Tag: collaboration

Blending art, science, and cheese in Venice at an Interdisciplinary workshop

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We’ve all felt the thrill of synchronicity when meeting someone for the first time and realizing how we have much in common, but when this occurs for a dozen people simultaneously, who go on to share ideas and excitement for 13 hours straight, it’s magic. Thus, Professor of Anthropology, Roberta Raffeta’, created magic when she invited a group of microbiome and health science researchers together for the “Integrating Qualitative and Quantitative Data in Microbiome Research and Postgenomics: Toward an Interdisciplinary Dialogue” workshop at the Università Ca’ Foscari Venezia. Roberta works with many disciplines, including microbiome, computational, health, and social sciences, and her work often focuses on how research is designed, implemented, and interpreted. Her work across disciplines gives a larger view on how different disciplines approach similar research, as well as provides her with a rich network of colleagues.

The workshop was in the spirit of a project that Roberta, Prof. Nicola Segata, Prof. Elena Bougleux, and others investigating the sharing of microbes at Antarctic stations based on social interactions and shared spaces. That project is a clear example of how social systems can determine who you interact with, where, and how, and thus which microbes might get shared between you or between everyone at the base. While those data were still being processed and not shared, we did get to hear a bit about the journey to Antarctica from Elena.

After introducing the project, workshop, and ourselves, we began with a presentation by Professor Federico Russo. Her talk focused on how health is quantified, and how that alters the way we design and perform health research. Health is a complex concept that has biological, chemical, physical, and social aspects which can be measured and metric-ified. For example, there are bio-logical versus bio-social metrics of health (social effects of disease, feelings about health and outlook), and everything in between which can be measured to assess the state of health or disease. In addition, health research uses the term “social determinants”, which is similar to what biologists, microbiologists, or ecologists mean when using the term “environmental factors”, but these often refer to the same thing. These factors are the collection of host, social/community, environmental, and geological features which affect who you are and what you encounter in your life. Some of them seem very specific, like age, but the expression of age can be modified by staying active, eating well, managing stress, and avoiding pollution, so on its own, knowing someone’s age might not be useful information.  Thus, to study health, we use both markers, like age, to tell us potential outcomes or indicators of one’s health state, and social determinants, like lifestyle features, to tell us possible causes or mitigating factors of health.

Yet, one cannot slice the concept of health into a thousand measurable factors and then expect to re-assemble them back into the concept it was – because what makes us feel well or healthy is not necessarily having or knowing that our biological metrics are good, it’s feeling well even if our biological markers are out “normal” parameters or when, on paper, we are sick.  This brings up a concept that I had discussions about within this workshop group, with the faculty at Ghent, and with researchers through MSE and MiSt: that your social factors and the support network around you strongly influence whether you feel well or unwell, regardless of what your biological markers would suggest.

There is also a focus in healthcare on regaining health when someone is sick, with social or institutional support system for that (rehabilitation clinics, etc.), but there is not always an institutional focus on understanding how people stay healthy, in part because this is seen as a personal choice and not a result of adequate access to public resources (fresh food, water, air, shelter, education, safety), or as a function of useful public health policies which make is easy for people to take care of themselves. Simple features like sidewalks, bike paths, local grocery stores, free public restrooms, shade and places to sit, are all features that allow people to stay active, get around, stay healthy, and use their public spaces.

My research talk was next, and I focused on the steamed broccoli sprout intervention trial I completed a few years ago with Yanyan Li. That was a pilot study, which recruited 20 people to steam and eat broccoli sprouts every day for a month, to measure any changes in the gut microbiome, the metabolites it was producing, and whether gut bacteria would convert the inactive glucoraphanin in sprouts into the anti-inflammatory compound sulforaphane. Rather than focus on the microbiological, metabolomic, or diet survey results, I presented everything which went unexpectedly in the study, and what people told us about the challenges to consuming daily sprouts. This, in fact, was the real goal of the study, to understand which aspects of the diet would be challenging, or rewarding, and to try and make things as easy as possible. My observations on the diet study sparked excellent discussion, which gave me plenty of ideas on framing the scientific manuscript and what we learned from our participant’s data, as well as a perspective piece on the design and implementation of the study and what we learned from our participants’ feedback (not their data).

Another study observation which was also a reoccurring workshop discussion was the need for health studies that start with people’s perspectives and patient’s identification of problems, which then work backwards to understand how the microbiome is involved. This style of research is case-study and health engineering research to test applied research questions, and is needed in addition to the large-scale, double-blind experiments to test basic research questions. We talked at length about how most large-scale diet surveys are inadequate, no matter how detailed they are, because they become so vague as to be useless when they are generalized to ask about all possible food item diets. Most diet surveys that are meant to be broad ask for too much detail about things which are considered superfluous for individual research projects, and too little detail on critical info. For example, most diet surveys that gather diet history (eating habits over the last 6 – 12 months) are underpowered to assess fermentation products, don’t ask how  people cook and make decisions about diet, and are quantified to assess compliance to an idealized and single idea of a healthy diet, even if it doesn’t work for every person (ex. dairy is good on many diet surveys but there is no place to select that you don’t consume dairy because you are allergic to it).

This discussion carried across lunch, during which we diverged into many animated conversations only to bring it back to quality of information in the presentation after lunch, by Professor Lisa Lehner, a health researcher who presented reflections on three research projects, in which the availability and completeness of data about patients was lacking, and this stymied researchers’ attempts to understand public health for three disease models, such as how these diseases are transmitted, how people access health care, and how migration, homelessness, or simply traveling often can impact access to care. For example, in trying to study human papilloma virus cases, her research found that country of sampling was included in patient records but not country of infection. Similarly,  the idea of “where do you live”, “where are you from”, or “where have you been recently where you might have contracted this infection” are very different questions with different contexts to the answers, not all of which will provide useful information for this specific study depending on which the patient was asked and what their history was.

Information sharing is both the key and the challenge, and we discussed how often the information to resolve public health crises exists, but it’s not all in one place, it’s missing information, it doesn’t contain the right context, institutions don’t want to share, some information is private or access is limited even to medical providers, some information is not retained, and even when we get much of this in one place the amount of detail is overwhelming to the point where researchers need to spend years trying to figure out how to make it useful – what’s important to know? What is a ‘red herring’? — before it even gets to be used for infection tracking, treatment, and prevention. Her research also highlighted inequities in healthcare, and that sometimes information that would help us understand infection data can’t be made public, because you might reveal information about sensitive populations that can be used for discrimination. For example, people without health insurance might be migrants that are no longer on active visas, and quantifying how many people can make them a political target.

The discussion after the talk was so engaging, and blended into the focus of another speaker, so we informally heard from Professor Donato Giovannelli, who was not able to present his talk (yet!) because the workshop was running later than expected (we all had so much to talk about!) and he had to catch a train. Donato is a geomicrobiologist examining microbes in extreme environments to understand how they survive and function. He has a particular focus on the microbial fixing of gaseous hydrogen which produces water, and how biological sinks for freshwater (like us walking, talking, water bottles), actually allow for the preservation of large quantities of water on Earth. Donato’s short version of his talk was focused on the scale of standardization in research. He argued that what works in the lab or the field changes based on the needs and circumstances of each project, so you need to thoroughly describe what you did but that doesn’t mean every lab uses, or has to use, the exact same protocols, kits, or methods every time. In fact, even if it were possible to replicate circumstances exactly, trying to do everything identically will just make all studies biased in the same ways. There is no way to replicate some experiments, especially with humans, because no human is ever replicable, even to ourselves.

Highlighting the importance of methods and process in research brought up another challenge in research: it is important to include vocabulary to describe what you mean, in addition to what you did, but Methods sections are often compressed by scientific journal word limits, and all the nuance and context or the problem-solving portion, gets cut for space and is over compressed to the point of being useless. Donato argued, as many scientists do, that the explanation of the methods should be the majority of the paper, and many labs do publish the long form of the methods as a co-published paper, or as a protocol paper that gets cited in the whole scientific experiment paper. Our workshop heartily agreed. Science is a process, as scientists we are creating this process and this is our most valuable contribution, more so, even, than the results.

