IBS Biomarkers and Diagnostic Diapers With Maria Eugenia Inda-Webb

Dr. Maria Eugenia Inda-Webb, Pew Postdoctoral Fellow working in the Synthetic Biology Center at MIT builds biosensors to diagnose and treat inflammatory disorders in the gut, like inflammatory bowel disease and celiac disease. She discusses how “wearables,” like diagnostic diapers and nursing pads could help monitor microbiome development to treat the diseases of tomorrow.   Subscribe (free) on Apple Podcasts, Spotify, Google Podcasts, Android, RSS or by email. Ashley's Biggest Takeaways Biosensors devices that engineer living organisms or biomolocules to detect and report the presence of certain biomarkers.   The device consists of a bioreceptor (bacteria) and a reporter (fluorescent protein or light). Inda-Webb’s lab recently published a paper in Nature about using biosensors (Sub-1.4 cm3 capsule) to detect inflammatory biomarkers in the gut. The work is focused on diagnosing and treating inflammatory bowel disease, but Inda-Webb acknowledged that that is a large research umbrella. The next step for this research is to monitor the use of the biosensor in humans to determine what chemical concentrations are biologically relevant and to show that it is safe for humans to ingest the device. It is believed that the gut microbiome in humans develops in the first 1000 days to 3 years of life. Early dysbiosis in the gut has been linked to disease in adulthood. However, we do not have a good way to monitor (and/or influence) microbiome development. Inda-Webb hopes to use biosensors in diapers (wearables) to monitor microbiome development and prevent common diseases in adulthood. In 2015, Inda-Webb became ASM’s first Agar Art Contest winner for her piece, “Harvest System.” Inda-Webb is the 2023 winner of the ASM Award for Early Career Environmental Research, which recognizes an early career investigator with distinguished research achievements that have improved our understanding of microbes in the environment, including aquatic, terrestrial and atmospheric settings. Learn More About ASM’s Awards Program Featured Quotes: We engineer bacteria to sense particular molecules of interest—what we call biomarkers—if they are associated with a disease. And then, we engineer a way that the bacteria will produce some kind of molecule that we can measure—what we call reporter—so that could be a fluorescent protein or light, like the one that we have in this device. The issue is that inflammation in the gut is really very difficult to track. There are no real current technologies to do that. That is like a black box. And so, most of what we measure is what comes out from the gut, and has its limitations. It doesn't really represent the chemical environment that you have inside, especially in areas where you're inflamed. So, we really needed technologies to be able to open a window in these areas. The final device that I am actually bringing here is a little pill that the patient would swallow and get into the gut. And then they engineer bacteria that the biosensors, will detect, let's say, nitrous oxide, which is a very transient molecule. And the bacteria are engineered to respond to that in some way—to communicate with the electronics that will wirelessly transmit to your cell phone. And from there, to the gastroenterologist. We make the bacteria produce light. If they sense nitrous oxide, they produce light, the electronics read that, and the [information] finally gets into your phone. Part of the challenge was that we needed to make the electronics very very tiny to be able to fit inside the capsule. And also, the amount of bacteria that we use also is only one microliter. And so, imagine one microliter of bacteria producing a tiny amount of light. Finally, the electronics need to be able to read it. So that has been also part of the challenge. In this case, you have 4 different channels. One is a reference, and then the other 3 are the molecule of your choice. So, for example, what we show in the paper here is that we can even follow a metabolic pathway. So, you can see one more molecule turn into the other one, then into the other one. I'm really excited about that. Because normally we kind of guess as things are happening, you know, but here you can see in real time how the different molecules are changing over time. I think that's pretty exciting for microbiologist. The immediate application would be for a follow up. Let's say the patient is going to have a flare, and so you could predict it more much earlier. Or there's a particular treatment, and you want to see what is happening [inside the gut]. But for me, as a microbiologist, one of the things I'm most excited about will be more in the longer term. One of my favorite experiments that I do with the students is the Winogradsky column, and everyone gets super excited. So, we all have nice feelings for that. And it’s basically a column where we asked the students to bring mud from a lake, for example, and then some sources of nutrients. And then, after 6months, you will see all the layers, which is super pretty—beautiful, nice colors. But actually, that gives the concept of how the microenvironment helps to define where, or how, bacteria build communities. And so, what I think this device is going to do is to help us identify what is this microenvironment and