Every year, The University of Maine releases a summary report of the research efforts of its faculty, staff, and students. I was pleased to discover that the work that Yanyan Li and I have been doing on broccoli sprouts and gut microbes was featured in the report! A screenshot of the story is below, but you can read the story and the entire 2022 UMaine research report here.
The Ishaq Lab is pleased to welcome Marissa Kinney as a Master’s of Science student in Microbiology, beginning in January 2023! She’ll be joining ‘Team Broccoli‘ to investigate the 806 bacteria we isolated from the digestive tracts of mice eating a broccoli sprout diet, in a previous experiment on broccoli sprouts, microbes, and resolving colitis.
Marissa is a recent graduate of the UMaine Microbiology bachelor’s program, where she was part of an interdisciplinary research group and was the first author on a scientific publication this year: Suppression of Methicillin-Resistant Staphylococcus aureus and Reduction of Other Bacteria by Black Soldier Fly Larvae Reared on Potato Substrate.
Master of Science student, Microbiology and Animal and Veterinary Sciences
Blurb: Marissa is a Masters student who loves learning and bench microbiology. She completed her undergraduate at the University of Maine in 2021, earning a BS in Microbiology and a BS in Cellular/Molecular Biology. She devoted a large portion of her time in undergrad to research in the laboratories of Dr. Julie Gosse and Dr. Edward Bernard. Since graduating, she worked in the field of public health at UMaine’s Margaret Chase Smith Policy Center, collecting and processing data about violent and drug-related deaths in Maine. While her role at the Center was one she loved dearly, she feels a big pull towards laboratory work and academic research. She recently joined the Ishaq lab and is excited by the new opportunities this position brings.
A massive literature review led by Johanna Holman, and featuring our collaborative team of broccoli sprout and microbes researchers, was accepted for publication!
As part of her master’s of science thesis, Johanna Holman reviewed hundreds of journal articles on anti-inflammatory, health-promoting dietary compounds in broccoli and other vegetables or fruits, and how microbes in the digestive tract can transform inactive precursors from foods into those beneficial compounds. This is part of a broader research collaboration on how glucoraphanin in broccoli sprouts can be made into sulforaphane, which acts as an anti-inflammatory in humans. Humans are unable to convert glucoraphanin to sulforaphane, and a small amount of this occurs naturally thanks to enzymes in the broccoli sprouts. But, certain gut microbes can make the conversion and this has helped resolve colitis and other symptoms in mice in laboratory trials (manuscripts in preparation).
If you aren’t familiar with broccoli sprouts, a lovely review on their history, current food culture, and safe production was just published by some of our colleagues: Sprout microbial safety: A reappraisal after a quarter-century.
Holman, J., Hurd, M., Moses, P., Mawe, G., Zhang, T., Ishaq, S.L., Li, Y. 2022. Interplay of Broccoli/Broccoli Sprout Bioactives with Gut Microbiota in Reducing Inflammation in Inflammatory Bowel Diseases. Journal of Nutritional Biochemistry, in press.
Abstract
Inflammatory Bowel Diseases (IBD) are chronic, reoccurring, and debilitating conditions characterized by inflammation in the gastrointestinal tract, some of which can lead to more systemic complications and can include autoimmune dysfunction, a change in the taxonomic and functional structure of microbial communities in the gut, and complicated burdens in a person’s daily life. Like many diseases based in chronic inflammation, research on IBD has pointed towards a multifactorial origin involving factors of the host’s lifestyle, immune system, associated microbial communities, and environmental conditions. Treatment currently exists only as palliative care, and seeks to disrupt the feedback loop of symptoms by reducing inflammation and allowing as much of a return to homeostasis as possible. Various anti-inflammatory options have been explored, and this review focuses on the use of diet as an alternative means of improving gut health. Specifically, we highlight the connection between the role of sulforaphane from cruciferous vegetables in regulating inflammation and in modifying microbial communities, and to break down the role they play in IBD.
Yanyan Li and I sat down yesterday with Carly D’Eon, a reporter with News Center Maine, to talk about our ongoing research into broccoli sprouts, gut microbes, and Inflammatory Bowel Disease!
UMaine News recently highlighted some of the collaborative work that Yanyan Li and I have been doing at UMaine! You can read more about our projects here, here, and here.
This work features researchers from other universities, including:
•Dr. Tao Zhang, PI, SUNY Binghamton
•Dr. Grace Chen, PI, MSU
•Dr. Gary Mawe, PI, UVM
•Molly Hurd, PhD student, UVM
•Bridgette Lavoie, RA, UVM
•Dr. Peter Moses, PI, Finch Therapeutics
•Johanna Holman, MS student, Umaine
•Lola Holcomb, PhD student, UMaine
•Louisa Colucci, undergrad at the time, Husson
Joe Balkan, Undergrad, Tufts
•Dr. Emma Perry, UMaine Microscopy Facility
In addition to the two new funding sources listed in the article, we have been supported by:
•Maine Agricultural and Forestry Experimental Station
•ME0-22102 (Ishaq) and ME0-22303 (Li)
•USDA-NIFA-AFRI Foundational Program [Grant No. 2018-67017-27520]
•UMaine Institute of Medicine
•Maine Center for Genetics in the Environment
• UMaine GSBSE
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.
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.
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.
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.
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.
The Allen Foundation awarded Dr. Yanyan Li, Assistant Professor of Food Science and Human Nutrition, and myself funding for a pilot project in people on broccoli sprouts, the gut microbiome, anti inflammatory compounds, and health! Dr. Li and I, as well as a team of other researchers, have been collaborating over the last three years to understand how certain gut microbes create an anti-inflammatory compound using a compound in broccoli sprouts, and how we can use this action to calm colitis. Over the next 18 months, we will be recruiting a small group of people to participate in a diet trial. This will form the first part of the PhD work for Johanna Holman, who recently defended her master’s of science at UMaine.
Project Summary:
There is increasing evidence that diet and the gut microbiota have significant impact on human health and thus impact susceptibility to disease such as inflammatory bowel disease. Indeed, a Westernized diet has been associated with higher risk for developing inflammatory bowel disease, primarily as ulcerative colitis and Crohn’s disease, while a diet rich in fruits and vegetables tends to reduce risk. Our preliminary data suggests that a specific whole-food preparation of broccoli sprouts protects against the development of colitis in a chemically-induced mouse model as well as in a transgenic mouse model of Crohn’s disease. Furthermore, the gut microbiome contributes to the generation of the active anti-inflammatory component, sulforaphane, from broccoli sprouts, and the microbiome, in turn, is altered by exposure to broccoli sprouts or its metabolites. Thus, our long-term goal is to understand the interactions between anti-inflammatory bioactives of broccoli sprouts and the gut microbiome. The current proposal aims to increase our understanding of the nutrigenomics of the human microbiome and a broccoli sprout diet in healthy subjects. Our goal is to determine the feasibility of incorporating a specific broccoli sprout preparation into whole-food diets to increase levels of anti-inflammatory bioactives from broccoli sprouts in healthy humans. These directly address the foundation’s priority of “bringing the promise of nutrigenomics or nutritional genomics to realization”. Results from this study will help determine the feasibility and potential efficacy of a whole food approach in promoting intestinal homeostasis and mitigating risk of developing inflammatory bowel disease.
Johanna Holman passed her Master’s of Science these defense (we knew she would succeed)!! Johanna has worked incredibly hard over the last two years to broaden her research skills and conduct several experiments, and her defense presentation was a wonderful way to see that progression all at once. She has also earned the designation of “first Ishaq Lab grad student to defend”. The defense was attended by her thesis committee, students in the Ishaq lab, collaborators on this project, and friends and family (who brought her a flower and broccoli bouquet that can be seen in the picture below). She will officially pass after a few revisions to her thesis and a formal acceptance by the committee members, which is standard for graduate defenses.
Johanna has been accepted to the Nutrition PhD program at UMaine, and will continue working with Dr. Li and I, as well as the full research team. Based on those preliminary results, Johanna’s doctoral work will focus on developing that new mouse model, synthesizing information from both models, and using those results to develop diet intervention trials in human patients. After her PhD, Johanna intends to conduct research at an institution here in Maine, and to continue her work connecting the biochemistry of nutrition with gut microbiology and human health.
Mice have arrived for a collaborative project on diet, gut microbes, and health in conjunction with researchers at Husson University! This is the first mouse project for the Ishaq Lab, and also my first hands-on mouse project (in my previous publications with mice, I received datasets but the mouse work was performed solely by my collaborators).
This is one of my first new collaborations at the University of Maine, which began in September 2019 as I was just finding my way around campus. An established researcher at Husson University, Dr. Yanyan Li, reached out to welcome me and talk about overlap between our work. Yanyan, her husband Dr. Tao Zhang, also a researcher at Husson University, and collaborator Dr. Grace Chen at Michigan State University, had been working on beneficial compounds found in broccoli using mice as an experimental model for Inflammatory Bowel Disease (IBD). Over the past year, in consultation with IBD experts Drs. Gary Mawe and Peter Moses (who I worked with previously while at UVM!), we have written several proposals for funding to expand the project.
Johanna Holman worked for several years with Yanyan and Tao, as an undergraduate researcher and then as a research assistant. She joined the Ishaq Lab this fall to continue her work as a graduate student and add gut microbiology to her skill repertoire. This experiment will form the base of her graduate thesis, and Johanna is taking a lead role in managing the project as well as several undergraduate researchers, including Dorien Baudewyns, assisting with the mice and lab work. As an early career researcher, and new to mice, I’m extremely lucky to be able to learn from an experienced team of researchers!
