Li and Ishaq labs receive NIH R15 award to study broccoli bioactives, gut microbes, and inflammation!

The Li and Ishaq labs at UMaine, along with collaborators from multiple institutions, have been awarded R15 funding from the National Institute Of Diabetes And Digestive And Kidney Diseases of the National Institutes of Health!

This award will complement other projects/awards led by our team, which has been investigating inflammatory bowel diseases, anti-inflammatories, gut microbes, and nutrition, separately for decades and collaboratively for over two years.

  • Dr. Yanyan Li, PhD (lead PI), Assistant Professor at the University of Maine with expertise in nutrition and food science, particularly dietary bioactives and colitis;
  • myself (co-PI), with expertise in host-associated microbiology, especially GI tract;
  • Dr. Grace Chen, MD, PhD (co-I), Associate Professor at the University of Michigan, expertise in mouse models for gut microbiome and colonic host immune responses;
  • Dr. Tao Zhang, PhD (consultant), Assistant professor at Binghamton University, with expertise in metabolism, kinetics, and bioanalysis of natural products;
  • Dr. Gary Mawe, PhD (consultant), Professor at the University of Vermont, with expertise in translational research on GI tract regulation, inflammation, and IBD;
  • Dr. Peter Moses, MD (consultant), Professor Emeritus at the University of Vermont College of Medicine and Senior Researcher at GSK, with expertise in IBD and functional gastrointestinal disorders.

R15 Research Enhancement Awards are designated for projects which involve a large number of student researchers. Between the Li and Ishaq labs, there are three current graduate students, and two former undergrads who have contributed to this research, and we anticipate bringing in 1-2 additional graduate students and almost a dozen undergrads in the next year! That will include undergrads in Honors, Top Scholars, and Capstone programs at UMaine. We’ve also been assisted by the work of students, postdocs, technicians, and investigators through our collaborators, and we are ecstatic about the opportunity to continue to grow our team across institutions. And, this project will generate research that will feed back into education at UMaine through the courses that we teach, such as my microbiomes and DNA sequence analysis courses.

“Harnessing gut microbiota to reduce inflammation using broccoli-sprout diets.”

Project Summary:

Inflammatory bowel disease (IBD) is a poorly understood gastrointestinal (GI) condition characterized by inflammation. The prevailing theory is that combined genetic and environmental factors disrupt the host immune system’s interaction with gut microbiota. Our central hypothesis is that consumption of specific broccoli sprout preparations elicits changes in the gut microbiota that not only improve the production of anti-inflammatory bioactives, but also promote intestinal homeostasis. Our labs have shown there is an anatomical pattern along the GI tract where broccoli sprout-derived bioactive levels are high which correspond to diet-induced changes in gut microbial communities. We showed that gut microbiota contribute to the transformation of inactive precursors to bioactives, and that specific broccoli sprout preparations alter their capacity for biotransformation, and the susceptibility of mice to colitis. However, a significant knowledge gap remains regarding the mechanisms by which dietary bioactives modify disease risk and the role of gut microbiota. Our immediate goal is to identify the mechanisms by which broccoli sprout diets affect susceptibility to IBD in mice. Our long-term goal is to develop a dietary preparation of
broccoli sprouts which has therapeutic effects against IBD in humans. Our innovative approach uses different preparations of broccoli sprouts to help differentiate gut microbiota versus plant-derived
enzymatic activities. We employ a combination of “omics” approaches to spatially-map the microbial community and metabolite profile changes along the GI tract, to better assess changes induced by broccoli sprout diets. We complement “omics” approaches with culturing, and validate our study design using two complementary models for strategic research.

A cartoon of three gastrointestinal tracts showing the locations of inflammation in ulcerative colitis, crohn's disease, or healthy tissue. At the bottom are cross-sections showing thickening of the intestinal wall in patients with Crohn's, and ulcers in patients with colitis.
Created by Johanna Holman.

Aim 1 tests the hypothesis of an anatomical pattern where the GI tract microbiota transform broccoli compounds into bioactives, and helps us determine whether this microbial biotransformation is sensitive to dose of broccoli compounds. We will use our established DSS-mouse-model of ulcerative colitis to investigate the effects of different broccoli sprout preparations and concentrations on the microbiota along the GI tract; on the resulting concentration of bioactives in gut tissues; and on the development of colitis in mice.

A cartoon schematic of the experimental design of the project. Four mice are at the top, two have "DSS" written above them, one of which is also holding a broccoli sprout. One of the mice without DSS written on it is holding a broccoli sprout. Below the mice is a cartoon of the digestive tract with arrows emanating from it to indicate samples of microbes will be taken from different locations. The microbe images have arrows pointing to culturing equipment, and also to a biochemical pathway showing the compound glucoraphanin being converted to sulforaphane.
Created by Sue Ishaq, made with Biorender

Aim 2 tests the benefits of using an immunosuppressed mouse model in the dietary prevention study to provide a stronger translational strategy for the use of broccoli sprouts for IBD prevention. When exposed to a specific bacterial pathogen, the immunosuppressed mice develop chronic enterocolitis resembling Crohn’s disease. This diet-based approach provides critical information for developing accessible and equitable strategies for improving health of IBD patients.

A cartoon schematic of the experimental design of the project. Two mice are at the top, with the label "IL-10" crossed out above them. One mouse is also holding a broccoli sprout.  Below the mice is a cartoon of the digestive tract with arrows emanating from it to indicate samples of microbes and tissue will be taken from different locations. The words weight and plasma indicate those will also be collected. The plasma and tissue samples will be used for mass-spectroscopy and histology, and the microbes will be used for DNA sequencing.
Created by Sue Ishaq, made with Biorender

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