Sometimes the drive for standardization also leaves out people who contributed to the study in a way, but their contribution is considered “not science”. For example, technicians, field personnel, or anyone who helped you access or collect samples but did not work on the samples or contribute “conceptual framing or interpretation” don’t count as authors under most journal guidelines, even if you could not have done the project without them. Similarly, if you designed your project based on feedback and direction from the public or specific audiences, this is somehow not considered “conceptualization” or experimental design (???!!!). It is always up to the author team to decide who is and isn’t an author, but without more flexible guidelines on authorship, it can be easy to remove someone’s contribution to a publication.

This type of value judgement in science segued us to our last presentation of the day, on how the terms/definitions we use, the factors we choose to study, the things we prioritize in our research, all reflect values we have placed on some things over other. It can also, unintentionally and intentionally, place inherent value on having certain study results or outcomes. And when the study is about people, placing value judgements on biological, microbiological, or social factors can create a hierarchy – you can see where I am going with this – in which certain people are implied to have superior metrics. This is something a research team and I published on in microbiome research, and has been the focus of a multi-year project led by Professor Abigail Nieves Delgado, Dr. Aline Potiron, and others, on how microbiome scientists define terms which are used to describe people, and how those definitions carry assumptions that may influence the interpretation of the results by researchers or readers.

Population descriptors are ways of, well, describing populations. However, the selection of terms, how you define them, how you categorize those terms, are often too strict to be applied to real-life people or in different communities. Using the same example of age, how do you compare age in two populations with wildly different exercise, diet, or stress load which all impact the physical or behavioral expression of age? More to the point of this talk, how do you categorize ancestry without nuance? Do you focus on genomics, or culture, or both? Do you place people in categories based on certain factors, or let them choose their own? How do you compare people in one location to another without considering the history of war, colonization, and slavery had on the ability of people to choose with whom to have children? And does ancestry even matter when you consider the myriad changes to health and the microbiome effected by what you eat, what animals and people you interact with, and where you live? Scientists all working on the human microbiome had wildly different understanding or definitions of population descriptors, and beliefs around what population descriptors were caused by or caused changes to the microbiome. And this, despite most microbiome studies having little to no need for information on ancestry or race to answer their research question.

Studies don’t gather data on every possible factor in people, that would require a detailed biography of every participant. Researchers choose what type of data to collect about someone based on what is important to the study and answering the research question – but as researchers we tend to think within the constraints of our own discipline – what info do I need for my statistics or to publish in my field? When that happens, we compress the variability of the people we study into fewer dimensions, example like taking an in-person experience at the beach and representing it as the words “seashells”, “gritty floor”, and “wet”.

Finally, a theme that came up several times during the workshop was that human social structure or institutions sometimes have so many constraints as to fail in their mission to provide resources to the public. As a perfect example, we did not have air conditioning at the university, even though was 85 degrees outside and between 90 and 105 degrees F inside some of the rooms after we had been in them for a while, because it is university policy to turn air conditioning on for the whole campus only after a certain date regardless of what is going on in real life. I don’t want to pick on the university, because this is a very common policy at universities, including UMaine. But it highlights the point that solutions (to air conditioning, microbiomes, health, etc.) need to be nimble enough to respond to local conditions using the input of people who are actually living through those conditions. And in this way, we have the crux of the workshop: how do we perform local-conscious and nimble science that is driven by the needs of actual living things or ecosystems, against the tide of institutional habit? For me, that’s going to involve more community-based and person-driven research questions, more collaboration with this remarkable group of researchers, and hopefully a lot more fresh, Italian mozzarella.

Diagram illustrating effects of biodiversity on microbial communities and plant health. Top section shows diverse ecosystem with various plants and animals leading to diverse microbes that produce reactive oxygen species (ROS) and suppress pathogens, enhancing plant resistance; bottom section shows less diverse ecosystem with fewer microbes, reduced ROS, and increased pathogen susceptibility.

Paper published on preserving microbiomes to secure health in degrading ecosystems!

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I’m delighted to announce a new publication on the importance of preserving microbiomes to secure health in degrading ecosystems! The paper outlines strategies for preserving critical microbes, functions, and microbial communities using some specific examples, and ties these back to opportunities and challenges to making conservation efforts.

This paper was a collaborative effort by several members of the Microbiome Stewardship team, Panuya Athithan (grad student working with Emma), Kieran O’Doherty (fearless leader of the MiSt group), Emma Allen-Vercoe (maven of the human microbiome), and myself. Panuya and I led the paper, weaving our favorite stories of microbial symbioses together with existing studies that support the need for stewardship. Panuya is currently a PhD student working with Emma on a variety of projects, including a gut microbiome and early life project she was interviewed about here. She’s also a Young Director at the non-profit Fora: Network for Change, and was previously an undergraduate researcher while at the University of Waterloo.

A little over a year ago, the author team was discussing the need for papers which outline examples of critical host-microbial or ecosystem-microbial partnerships which are irreplaceable (unless you have several million years of free time to wait for evolution), as a means of supporting calls for taking action now to preserve life and ecosystems on what is currently the only planet we call home.

Left to right; front: Zhongzhi (Michael) Sun, Emma Allen-Vercoe, Sue Ishaq; middle: Mikaela Beijbom, Mallory Choudoir, Sarah Elton, Kieran O’Doherty, Panuya Athithan; back: Grace Gabber, Andreas Heyland, Rob Beiko.

Over a series of conversations with the MiSt group, as well as during the first public meeting to create the IUCN Microbe Specialist Group, our author team honed our paper to address the concerns of researchers over the ability and practicality of stewardship microbes.

Left to right in the photo are some of the MiSt group; front: Zhongzhi (Michael) Sun, Emma Allen-Vercoe, Sue Ishaq; middle: Mikaela Beijbom, Mallory Choudoir, Sarah Elton, Kieran O’Doherty, Panuya Athithan; back: Grace Gabber, Andreas Heyland, Rob Beiko.

This paper is one of the first in a forthcoming special issue (announcement coming soon!), which will feature several invited papers from my microbiome stewardship colleagues (both original team and expansion pack researchers). These papers will expand upon the concept of what it means to share microbes between individuals, communities, and ecosystems; what it would mean to consider microbes as shared natural resources to which everyone had an innate right to; and how it would look for public and planetary health to reduce the harm of human industry and consumerism to live more sustainably and regain all the benefits that the microbial world can provide us.

Microbes first into the life rafts: preserving microbiomes to secure health in degrading ecosystems

Click here to check out the paper

Authors: Panuya Athithan 1,2*, Suzanne L. Ishaq 2,3,4*, Emma Allen-Vercoe 1,2 Kieran C. O’Doherty 2,4,5

  • 1 Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, N1G 2W1
  • 2 The Microbiome Stewardship research group
  • 3 School of Food and Agriculture, University of Maine, Orono, Maine, 04469
  • 4 The Microbes and Social Equity working group, Orono, Maine, 04469
  • 5 Department of Psychology, University of Guelph, Guelph, Ontario, N1G 2W1

Abstract

All organisms on the planet intrinsically rely on microbial ecosystems, and there are increasing calls from research communities to consider microbiota when administering personal or public health, ecosystem health, and the use of microbiota in personal or environmental health remediation, such as reducing the impacts of climate change, or protecting at-risk habitats which host rare microbiota. Through our collective work on the integral nature of microbiomes to host and environmental health, on health policy, and on the development of research and policy agendas, we have previously developed the concept of ‘microbiome stewardship’ and guidelines to promote consideration of microbial communities broadly or in specific scenarios. The practicality of stewarding one versus many microbiota is highly contextual, and will require different strategies for different scales of conservation. Here, we provide scientific arguments for the need for microbial stewardship, examples of possible solutions scaled to different ecological challenges or conservation goals, discourse on the logistical challenges which have been cited by research communities, and opportunities to use cutting-edge microbiome concepts and technology to implement large-scale interventions.

Sustainability Statement

Microorganisms are responsible for environmental and organismal health, and the stewardship of microbiota has applications for human, plant, animal, and environmental health on local and global scales. The concepts described here are pertinent, in particular, to the United Nations’ Sustainable Development Goal 3) good health and wellbeing. Additionally, our paper is relevant to goals 6) clean water and sanitation, 9) industry, innovation, and infrastructure, 11) sustainable cities and communities, 12) responsible consumption and production, 13) climate action, 14) life below water, 15) life on land, and 17) partnerships for the goals.

Diagram illustrating examples of microbial-host or microbial-ecosystem interactions which illustrate the need for microbiome stewardship, including preservation of ecosystems, functions, or niches. The interaction between bobtail squid and their symbiont bacteria is used as an example of a specific niche that cannot be replaced with another host or bacteria. The interactions between bacteria providing metabolites for a coral host exemplifies the need to protect microbial community functions. The interaction between two bacteria involving one bacteria blocking reactive oxygen species so another bacteria survives and sequesters carbon is used as an example of the need to protect whole ecosystems to allow this process to occur.
Graphical abstract: The concept of microbiome stewardship can be applied at multiple scales to provide guidance on both specific or general microbial interactions. Graphic made in Biorender under licence.

Advocating for science on Capitol Hill

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Advocating for science on Capitol Hill

Last week, while I was in D.C. for a Board of Directors’ meeting for the American Society of Microbiology, I had the opportunity to attend an ASM Hill Day. Led by the ASM Public Policy and Advocacy Team, Hill Days bring scientists to Capitol Hill to advocate for science by sharing our lived experience of federal funding functions. This time, several members of the ASM Board spoke with U.S. legislators’  offices about the health, environmental sustainability, and economic development priorities of the microbial scientific community, scientific funding in the next fiscal year, and how microbiologists around the world are eager to provide scientific evidence to inform public policy. On a more somber note, we brought personal stories about the effects of disruptions to research and education last year; the disruptions to education funding and loss of students who can’t afford to continue their academic and professional training; the effect of stalled payments on funding projects this year; and more.

Four people in suits posing for a selfie in front of the US Capitol Building.

I was on a team led by Senior Federal Affairs Officer Nicole Zimmerman from the ASM Policy Team, along with incoming ASM President-Elect Dr. Federico Sisti, and current ASM President Dr. Alexander McAdam.

ASM is always looking for members who would like to learn how to advocate for science, share their stories with lawmakers, and help shape the future of science policy. You can find out more about recent advocacy from the ASM Policy Action Center, and specifically hear about ways to get involved iin the Action Network. Earlier in my career, I never thought I would be interested in getting involved in policy, or confident enough to advocate on behalf of 38,000 microbiologists, but the ASM Policy Training made it really easy for me to identify needs or concerns from my colleagues and students, collect data to demonstrate the impact of policies on our industry, and specify steps that legislators could take to seize opportunities or provide resolutions. With the global social, political, and economic turmoil we have all been facing for years– to put it mildly – having the opportunity to be a small part of building the future has been a meaningful part of my career. I highly recommend it!

Offering expertise and building trust

One of the messages that we were keen to share with US (and all) policymakers, articulated by incoming ASM President-Elect Dr. Federico Sisti, is that ASM members around the world have an incredible breadth and depth of expertise in all topics related to microbiology, and that we are here to help. ASM has always had a strong initiative for providing scientific information and policy support, including ASM policy staff and our thousands of members.

A person in a suit standing outside the DC office for Senator Angus King.

But, to create the collaborations between scientists and policy makers requires time to build trust and establish regular communication. Here, I had an advantage in that 3 of my meetings were with Maine lawmakers (Senators Angus King and Susan Collins, and Representative Jared Golden), and being a voting constituent lends weight to my voice as I spoke about how reduction in funding for education, and disruptions to research funding which also impacted student research opportunities, impacted students and communities in Maine.

From the classroom to Congress

Serendipitously, I know one of the staff members in Senator Susan Collins’ office, and it was a delightful surprise to run into Michael DeLorge, co-Valedictorian at UMaine in 2024 and student in my Intro to Animal Microbiomes class. My microbiomes class talks about the need for science in policymaking, as well as the need for diverse and far-reaching collaborations in order to solve global challenges, such as those set out by the United Nations Sustainable Development Goals.

Two people in business suits posing for a photo in an office.

I got even further into the connection between research and public policy, as well as federal funding, in my Capstone In Animal Science course, nicknamed “How To Be A Researcher”. I have a whole lecture about the federal funding process in the US, historic funding levels, and how agencies had been trying to improve equity in the distribution of funds (including to rural areas, primarily undergraduate institutions, and other universities which had received less research and education funding).

I also teach my students about designing impactful research by identifying problems to solve and the relevant impacted communities (humans, animals, plants, other organisms, ecosystems). Over the semester, students design research projects and detail them in funding proposals, but we write them backwards by first identifying who/what the students want to help, then identifying the problem or what they could help with, and then outlining the strategy for finding information so we could make a positive change.

And, I’m sure my Capstone students will be happy to hear that I put into practice what I make them do in the classroom: all of my meetings on Capitol Hill were essentially “Elevator Speeches”, short pitches which identify a problem and a possible solution in a succinct format that allows the listener to engage in a discussion with you. I’m happy to report that I kept all my speeches under the meeting time limit 😊

The views expressed in this post and in my meetings were my own and did not represent the institutions I am affiliated with.

Article published on the efficiency of a glucoraphanin supplement, and the gut microbial response!

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The Lab is delighted to finally announce the publication of a study on the efficacy of a glucoraphanin supplement in converting to sulforaphane, and of the effect on or participation of gut microbes! The article can be found online here.

The study was run back in 2021 at Appalachian State University by Dr. Giuseppe Valacchi, Alessandra Pecorelli, and colleagues, when participants were given one dose of a glucoraphanin supplement combined with the plant enzyme myrosinase (which converts the GLR into the anti-inflammatory sulforaphane by the time the supplement gets to your small intestines), or one dose of the glucoraphanin supplement alone (in the absence of the plant enzyme, this requires gut microbes to convert GLR to SFN).

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.

Since the Ishaq Lab is interested in how gut microbes can produce anti-inflammatories from inactive compounds in broccoli sprouts, and the Li Lab has been researching the use of sulforaphane for disease prevention and treatment for almost 20 years, Yanyan and I were a natural fit for this collaboration.

Yanyan and I were introduced to Dr. Jed Fahey when he joined the UMaine Institute of Medicine faculty network in 2022. We talked to Jed about his recent work Brassica Protection Products, a company he founded back in 1997 with Dr. Paul Talalay, and Yanyan and I were invited as collaborators in 2023 by Antony Talalay, CEO and Co-Founder, and Paul’s son.

As part of their dissertations, Marissa Kinney performed qPCR to quantify microbial genes during her master’s, and Lola Holcomb performed 16S rRNA bacterial community sequencing during her PhD. We submitted the manuscript for peer review in Dec 2024. After a slow review process, the paper was finally released in Feb 2026, and we’ve begun brainstorming the next step in our research. While Jed, Tony, and the BPP team are, of course, interested in how their supplement can be used to improve health, the Ishaq Lab is also interested in teasing apart why some people’s gut microbiome is very responsive to GLR supplementation and will produce a fair amount of sulforaphane, while other’s people’s gut won’t react to glucoraphanin at all.

Even more intriguing were the participants in the study who had very little glucoraphanin conversion even when the myrosinase enzyme that can do the conversion was provided in the supplement. In fact, there was a lot of variability in how effective the enzyme was depending on the person- implying there are other biological or environmental factors at play which may be impeding the conversion of glucoraphanin into an anti-inflammatory.

Exogenous myrosinase from mustard seed increases bioavailability of sulforaphane from a glucoraphanin-rich broccoli seed extract in a randomized clinical study.

Angela Mastaloudis, Lola Holcomb, Jed W. Fahey, Camila Olson, David C. Nieman, Colin Kay, Robert O’Donnell, Alessandra Pecorelli, Marissa Kinney, Yanyan Li, Suzanne L. Ishaq & Giuseppe Valacchi. Scientific Reports, In Press.  (2026) 

Abstract: Inactive glucoraphanin (GR) in broccoli is converted to the antioxidant, anti-inflammatory, and anti-bacterial sulforaphane (SF) by cruciferous vegetable enzyme myrosinase (Myr), or similar enzymes from specific gut bacteria; both sources have variable efficiency. The effects of exogenous Myr on the conversion efficiency of GR to SF was compared to gut microbial Myr-like activity. In a randomized, double-blind, crossover study, sixteen subjects (9 F: 7 M) received a single oral dose of GR in broccoli seed extract with Myr-containing mustard seed powder, or broccoli seed extract alone, both with ascorbic acid. GR + Myr, on average, doubled the bioavailability of SF (39.8 ± 3.1%) compared to GR alone (18.6 ± 3.1%), and increased the conversion rate in the first 8 h (25.4% ± 2.7%) compared to GR alone (8.0% ± 2.7) based on measurement of urinary metabolites. There were no differences in fecal bacterial communities after the single dose; however, four bacterial GR-converting genes significantly correlated with GR conversion (p < 0.0155). To our knowledge, this is the first human study to simultaneously investigate (1) a well-defined Myr source, (2) broccoli seeds as source of GR, (3) prediction of gut microbial responsiveness to GR.

Lola begins a postdoctoral research position in bioinformatics at the University of New England!!

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We’re thrilled to share that Dr. Lola Holcomb, who recently completed her PhD in Biomedical Science at the University of Maine, will be joining Dr. Eben Estell’s lab at the University of New England as a Postdoctoral Research Fellow! Dr. Estell is a new faculty member starting up a lab developing tissue engineered models for bone mechanobiology, and this position will focus on data analysis and conceptual models on how cells interact with mechanical structures, to create better medical treatments.

During her doctoral work in the Ishaq Lab, Lola investigated how diet and gut microbiota interact to influence host health, with a particular focus on glucosinolate-metabolizing bacteria and the effects of broccoli sprout consumption. Her research combined bioinformatics, metagenomic data analysis, and microbial ecology, resulting in new insights into how diet-driven changes in microbial function relate to host physiology.

In her postdoctoral position, Lola will be bridging her bioinformatics expertise with her original background in exercise physiology to explore how mechanical loading, irisin, and bone cell biology are interconnected. This new role beautifully integrates her computational skills with her passion for physiology and health — a truly interdisciplinary continuation of her scientific journey.

One of Lola’s favorite memories from her time in the lab was traveling together to the ISME conference in Cape Town, where she presented her work to an international audience of microbial ecology researchers. It was a fantastic milestone that captured her growth as both a scientist and communicator.

We can’t wait to see where Lola’s research takes her next! Luckily, Lola will still be collaborating a bit with the Ishaq Lab to finish out several projects from her doctoral work. This includes genomic comparisons of bacteria which can convert glucoraphanin into sulforaphane, metagenomics of the gut bacteria of people consuming broccoli sprouts every day for a month, and several collaborations on human microbiome research.

Co-written by Lola Holcomb and Sue Ishaq.

Article published on the use (and mis-use) of human population descriptors as biological determinants of human microbiomes!

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Since the summer of 2023, I have been part of an interdisciplinary team that examines the way microbiome researchers use social and population descriptors for people in their analysis. In many cases, only basic information about a person is available in large datasets that are publicly available to use, or detailed information about a person is difficult to obtain during a study, thus many researchers rely on “proxy terms” to try and understand how human microbiomes are assembled and changed. Proxy terms are broad categories that group people, such as geographic area or race, but often these are too broad to be used for any meaningful analysis, especially when working with biological data.

‘Race’ is a relatively new concept used to describe social groups, and as discussed brilliantly in the National Academies of Science, Engineering, and Medicine’s report on “Use of Race, Ethnicity, and Ancestry as Population Descriptors in Genomics Research“, it has been mis-used for several hundred years to insinuate basic biological differences between people. This was done intentionally to justify discrimination all the way up to slavery, but it has been unintentionally propagated into research through the use of race as a proxy term to represent someone’s lifestyle. In recent decades, microbiome research has been trying to understand how human lives affect the microbiomes they accumulate, and similarly has sometimes incorrectly espoused the idea that vague social categories manifest as biological differences.

Our group delved in the history of race in biological science, case studies where results that implicate race led to discriminatory policy and practice, and give guidelines for selecting more specific factors to understand the social and environmental impacts on the microbiome.

I’m pleased to announce that we just had our review published in mSystems: ” Prioritizing Precision: Guidelines for the Better Use of Population Descriptors in Human Microbiome Research.” We presented this work at the 2024 Microbes and Social Equity speaker series, too, and the recording can be found here. It builds off of our collective work over the past decade.

Nicole M. Farmer, M.D.,

Amber Benezra, PhD.,

Katherine Maki, PhD.,

Sue Ishaq, photo courtesy of Patrick Wine, 2021.

Sue Ishaq, PhD.,

Ariangela Kozik

Ariangela Kozik, PhD.,

“ Prioritizing Precision: Guidelines for the Better Use of Population Descriptors in Human Microbiome Research.“

Authors:  Nicole M. Farmer1,2, Amber Benezra1,3, Katherine A. Maki1, Suzanne L. Ishaq1,2, Ariangela J. Kozik1,2,4,5* 

Affiliations:

1 The Microbes and Social Equity working group, Orono, Maine, USA; 2 Nova Institute for Health, Baltimore, MD; 3 Science and Technology Studies, Stevens Institute of Technology, Hoboken, New Jersey, USA; 4 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA; 5 Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan, USA

Abstract

Microbiome science is a celebration of the connections between humans, our environment, and microbial organisms. We are continually learning more about our microbial fingerprint, how each microbiome may respond to identical stimuli differently, and how the quality of the environmental conditions around us influences the microorganisms we encounter and acquire. However, in this process of self-discovery, we have utilized socially constructed ideas about ourselves as biological factors, potentially obscuring the true nature of our relationships to each other, microbes, and the planet. The concept of race, which has continuously changing definitions over hundreds of years, is frequently operationalized as a proxy for biological variation and suggested to have a real impact on the microbiome. Scientists across disciplines and through decades of research have misused race as a biological determinant, resulting in falsely scientific justifications for social and political discrimination. However, concepts of race and ethnicity are highly nuanced, inconsistent, and culturally specific. Without training, microbiome researchers risk continuing to misconstrue these concepts as fixed biological factors that have direct impacts on our microbiomes and/or health. In 2023, the National Academies of Sciences, Engineering, and Medicine released recommendations on the use of population descriptors such as race and ethnicity in genetic science. In this paper, we posit similar recommendations that can and must be translated into microbiome science to avoid re-biologizing race and that push us toward the goal of understanding the microbiome as an engine of adaptation to help us thrive in a dynamic world.

Commentary published on Microbiome Stewardship!

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Our collaborative team of researchers (bioethicists (Kieran and Diego), bioinformaticians (Rob), host microbial ecologists (Sue and Emma), and soil microbial ecologists (Mallory), had our first co-authored paper published in mSystems! Our paper is a commentary on the concept and need for microbiome stewardship, and outlines the research and policy priorities that are the focus of our ongoing research.

Microbiome stewardship is the broad idea that when we think about the relevance of healthy microbiomes for public health, we need to consider ecosystem-level factors such, as environmental pollutants, built environments, industrial food processing that affect interactions between microbes and human health. Microbiomes are highly dynamic and complex systems, composed of  bacteria, archaea, protozoa, fungi, and viruses; and our personal microbiomes are derived from larger shared, collective microbial resources.

