. What are the molecular and genetic mechanisms controlling host-microbe interactions?
We develop and apply machine learning methods to integrate microbiome and host genomic data to characterize associations between host genes and microbial taxa, and understand how these associations change in health and disease. Recent publications in this area:

Identification of shared and disease-specific host gene–microbiome associations across human diseases using multi-omic integration
Priya et al., Nature Microbiology, 2022
Multi-omics analyses show disease, diet, and transcriptome interactions with the virome
Mihindukulasuriya et al., Gastroenterology, 2021
Longitudinal multi-omics reveals subset-specific mechanisms underlying irritable bowel syndrome
Mars et al., Cell, 2020

2. How does host genetic variation impact the microbiome?
What is the heritability of the microbiome, how is it affected by different environmental and host factors, how does it change over time? Recent publications in this area:

Gut microbiome heritability is nearly universal but environmentally contingent
Grieneisen et al., Science, 2021
Host genetic variation impacts microbiome composition across human body sites
Blekhman et al., Genome Biology, 2015


Human genetics shape the gut microbiome
Goodrich et al., Cell, 2014

3. What is the effect of variation in the microbiome on host gene regulation?
What are the differences in the microbiome between individuals, human populations, and hominid species, and how do these affect host physiology through regulation of gene expression in interacting host cells? Recent publications in this area:

Interspecies variation in hominid gut microbiota controls host gene regulation
Muehlbauer et al., Cell Reports, 2021
Gut microbiota diversity across ethnicities in the United States
Brooks et al., PLOS Biology, 2018
Gut microbiome of coexisting BaAka pygmies and Bantu reflects gradients of traditional subsistence patterns
Gomez et al., Cell Reports, 2016

4. How do host-microbiome interactions control susceptibility to colorectal cancer?
What are the unique roles of tumor genetics and microbial communities, and how do they interact to affect cancer susceptibility, progression, and treatment? Recent publications in this area:

Interactions between the gut microbiome and host gene regulation in cystic fibrosis
Dayama et al., Genome Medicine, 2020
Colorectal cancer mutational profiles correlate with defined microbial communities in the tumor microenvironment
Burns et al., PLOS Genetics, 2018
Interaction between host microRNAs and the gut microbiota in colorectal cancer
Yuan et al., mSystems, 2018

5. Meta-research
We mine and analyze large-scale datasets to quantify how research (in microbiome, genomics, and biology) is performed, communicated, and shared, quantify issues and biases, and highlight potential solutions. Recent publications in this area:

Public human microbiome data are dominated by highly developed countries
Abdill et al., PLOS Biology, 2022
International authorship and collaboration across bioRxiv preprints
Abdill et al., eLife, 2020
Challenges and recommendations to improve the installability and archival stability of omics computational tools
Mangul et al., PLOS Biology, 2019
Tracking the popularity and outcomes of all bioRxiv preprints
Abdill & Blekhman, eLife, 2019

Collaborators

Funding

We are thankful to the various funding agencies and institutions that have supported our research throughout the years, including the National Institutes of Health, National Science Foundation, Alfred P. Sloan Foundation, American Cancer Society, University of Minnesota, and University of Chicago.

Our lab is currently funded through the following grant awards: