Project Type: review and perspective

A diagram with two panels, and a cartoon mouse in the middle. The cartoon mouse is eating broccoli, and a cartoon of the digestive tract is overlaid on the mouse's abdomen. Lines emanating from the broccoli point to the left panel, and show the compound glucoraphanin being converted into sulforaphane by the myrosinase enzyme. Lines emanating from the colon of the mouse point to the panel on the right, showing the same biochemical conversion by gut microbes.

Interplay of broccoli/broccoli sprout bioactives with gut microbiota in reducing inflammation in inflammatory bowel diseases

As part of her master’s of science thesis in 2022, 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.

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.
Figure 1. Primary Inflammatory Bowel Disease presentations, ulcerative colitis (UC) and Crohn’s disease (CD), compared to a healthy colon. UC is limited to the colon and is characterized by pseudopolyps and haustra loss (smoothing and shortening of the colon). CD can occur anywhere in the GI tract and is characterized by fissures, muscle thickening, and “cobblestoning”, which is the unique bubbling of the interior wall.

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 (work that has been funded by the Allen Foundation). 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 review, work that has been funded by the NIH).

A diagram with two panels, and a cartoon mouse in the middle. The cartoon mouse is eating broccoli, and a cartoon of the digestive tract is overlaid on the mouse's abdomen. Lines emanating from the broccoli point to the left panel, and show the compound glucoraphanin being converted into sulforaphane by the myrosinase enzyme. Lines emanating from the colon of the mouse point to the panel on the right, showing the same biochemical conversion by gut microbes.
Figure 2. (A) Glucoraphanin hydrolysis in the presence of plant myrosinase upon damage to the broccoli plant. Epithiospecifier protein preferentially converts glucoraphanin to sulforaphane-nitrile. (B) Glucoraphanin hydrolysis has been demonstrated by gut bacteria in the cecum and colon of mammals. Low pH environments favor conversion to sulforaphane-nitrile.

Interplay of Broccoli/Broccoli Sprout Bioactives with Gut Microbiota in Reducing Inflammation in Inflammatory Bowel Diseases.

Holman, J., Hurd, M., Moses, P.,  Mawe, G.,  Zhang, T., Ishaq, S.L., Li, Y. 2022. The Journal of Nutritional Biochemistry 113: 109238.

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 person’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.

Acknowledgements: The authors would like to thank Brigitte Lavoie (University of Vermont) and Grace Chen (University of Michigan), as well as undergraduate researchers Dorien Baudewyns (Husson University), Louisa Colucci (Husson University), and Joe Balkan (Tufts University), for their work on the laboratory research which forms the broader collaboration that led to the generation of this review. All authors have read and approved the final manuscript. This project was supported by the USDA National Institute of Food and Agriculture, Hatch Project Numbers ME0-22102 (Ishaq) and ME0-22303 (Li) through the Maine Agricultural & Forest Experiment Station, and USDA-NIFA-AFRI Foundational Program [Grant No. 2018-67017-27520]. It was also supported by NIH grant NOA R21AT011203 (Mawe).

Conflict of Interest: The authors declare no conflicts of interest.

Designing the Microbes and Social Equity Symposium, a Novel Interdisciplinary Virtual Research Conference Based on Achieving Group-Directed Outputs

This collaborative paper on the 2021 Microbes and Social Equity Symposium was invited by the Challenges journal’s editor-in-chief to submit a contribution about the group’s activities, and the together the session organizers, speakers, student assistants, and I wrote about our experiences putting this together. The journal is dedicated to published highly interdisciplinary research which looks things from multiple perspectives and which contributes to Planetary Health.

We learned that, much like microbes, audiences don’t always act the way you expect them to. Even better: we learned that by providing collaborative working time after listening to speaker sessions, which could be used to get our thoughts down on paper, we could capture the magic and inspiration of the conversations we had post-talks and revisit those later as research and outreach resources.

Ishaq, S.L., Wissel, E.F., Wolf, P.G., Grieneisen, L., Eggleston, E.M., Mhuireach, G., Friedman, M., Lichtenwalner, A., Otero Machuca, J.,  Weatherford Darling, K.,  Pearson, A., Wertheim, F.S., Johnson, A.J., Hodges, L., Young, S., Nielsen, C.C., Kozyrskyj, A.L.,  MacRae, J.D., McKenna Myers, E., Kozik, A.J., Tussing-Humphreys, L.M., Trujillo, M., Daniel, G.A., Kramer, M.R., Donovan, S.M., Arshad, M., Balkan, J., Hosler, S. 2022. Designing the Microbes and Social Equity Symposium, a novel interdisciplinary virtual research conference based on achieving group-directed outputs. Challenges, 13(2), 30.

Abstract: The Microbes and Social Equity working group was formed in 2020 to foster conversations on research, education, and policy related to how microorganisms connect to personal, societal, and environmental health, and to provide space and guidance for action. In 2021, we designed our first virtual Symposium to convene researchers already working in these areas for more guided discussions. The Symposium organizing team had never planned a research event of this scale or style, and this perspective piece details that process and our reflections. The goals were to 1) convene interdisciplinary audiences around topics involving microbiomes and health, 2) stimulate conversation around a selected list of paramount research topics, and 3) leverage the disciplinary and professional diversity of the group to create meaningful agendas and actionable items for attendees to continue to engage with after the meeting. Sixteen co-written documents were created during the Symposium which contained ideas and resources, or identified barriers and solutions to creating equity in ways which would promote beneficial microbial interactions. The most remarked-upon aspect was the working time in the breakout rooms built into the schedule. MSE members agreed that in future symposia, providing interactive workshops, training, or collaborative working time would provide useful content, a novel conference activity, and allow attendees to accomplish other work-oriented goals simultaneously.

Many questions remain unanswered about the role of microbial transmission in epizootic shell disease in American lobsters (Homarus americanus).

Lobsters are an iconic part of Maine culture, from cuisine to interior decorating to way of life. The Gulf of Maine boasts large lobster landings every year, but as the waters here continue to warm at a faster rate than other nearby coastal regions, there are concerns that this boon might eventually pass us by as lobsters migrate further north in search of colder waters. In addition to rising temperatures along the northeastern coast, we’ve seen an increase in epizootic shell disease (ESD) in the last few decades. ESD causes degradation and pitting of the lobster shell which can leave them susceptible to predation or to harsh weather conditions. There are bacteria living on the shell of healthy lobsters, and it’s not clear how they are involved in ESD in the wild because it is difficult to replicate this disease in an aquaculture facility.

In this perspective piece, we consider how shell microbes might be involved. Marine environments have a thriving microbial community which can change rapidly when currents, storms, filter feeders, or viruses which target microbes roll through. Some of these water or soil microbes end up on lobster shells, and water currents can also lift microbes off and move them elsewhere. The other authors and I wanted to highlight some of these possibilities and what we still don’t know about lobster microbes and health.

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Some slides from a previous presentation on lobster microbes.
A steamed lobster on a plate.

This perspective piece is part of a larger, collaborative project on lobster shell disease and warming ocean waters was begun by researchers at the Aquaculture Research Institute: Debbie Bouchard, Heather Hamlin, Jean MacRae, Scarlett Tudor, and later Sarah Turner as a grad student. I was invited to participate in the data analysis aspect two years ago.

At the time, Grace Lee was a rising senior at Bowdoin College, and accepted to my lab for the UMaine REU summer 2020 session, which was canceled. Instead, I hired Grace to perform DNA sequence analysis remotely, by independently learning data analysis following the teaching materials I had generated for my sequencing class.  I invited Joelle Kilchenmann to this piece after a series of conversations about microbes and social equity, because her graduate work in Joshua Stoll’s lab focuses on lobster fishing communities in Maine and understanding the challenges they face.

Ishaq, S.L., Turner, S.M., Tudor, M.S.,  MacRae, J.D., Hamlin, H., Kilchenmann, J., Lee1, G., Bouchard, D. 2022. Many questions remain unanswered about the role of microbial transmission in epizootic shell disease in American lobsters (Homarus americanus). Frontiers in Microbiology 13: 824950.

This was an invited contribution to a special collection: The Role of Dispersal and Transmission in Structuring Microbial Communities

Abstract: Despite decades of research on lobster species’ biology, ecology, and microbiology, there are still unresolved questions about the microbial communities which associate in or on lobsters under healthy or diseased states, microbial acquisition, as well as microbial transmission between lobsters and between lobsters and their environment. There is an untapped opportunity for metagenomics, metatranscriptomics, and metabolomics to be added to the existing wealth of knowledge to more precisely track disease transmission, etiology, and host-microbe dynamics. Moreover, we need to gain this knowledge of wild lobster microbiomes before climate change alters environmental and host-microbial communities more than it likely already has, throwing a socioeconomically critical industry into disarray. As with so many animal species, the effects of climate change often manifests as changes in movement, and in this perspective piece, we consider the movement of the American lobster (Homarus americanus), Atlantic ocean currents, and the microorganisms associated with either.

Related presentations

Ishaq*, S.L., Lee, G., MacRae, J., Hamlin, H., Bouchard, D. “The effect of simulated warming ocean temperatures on the bacterial communities on the shells of healthy and epizootic shell diseased American Lobster (Homarus americanus).” Ecological Society of America 2021. (virtual). Aug 2-6, 2021. (accepted talk)

Ishaq*, S.L., Lee, G., MacRae, J., Hamlin, H., Bouchard, D. The Effect Of Simulated Warming Ocean Temperatures On The Bacterial Communities On The Shells Of Healthy And Epizootic Shell Diseased American Lobster (Homarus americanus). ASM Microbe/ISME World Microbe Forum 2021 (virtual). June 20-24, 2021. (poster)

Framing the discussion of microorganisms as a facet of social equity

In just a four-week course in 2019 when I was working at the University of Oregon, I introduced 15 undergraduates from the UO Clark Honors College to microorganisms and the myriad ways in which we need them. More than that, we talked about how access to things, like nutritious foods (and especially fiber), pre- and postnatal health care, or greenspace and city parks, could influence the microbial exposures you would have over your lifetime. Inequalities in that access – such as only putting parks in wealthier neighborhoods – creates social inequity in resource distribution, but it also creates inequity in microbial exposure and the effect on your health.

By the end of the that four weeks, the students, several guest researchers, and myself condensed these discussions into a single paper (a mighty undertaking, indeed). Interest in this paper sparked the formation of the Microbes and Social Equity working group.

During the course, a number of guest lecturers were kind enough to lend us their expertise and their perspective:

Ishaq, S.L., Rapp, M., Byerly, R., McClellan, L.S., O’Boyle, M.R., Nykanen, A., Fuller, P.J., Aas, C., Stone, J.M., Killpatrick, S., Uptegrove, M.M., Vischer, A., Wolf, H., Smallman, F., Eymann, H., Narode, S., Stapleton, E., Cioffi, C.C., Tavalire, H..  2019.  Framing the discussion of microorganisms as a facet of social equity in human health. PLoS Biology 17(11): e3000536.

Abstract

What do “microbes” have to do with social equity? These microorganisms are integral to our health, that of our natural environment, and even the “health” of the environments we build. The loss, gain, and retention of microorganisms—their flow between humans and the environment—can greatly impact our health. It is well-known that inequalities in access to perinatal care, healthy foods, quality housing, and the natural environment can create and arise from social inequality. Here, we focus on the argument that access to beneficial microorganisms is a facet of public health, and health inequality may be compounded by inequitable microbial exposure.