Microbiome scientists are increasingly demonstrating the importance of microbial ecologies for human and environmental health. In spite of this, no protections are in place to ensure the health of microbiomes. In other words, there are no policies protecting microbiomes, which in turn are foundational to the health of all environmental and host ecosystems.  We built our research team to develop a framework and definition for microbiome stewardship, guiding principles for its implementation, and tools for assessment. Last year, we were awarded funding from the Canadian Institutes for Health Research (CIHR) for a four-year project investigating how our collective microbiomes (the diverse microbes we share between humans and our environments) impact health! 
The publication of this commentary also sets the stage for a Summit on Pathways to Microbiome Stewardship which the research team is organizing for July 7-10, 2025.

Commentary

Choudoir, M., Ishaq, S., Beiko, R., Silva, D., Allen-Vercoe, E., O’Doherty, K. 2025. The case for microbiome stewardship: What it is and how to get there. mSystems. 0:e00062-25.  https://doi.org/10.1128/msystems.00062-25

Abstract:
Microbiomes are essential for human, animal, plant, and ecosystem health. Despite widespread recognition of the importance of microbiomes, there is little attention paid to monitoring and safeguarding microbial ecologies on policy levels. We observe that microbiomes are deteriorating owing to practices at societal levels such as pesticide use in agriculture, air and water pollution, and overuse of antibiotics. Potential policy on these issues would cross multiple domains such as public health, environmental protection, and agriculture. We propose microbiome stewardship as a foundational concept that can act across policy domains to facilitate healthy microbiomes for human and ecosystem health. We examine challenges to be addressed and steps to take toward developing meaningful microbiome stewardship.

Figure 1. Microbiome stewardship as a concept and framework for ensuring human and planetary health supported by microbial functions. Human microbiomes are constituted from our environment, which has determinants based largely on societal systems (e.g., agriculture and food systems, built environment, health care accessibility) that operate beyond individual choice and behavioral interventions. Figure created with BioRender.com.

Acknowledgments: We thank Lola Holcomb for their helpful feedback and organizational contributions to this manuscript.

Funding:
United States Department of Agriculture National Institute of Food and Agriculture Hatch Project Accession 7004439 (MJC)
United States Department of Agriculture National Institute of Food and Agriculture through the Maine Agricultural & Forest Experiment Station: Hatch Project ME022329 (SLI)
National Institute of Health (NIH/NIDDK 1R15DK133826-01) (SLI)
Canadian Natural Sciences and Engineering Research Council (RGB)
Canada Research Chairs program (EA-V)
Canadian Institutes of Health Research (Funding Reference Number: 191753) (KCO)
University of Guelph Institute for Environmental Research (KCO)

Meet the Team

A headshot of Dr. Kieran O'Doherty, PhD who is wearing a black pinstripe shirt and standing outside in front of a yellow brick wall.

Dr. Kieran C. O’Doherty, PhD., is professor in the department of psychology at the University of Guelph, where he directs the Discourse, Science, Publics research Group. His research focuses on the social and ethical implications of science and technology and public engagement on science and technology. He has published on such topics as data governance, vaccines, human tissue biobanks, the human microbiome, salmon genomics, and genetic testing. A particular emphasis of his research is on theory and methods of public deliberation, in which members of the public are involved in collectively developing recommendations for the governance of science & technology. Recent edited volumes include Psychological Studies of Science and Technology (2019) and The Sage Handbook of Applied Social Psychology (2019). He is editor of Theory & Psychology.

Dr. Rob Beiko, PhD., is a Professor and Head of the Algorithms and Bioinformatics research cluster in the Faculty of Computer Science at Dalhousie University. His research aims to understand microbial diversity and evolution using machine learning, phylogenetics, time-series algorithms, and visualization techniques. His group is developing software tools and pipelines to comprehensively survey genes and mobile genetic elements in bacterial genomes, and understand how these genomes have been shaped by vertical inheritance, recombination, and lateral gene transfer. He is also a co-founder of Dartmouth Ocean Technologies, Inc., a developer of environmental DNA sampling devices.

A headshot of Dr. Sue Ishaq, PhD in which she is wearing a black and white houndstooth pattern waistcoat and a white button up shirt. Graphics have been added to show a strand of DNA and the words "love your microbes"

Dr. Sue Ishaq, PhD., is an Associate Professor of Microbiomes, University of Maine; and founded MSE in 2020.  Over the years, her research has gone from wild animal gut microbiomes, to soils, to buildings, and back to the gut. Since 2019, her lab in Maine focuses on host-associated microbial communities in animals and humans, and in particular, how host and microbes interact in the gut and can be harnessed to reduce inflammation. She is also the early-career At Large member of the Board of Directors for the American Society for Microbiology, 2024- 2027. 

Dr. Emma AllenVercoe, PhD, is a Professor of Microbiology at the University of Guelph, and a Tier 1 Canada Research Chair in Human Gut Microbiome Function and Host Interactions. Her research portfolio is broad, encompassing host-pathogen interplay, live microbial products as therapeutic agents, gut microbiome and anaerobic culture (humans and animals), and the study of ‘missing gut microbes’ i.e. those that are present in hunter-gatherer societies but missing in the industrialized world.  She has developed the Robogut – a culture system that allows for the growth of gut microbial communities in vitro, and is currently busy a centre for microbiome culture and preservation at the University of Guelph.

Dr. Mallory Choudoir, PhD wearing a button up bro

Dr. Mallory Choudoir, PhD, is an Assistant Professor & Soil Microbiome Extension Specialist in the Department of Plant & Microbial Biology at North Carolina State University. The goal of her applied research and extension program is to translate microbiome science to sustainable agriculture. She aims to develop microbial-centered solutions for optimizing crop productivity, reducing agronomic inputs, and enhancing  agroecosystem resilience to climate change.

Diego Silva, PhD wearing a blue shirt and eye glasses and standing in from of a red brick wall.

Diego Silva, PhD, is a Senior Lecturer in Bioethics at Sydney Health Ethics and the University of Sydney School of Public Health. His research centers on public health ethics, particularly the application of political theory in the context of infectious diseases and health security, e.g., tuberculosis, COVID-19, antimicrobial resistance, etc. He is currently the outgoing Chair and a member of the Public Health Ethics Consultative Group at the Public Health Agency of Canada and works with the World Health Organization on various public health ethics topics on an ad hoc basis.

White paper and perspective published on “Running a queer- and trans-inclusive faculty hiring process”!!

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I’m delighted to announce the public release of a white paper on queer- and trans-inclusive faculty hiring practices, and a perspective piece introducing it!! This is the culmination of months of writing by an international group of talented scientists led by Dr. JL Weissman, and I was honored to participate in these and future efforts from the group.

The newly-formed group, Advancing Queer and Trans Equity in Science (AQTES), wants to improve the field of research by making the hiring process fair and welcoming for everyone. No matter what your personal identity is, we can all agree that fair and unbiased job searches are critical to hiring the best talent. But, sometimes a poorly-organized job search prevents the people with the best talent from applying at all.

In our white paper, we give suggestions on how to host a job search that is better for everyone. We provide examples and advice on how to write job adverts, create the agenda and atmosphere for the job search, how to make the interview process more accessible for everyone by remembering that we are humans and not robots, and how to support your new faculty.

Running a queer- and trans-inclusive faculty hiring process.

Authors

Weissman, JL, Chappell, C.R., Rodrigues de Oliveira, B.F., Evans, N., Fagre, A.C., Forsythe, D.,  Frese, S.A., Gregor, R., Ishaq, S.L., Johnston, J., Bittu, K.R., Matsuda, S.B., McCarren, S., Ortiz Alvarez de la Campa, M., Roepkw, T.A., Sinnott-Armstrong, N., Stobie, C.S., Talluto, L., Vargas-Muñiz, J., Advancing Queer and Trans Equity in Science (AQTES).