to characterize that. And then, from there, to know if [an individual’s] microbiome is leaning towards the disease state, or if it's already in a serious or dangerous situation, to think about treatments that can lead to a more healthy state. So, I would just say it's really to have a window into the gut, and to be able to give personalized treatment for the patient. So, one application: I was thinking, I'm from the Boston area. So, one problem we have is getting a tick bite, right? After that, you could actually have to go through a very traumatic, antibiotic regime. I would imagine, in that case, you could [use the biosensor to] get the baseline [measurement], and then if you need to take these antibiotics, the doctors can follow how your microbiome is responding to that. Because one of the problems is that antibiotics changed the oxidation level [in the gut], and that really affects a lot the microbiome. To that point, for example, I get to know patients that they were athletes, and then, after antibiotic treatment, they have serious problems with obesity. Their life gets really messed up in many ways. And so, what I'm thinking is, if we could monitor earlier, there are a lot of ways that we could prevent that. We could give antioxidants; we could change the antibiotic. There are things that I think the doctor could be able to do and still do the treatment that we know. And of course, [although] we talk a lot about how much trouble antibiotics are, for certain things, we still need [them]. [The multi-diagnostic diaper] is one of my pet projects. I really love it. So yeah, basically, the issue is that the microbiome develops in the first 3 years. People even say like, 1000 days, you know. But there's really no way to monitor that. And now we're seeing that actually, if the microbiome gets affected, there are a lot of diseases that you will see in adult life. So, if we will be able to monitor the microbiome development, I really believe that we'll be able to prevent many of the diseases of tomorrow. What happens is that babies wear diapers. So, I thought it was really a very good overlap. We call that “wearables,” you know, like devices that you can wear, and then from there, measure something connected with health. So, in the diaper, I was excited because—different from the challenge with the ingested device, which was so tiny—here, we don't have the limitation of space. So, we could measure maybe 1000 different biomarkers and see how that builds over time. We can measure so many things. One could be just toxic elements that could be in the environment. I try to do very grounded science, and so, my question is always, ‘what’s the actionable thing to do?’ So, I'm thinking if there was a lot of toxicity, for example, in the carpet, or in the environment where you live, those are the easiest things to change, right? Then also, other things connecting more with the metabolism. [Often] the parents don't know that the kid has metabolic issues. So, before that starts to build and bring disease, it would be best if you could detect it as early as possible. From there, with symbiotics, we are thinking there are a lot of therapies that could engineer bacteria to produce the enzymes that the kid can’t produce. We could also [develop] other products, like for example, a t-shirt to measure the sweat. I'm also thinking more of the milk. I'm very excited about how the milk helps to build the microbiome in the right way. And that that's a huge, very exciting area for microbiologists. And so, we could also have nursing pads that also measure [whether] the mother has the right nutrients. My family, my grandparents were farmers, and in Argentina, really the time for harvest is very important. You can see how the city and really the whole country gets very active. And at that time [during a course Inda-Webb was taking at Cold Spring Harbor] in this course, I could see that with yeast we were having a lot of tools that would allow us to be much more productive in the field. And I thought, ‘Oh, this feels like a harvest system for yeast.’ Yes. So that was how it [Inda-Webb’s winning agar artwork, ‘Harvest System’] came out. I really love the people. Here, [at ASM Microbe 2023], I really found that how people are bringing so much energy and really wanted to engage and understand and just connect to this idea of human flourishing, right, giving value to something, and saying, ‘okay, we can actually push the limits of what we know.’ How beautiful is that? And you know, we can learn from that. That was very exciting. ASM Agar Art Contest Have you ever seen art created in a petri dish using living, growing microorganisms? That's agar art! ASM's annual Agar Art Contest is a chance for you to use science to show off your creative skills. Submissions Are Now Being Accepted! This year's contest theme is "Microbiology in Space." Head over to our Contest Details page to get all of the information about what you need to submit your entry. Submissions will be accepted until Oct. 28! Links for the Episode: Inda-Webb, et al. recent Nature publication: Sub-1.4 cm3 capsule for detecting labile inflammatory biomarkers in situ. Bacterial Biosensors: The Future of Analyte Detection. Let us know what you thought about this episode by tweeting at us @ASMicrobiology or leaving a comment on facebook.com/asmfan.