Abstract

Queer and transgender scientists face documented systemic challenges across the sciences, and therefore have a higher attrition rate than their peers. Recent calls for change within science have emphasized the importance of addressing barriers to the success and retention of queer and trans scientists to create a more inclusive, equitable, and just scientific establishment. Crucially, we note these calls come primarily from early career researchers; relatively few queer and trans scientists have passed through the gauntlet of the faculty job search to become faculty ourselves, which is typically key to long-term persistence in academia. Our lack of representation creates a self-reinforcing cycle in which queer and trans trainees do not see our needs considered in established processes and power structures. Moreover, this status quo has historically been and continues to be harmful, disproportionately impacting those of us who have multiple intersecting marginalized identities. Here, we provide concrete guidance to search committees to support queer and trans candidates throughout the faculty selection process based on our personal experiences as early career scientists who have been on the job market.

Graphics in the post and the article created by Callie R. Chappell.

Citations

Citation for the paper: Weissman, JL, Chappell, C.R., Rodrigues de Oliveira, B.F., Evans, N., Fagre, A.C., Forsythe, D.,  Frese, S.A., Gregor, R., Ishaq, S.L., Johnston, J., Bittu, K.R., Matsuda, S.B., McCarren, S., Ortiz Alvarez de la Campa, M., Roepkw, T.A., Sinnott-Armstrong, N., Stobie, C.S., Talluto, L., Vargas-Muñiz, J., Advancing Queer and Trans Equity in Science (AQTES). 2024. Running a queer- and trans-inclusive faculty hiring process. EcoEvoRvix repository 6791.

Perspective piece introducing the paper:  Weissman JL, Chappell CR, Francesco Rodrigues de Oliveira B, Evans N, Fagre AC, Forsythe D, et al. (2024) Queer- and trans-inclusive faculty hiring—A call for change. PLoS Biol 22(11): e3002919.

This work is being presented at the American Geophysical Union annual meeting in Washington DC in December, in the session on “ED12A: Advances and Progress Toward a More Inclusive, Diverse, Equitable, and Accessible Scientific Community II”.

This work is being presented as a seminar at the Microbes and Social Equity working group virtual seminar series, Dec 20th, 2024. Registration is free but required.

Paper published on “Early life exposure to broccoli sprouts confers stronger protection against enterocolitis development in an immunological mouse model of inflammatory bowel disease”

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The Ishaq and Li labs at UMaine are delighted to announce that our paper on “Early life exposure to broccoli sprouts confers stronger protection against enterocolitis development in an immunological mouse model of inflammatory bowel disease.” has been published in mSystems!! ASM was kind enough to write a press release about study, found here.

The complete author list, Abstract, and Ackowledgements/Funders portions of the paper can be found at the end of this post. This paper is part of a larger Broccoli project, in which we are evaluating the use of broccoli sprouts in the diet to enlist gut microbes to produce anti-inflammatories as a way to resolve symptoms of Inflammatory Bowel Disease.

The Premise

Broccoli sprouts are very high in a compound called glucoraphanin, which is in-active for humans. When glucoraphanin comes in contact with the myrosinase enzyme, also found in the sprouts, it is transformed into sulforaphane, which drives away insect pests but acts as an anti-inflammatory in people!

If you eat raw sprouts, most of this conversion happens when you cut or chew the sprouts, and that anti-inflammatory will get absorbed in your stomach. If you steam or cook the sprouts, you can inactivate the enzyme and leave the glucoraphanin compound alone. Some of your gut microbes are able to use glucoraphanin, and produce the anti-inflammatory sulforaphane right in your gut! We are trying to understand how and when this works, so we can use it to reduce symptoms of Inflammatory Bowel Disease.

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.
A cartoon of a woman eating broccoli, with the digestive tract shown on her shirt, and smiling microbes in the background.

The mice in this trial are used to mimic Crohn’s Disease, which is one of the main ways that Inflammatory Bowel Diseases may be classified. Crohn’s Disease is complictaed, and involves an over-active immune response to gut microbes. This is replicated in mice that are bred to lack the genes in the DNA to make interleukin-10 (IL-10). IL-10 is an immune factor that can be used to calm the immune system and tolerate microbes which are not causing harm. Without IL-10, these mice over-react to the presence of bacteria, even those which are not causing harm, and this creates symptoms similar to Crohn’s in people.

We used two age groups of mice, and in each group, half ate a mouse chow (control) diet and half ate the mouse chow with 10% of the chow replaced by raw broccoli sprouts. Crohn’s often develops in childhood and adolescence, so our two age groups of mice reflect the juvenile stage (4-5 weeks old) and the adolescence stage (5-6 weeks old) of symptom onset. After wo weeks of symptoms, we sacrificed the mice and collected as much information as we could.

Figure 1 from the paper mentioned in this post. It shows an experimental design.

The Team

The mice, their care during the experiment, and sample collection for this project was graciously provided by University of Vermont researchers Gary Mawe and Brigitte Lavoie, and then-grad-student-now-medical-student Molly Hurd, in 2021. The SUNY Bingamton team, Tao Zhang and Allesandra Stratigakis, processed metabolite and cytokine samples and analyzed those data. The UMaine team (pictured below and led by Sue Ishaq and Yanyan Li) processed and analyzed data from different locations of gut tissue for histolgy and sequencing of bacterial communities, as well as analyzing those data, and took the lead on writing the paper.

Portrait of Lola Holcomb, wearing a block sweater on a beach at sunset
Lola standing in front of her poster which displays the results of her research on gut microbes.
Louisa Colucci. Young woman with dark hair tied in a bun is sitting in a kayak with her paddle raised. She is wearing a black top and a red life-vest over it, in a light blue, single-person kayak. The kayak is in the water, most likely a lake, with the forested shoreline in the background.

The Health Benefits were most obvious in the younger mice

The mice that were eating the broccoli sprouts in their chow and did much better than the control group who ate only mouse chow when symptoms of Crohn’s Disease were induced — and we found something really interesting… The diet worked really well in the younger mice and reduced their symtpoms of inflammation and illness for almost every metric we studied. The older, adolecent mice got some benefit from eating the raw broccoli sprouts, but not nearly as much as the younger mice! Those graphs are shown in the paper.

The Gut Microbes were most changed in the younger mice

Bacterial richness (the number of different types of bacteria present) was increased, but only in younger mice consuming a 10% raw sprout diet, which is useful because pediatric Crohn’s patients usually have fewer types of bacteria present in their gut.

Younger mice consuming broccoli sprouts also had more types of bacteria that are known to convert glucoraphanin into sulforophane, and they had more of the genes needed to do it. Crohn’s patients usually have fewer of these types of bacteria, which are also known to provide other health benefits.

The Next Steps

We are currently working on replicating and expanding this project to include more age groups, so we can understand how different diet preparations of broccoli sprouts impact immune systems and gut microbiota at different developmental periods of life. We are also really interested in understanding how sex in mice, and gender in humans, plays a role in how immune systems and microbial communities develop during a critical phase of life. We have some initial data to suggest that male and female mice respond to different diets and at differnt ages, but we aren’t sure why yet.

We hope to expand our work with people to study how these diets work in the real world, and how we can tailor diet and cooking preparations of sprouts to best meet the needs of people of different ages, health statuses, and tastes.

The paper

Early life exposure to broccoli sprouts confers stronger protection against enterocolitis development in an immunological mouse model of inflammatory bowel disease. 

Lola Holcomb1$, Johanna M. Holman2$, Molly Hurd3, Brigitte Lavoie3, Louisa Colucci4, Benjamin Hunt5, Timothy Hunt5, Marissa Kinney2, Jahnavi Pathak1, Gary M. Mawe3,Peter L. Moses3,6, Emma Perry7, Allesandra Stratigakis8, Tao Zhang8, Grace Chen9, Suzanne L. Ishaq1*, Yanyan Li1*

1 Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, Maine, USA 04469. 2 School of Food and Agriculture, University of Maine, Orono, Maine, USA 04469. 3 Larner College of Medicine, University of Vermont, Burlington, Vermont, USA 05401. 4 Department of Biology, Husson University, Bangor, Maine, USA 04401. 5 Department of Biology, University of Maine, Orono, Maine, USA 04469. 6 Finch Therapeutics, Somerville, Massachusetts, USA 02143. 7 Electron Microscopy Laboratory, University of Maine, Orono, Maine, USA 04469. 8 School of Pharmacy and Pharmaceutical Sciences, SUNY Binghamton University, Johnson City, New York, USA 13790. 9 Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA 48109

$ these authors contributed equally.

Keywords: Crohn’s Disease, cruciferous vegetables, sulforaphane, glucoraphanin, gut microbiota, dietary bioactives, 16S rDNA, interleukin-10 knockout 

Abstract

Crohn’s Disease (CD) is a presentation of Inflammatory Bowel Disease (IBD) that manifests in childhood and adolescence, and involves chronic and severe enterocolitis, immune and gut microbial dysregulation, and other complications. Diet and gut-microbiota-produced metabolites are sources of anti-inflammatories which could ameliorate symptoms. However, questions remain on how IBD influences biogeographic patterns of microbial location and function in the gut, how early life transitional gut communities are affected by IBD and diet interventions, and how disruption to biogeography alters disease mediation by diet components or microbial metabolites. Many studies on diet and IBD use a chemically induced ulcerative colitis model, despite the availability of an immune-modulated CD model. Interleukin-10-knockout (IL-10-KO) mice on a C57BL/6 background, beginning at age 4 or 7 weeks, were fed a control diet or one containing 10% (w/w) raw broccoli sprouts, which was high in the sprout-sourced anti-inflammatory sulforaphane. Diets began 7 days prior to, and for 2 weeks after inoculation with Helicobacter hepaticus, which triggers Crohn’s-like symptoms in these immune-impaired mice. The broccoli sprout diet increased sulforaphane in plasma; decreased weight stagnation, fecal blood, and diarrhea associated; and increased microbiota richness in the gut, especially in younger mice. Sprout diets resulted in some anatomically specific bacteria in younger mice, and reduced the prevalence and abundance of pathobiont bacteria which trigger inflammation in the IL-10-KO mouse, e.g., Escherichia coli and Helicobacter. Overall, the IL-10-KO mouse model is responsive to a raw broccoli sprout diet and represents an opportunity for more diet-host-microbiome research.

Importance

To our knowledge, IL-10-KO mice have not previously been used to investigate the interactions of host, microbiota, and broccoli, broccoli sprouts, or broccoli bioactives in resolving symptoms of CD. We showed that a diet containing 10% raw broccoli sprouts increased the plasma concentration of the anti-inflammatory compound sulforaphane, and protected mice to varying degrees against disease symptoms, including weight loss or stagnation, fecal blood, and diarrhea. Younger mice responded more strongly to the diet, further reducing symptoms, as well as increased gut bacterial richness, increased bacterial community similarity to each other, and more location-specific communities than older mice on the diet intervention. Crohn’s Disease disrupts the lives of patients, and requires people to alter dietary and lifestyle habits to manage symptoms. The current medical treatment is expensive with significant side effects, and a dietary intervention represents an affordable, accessible, and simple strategy to reduce the burden of symptoms.

Acknowledgements: This project was supported by the USDA National Institute of Food and Agriculture through the Maine Agricultural & Forest Experiment Station: Hatch Project Numbers ME022102 and ME022329 (Ishaq) and ME022303 (Li); the USDA-NIFA-AFRI Foundational Program [Li and Chen; USDA/NIFA 2018-67017-27520/2018-67017-36797]; and the National Institute of Health [Li and Ishaq; NIH/NIDDK 1R15DK133826-01] which supported Marissa Kinney, Timothy Hunt, and Benjamin Hunt. Johanna Holman was supported by ME0-22303 (Li), and Lola Holcomb was supported by US National Science Foundation One Health and the Environment (OG&E): Convergence of Social and Biological Sciences NRT program grant DGE-1922560, and the UMaine Graduate School of Biomedical Science and Engineering.

Paper published on “Steamed broccoli sprouts alleviate DSS-induced inflammation and retain gut microbial biogeography in mice”!

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The Ishaq and Li labs at UMaine are delighted to announce that our paper on “Steamed broccoli sprouts alleviate DSS-induced inflammation and retain gut microbial biogeography in mice” has been published in mSystems!! The complete author list, Abstract, and Ackowledgements/Funders portions of the paper can be found at the end of this post.

This paper is part of a larger Broccoli project, in which we are evaluating the use of broccoli sprouts in the diet to enlist gut microbes to produce anti-inflammatories. You can read about the whole project here, with links to other resources.

The Premise

A cartoon of a bacteria eating broccoli and pooping out sulforaphane
Designed by Johanna Holman
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.

Broccoli sprouts are very high in a compound called glucoraphanin. When glucoraphanin comes in contact with the myrosinase enzyme, also found in the sprouts, it is transformed into a compound that acts an an anti-inflammatory in people!

If you eat raw sprouts, this conversion happens when you cut or chew the sprouts, and that anti-inflammatory will get absorbed in your stomach. If you steam or cook the sprouts, you can inactivate the enzyme and leave the glucoraphanin compound alone. Some of your gut microbes are able to use the compound, and produce the anti-inflammatory right in your gut! We are trying to understand how and when this works, so we can use it to reduce symptoms of Inflammatory Bowel Disease.

The Mouse work

In the winter of 2020-2021, we ran a 40-day study with 40 mice housed at UMaine. The mice were divided into 4 groups: “control” which ate the mouse chow, “control+DSS” which ate the mouse chow and had colitis induced by adding DSS (a salt laxative) to their drinking water, “broccoli” which ate the mouse chow with steamed broccoli sprouts mixed in, and “broccoli+DSS” which ate the mouse chow/steamed broccoli sprouts diet and had colitis induced by adding DSS (salt laxative) to their drinking water. This work was led by Johanna Holman, who was a master’s student at the time; Lousia Colicci, who was an undergrad at Husson University at the time and is applying to medical schools now; Dorein Baudewyns, who was an undergrad at Husson University at the time and is completing a graduate program in Psychology at UMaine; and Joe Balkan, who was completing his senior year of high school at the time and has since begin an undergrad degree in Biology at Tufts University where he is preparing for medical school.

Person in a research facility holding up their arm with a mouse on it. Person is wearing a hairnet, nitrile gloves, surgical mask, and a surgical gown. They are holding their left arm up to the camera to show off a mouse with dark brown fur sitting on their arm. In the background is a metal shelf with containers of research materials.
Johanna Holman, graduate researcher in the Ishaq Lab
Louisa Colucci. Young woman with dark hair tied in a bun is sitting in a kayak with her paddle raised. She is wearing a black top and a red life-vest over it, in a light blue, single-person kayak. The kayak is in the water, most likely a lake, with the forested shoreline in the background.
Louisa Colucci.
A person holding a mouse in a research facility. The person is wearing a hairnet, nitrile gloves, a surgical mask, and a surgical gown. The mouse with dark brown fur is sitting on the top of the person's hand. In the background, there are metal shelves with bins and containers of research supplies.
Dorien Baudewyns, undergraduate researcher at Husson University
Joe Balkan, performing culturing of bacteria at the anaerobic chamber. Joe is wearing a face mask, and is holding up a culture plate. There are stacks of petri dishes inside the chamber.
Joe Balkan, undergraduate researcher at Tufts University, performing culturing of bacteria at the anaerobic chamber.
Close-up image of a small, dark brown mouse perched on the arm of a graduate researcher. The person is wearing a face mask and surgical gown.

The mice were weighed regularly and fecal samples assessed for blood (signs of colitis). At the end of the study, the mice were euthanized so we could study the bacteria in parts of the intestines that we can’t access in humans. We used as few mice as possible, and got as much information from this study as possible, to do as much good as we can with their sacrifice.

The Health Benefits

As we’d hoped, the broccoli+DSS mice that were eating the broccoli sprouts that were given colitis did much better than the control+DSS group who ate mouse chow during their colitis. The broccoli+DSS mice were able to keep gaining weight as they grew, had better consistency of their stool, and had lower amounts of proteins and other metabolities in their blood which indicate inflammation (lower cytokines and lipocalin). Those graphs are shown in the paper.

The Gut Microbes

We found a lot of interesting things with the microbial communities that were living in different parts of the intestines, but the most exciting was that broccoli sprouts in the diet helped microbial communities stay alive in their original gut locations even during colitis! Certain microbes like to live in particular places in our intestines based on where different ingredients in our diet get processed, or the local environment (like how acidic the intestinal neighborhood is), and this is called biogeography.

In the graph below, our control group mice (eating chow) or the broccoli group (eating chow plus sprouts), we see that microbial communites in the small intestines clustered away from the microbial communities in the large intestines.

The DSS salt laxative, and ulcerative colitis, wreak havoc on gut microbes because they cause physical damage to the lining of the intestine, which where many microbes that can be useful to us live on or near. When we induced colitis in mice that were eating mouse chow (control+DSS group), the damage to the intestines caused a loss to some of the microbes living in different places. The remaining microbes that could survive these tough conditions were basically the same ones regardless of where we we looked in the intestines.

But, if mice had colitis and were eating broccoli sprouts (broccoli+DSS), the microbes were able to survive in their original locations and preserved biogeography! This is important because where microbes live in the gut may determine if the beneficial things they make can help resolve IBD symptoms in specific locations in the gut.

Image by Johanna Holman, graph from the paper.

The Spatial Location of GLR-digesting-genes

Bejamin and Timothy Hunt are undergraduates in Biology who have been working on bioinformatics in the Ishaq Lab since December 2022 after completing Sue’s DNA Sequencing Data Analysis Class. They joined the DSS project to provide in-depth analysis on some of the sequences which matched bacteria that are known to convert GLR into the anti-inflammatory SFN, as well as analyze data comparing numbers of genes known to be involved in the process.

A cartoon of the intestines with bacteria of interest in the jejunum, ceculm and colon,
Cropped figure from the paper, made by Benjamin and Timothy.
Benjamin Hunt

The study of the bioproduction of SFN and its mucosal and luminal activity benefited from the biogeographical analysis of this study. It was interesting to note the extreme dominance of a Bacteroides species in the broccoli treatments. B. thetaiotaomicron was indicated based on BLASTN analysis and an evaluation of matching species but was not directly suggested by the dada-Silva taxonomy assignment. The indication of B. thetaiotaomicron suggested analyzing the presence of the operon BT2159-BT2156, which was generally minimally present (<100) but at relatively high counts (>100,000) in some samples. Significantly, the operon was found at locations where no Bacteroides were identified. We continue to reflect on the similarities and differences in the biogeography of bacterial abundance and operon presence highlighted in the different treatments of this study.

Benjamin and Timothy Hunt

The Next Steps

As part of this project, we cultured hundreds of bacteria from the intestines of mice to try and isolate some of the ones that turn glucroraphanin into sulforaphane. We have a large team of students and researchers participating on the culturing work, some of whom are pictured here. We’ll be providing plenty of updates on that project as we continue to process the bacteria this fall!

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The Paper

Steamed broccoli sprouts alleviate DSS-induced inflammation and retain gut microbial biogeography in mice.

Johanna M. Holman1, Louisa Colucci2, Dorien Baudewyns3, Joe Balkan4, Timothy Hunt5, Benjamin Hunt5, Marissa Kinney1, Lola Holcomb6, Allesandra Stratigakis7, Grace Chen8, Peter L. Moses9,10, Gary M. Mawe9, Tao Zhang7, Yanyan Li1*, Suzanne L. Ishaq1*

1 School of Food and Agriculture, University of Maine, Orono, Maine, USA 04469 2 Department of Biology, Husson University, Bangor, Maine, USA 04401 3 Department of Psychology, University of Maine, Orono, USA 04469 4 Department of Chemical and Biological Engineering, Tufts University, Medford, Massachusetts, USA 02155 5 Department of Biology, University of Maine, Orono, Maine, USA 04469 6 Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, Maine, USA 04469 7 School of Pharmacy and Pharmaceutical Sciences, SUNY Binghamton University, Johnson City, New York, USA 13790 8Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA 48109 9Departments of Neurological Sciences and of Medicine, Larner College of Medicine, University of Vermont, Burlington, Vermont, USA 0540110 Finch Therapeutics, Somerville, Massachusetts, USA 02143

Abstract: Inflammatory Bowel Diseases (IBD) are devastating conditions of the gastrointestinal tract with limited treatments, and dietary intervention may be effective, and affordable, for managing symptoms. Glucosinolate compounds are highly concentrated in broccoli sprouts, especially glucoraphanin, and can be metabolized by certain mammalian gut bacteria into anti-inflammatory isothiocyanates, such as sulforaphane. Gut microbiota exhibit biogeographic patterns, but it is unknown if colitis alters these or whether the location of glucoraphanin-metabolizing bacteria affects anti-inflammatory benefits. We fed specific pathogen free C57BL/6 mice either a control diet or a 10% steamed broccoli sprout diet, and gave a three-cycle regimen of 2.5% dextran sodium sulfate (DSS) in drinking water over a 34-day experiment to simulate chronic, relapsing ulcerative colitis. We monitored body weight, fecal characteristics, lipocalin, serum cytokines, and bacterial communities from the luminal- and mucosa-associated populations in the jejunum, cecum, and colon. Mice fed the broccoli sprout diet with DSS treatment performed better than mice fed the control diet with DSS, including significantly more weight gain, lower Disease Activity Indexes, lower plasma lipocalin and proinflammatory cytokines, and higher bacterial richness in all gut locations. Bacterial communities were assorted by gut location, but were more homogenous across locations in the control diet + DSS mice. Importantly, our results showed that broccoli sprout feeding abrogated the effects of DSS on gut microbiota, as bacterial richness and biogeography were similar between mice receiving broccoli sprouts with and without DSS. Collectively, this supports the protective effect of steamed broccoli sprouts against dysbiosis and colitis induced by DSS.


Importance: Evaluating bacterial communities across different locations in the gut provides a greater insight than fecal samples alone, and provides an additional metric by which to evaluate beneficial host-microbe interactions. Here, we show that 10% steamed broccoli sprouts in the diet protects mice from the negative effects of dextran sodium sulfate induced colitis, that colitis erases biogeographical patterns of bacterial communities in the gut, and that the cecum is not likely to be a significant contributor to colonic bacteria of interest in the DSS mouse model of ulcerative colitis. Mice fed the broccoli sprout diet during colitis performed better than mice fed the control diet while receiving DSS. The identification of accessible dietary components and concentrations that help maintain and correct the gut microbiome may provide universal and equitable approaches to IBD prevention and recovery, and broccoli sprouts represent a promising strategy.

Acknowledgements: All authors have read and approved the final manuscript. The authors thank Jess Majors, University of Maine, for her kind and detailed care of the mice during the trial, and for Ellie Pelletier for her informal review of the manuscript. This project was supported by the USDA National Institute of Food and Agriculture through the Maine Agricultural & Forest Experiment Station: Hatch Project Numbers ME022102 and ME022329 (Ishaq) and ME022303 (Li) which supported Johanna Holman; the USDA-NIFA-AFRI Foundational Program [Li and Chen; USDA/NIFA 2018-67017-27520/2018-67017-36797]; and the National Institute of Health [Li and Ishaq; NIH/NIDDK 1R15DK133826-01] which supported Marissa Kinney, Timothy Hunt, and Benjamin Hunt. Lola Holcomb was supported by US National Science Foundation One Health and the Environment (OG&E): Convergence of Social and Biological Sciences NRT program grant DGE-1922560, and through the UMaine Graduate School of Biomedical Sciences and Engineering.