The community of microbes that comprise the microbiome in the human digestive system are a source of endless fascination and research at Northeastern’s College of Engineering, sparking innovations from faster wound healing to autism therapy to the obesity epidemic.
Collaborative scientific projects to further technology and understanding to solve the world’s grand challenges are no new occurrence. The largest to date is the successful Human Genome Project (HGP)—an international effort begun in the 1990s to identify and map all of the genes in the human body.
On the heels of HGP’s success came the Human Microbiome Project (HMP) in 2008. This National Institutes of Health (NIH) initiative was intended to span just five years, with the goal of identifying and characterizing all the microorganisms found in both healthy and ailing humans. But HMP has continued at NIH and beyond, with scientists tackling current initiatives such as the role of the microbiome in conditions like preterm birth, irritable bowel disease, and the onset of Type 2 diabetes.
“The explosion of interest in gut health has come about since the realization that the condition of the microbiome has a direct relationship to a variety of health conditions,” says Rebecca Carrier, professor and associate chair of research for the Department of Chemical Engineering. “At Northeastern, we have a large focus on use-inspired research and practical applications, so this is a perfect opportunity to help explore what we can do to positively affect the health of future generations.”
The field of human microbiome research has grown exponentially in the last decade, with researchers, engineers, and scientists from Northeastern tackling the thousands of microbes in the human body that out-measure our own genetic material, and discovering just what effect they have on our current and future health.
Rebecca Carrier: In vitro study of gut inflammation and mental health
As part of a collaborative project between Northeastern, MIT, and Boston Children’s Hospital, Professor Carrier is leading a $5 million NIH Bioengineering Research Partnership grant to develop an in vitro human model of the interactions between microbes and immune cells in the gut and other organ systems.
“Interactions between the epithelium (the tissues that line the intestine and other organs in the body), the microbiome, and immune cells have been observed, but aren’t well understood,” says Carrier. “Seventy percent of the body’s immune cells are found in the gut, so by learning more about the relationships between the gut and the rest of the human body—particularly those associated with inflammation—we can potentially prevent or develop therapies to treat a host of diseases.”
Carrier and her collaborators have been largely focused on the gut side of the interaction, having already published studies on the gut-liver connection. Fellow microbiome researcher and NIH grant recipient Abigail Koppes, assistant professor of chemical engineering, is working with Carrier and her colleagues on the integration of nerves crucial in the gut-brain connection, creating a simulation of this interaction in a dish by culturing nerve cells adjacent to epithelium, mimicking the anatomical location of nerve cells in gut tissue in the body. The nerve cells can thus sense signals sent from the epithelium and microbiome, and vice versa.
Ultimately, the plan is to incorporate multiple nerve cell types that are responsible for forming neural pathways that act as physical connections between the gut and the brain.
“Right now, there is no other in vitro way to study the real-time impact of the microbiome on human health like you can with ‘guts-on-a-chip’ models. Most of the work in the field is done in rodents, and any human studies usually involve analysis of the microbes present in feces, which only tells part of the story.”
The challenge Carrier and her team struggle with is to maintain the perfect conditions to keep both the gut microbes and the mammalian cells happy—something that happens constantly inside the human body, but is very difficult to attain inside a lab.
“Trying to mimic the actual environment in the intestine—including the digestive enzymes and low oxygen levels required for some microbes to survive, which can actually kill the other cells you’re trying to work with—is very challenging. But, by perfecting our culture systems to allow analysis of crosstalk between the microbiome and the mammalian cells in the gut, we’ll ultimately have a model gut system that can allow study of the interactions between the gut and the brain. Such a tool would be highly useful in development of strategies to prevent or treat disease states that have been linked to gut inflammation, including autism, Alzheimer’s, and depression.”
Abigail and Ryan Koppes: The connection between gut and neural health
Assistant Professor Abigail Koppes completed her post-doctoral study with Professor Carrier as an NSF ADVANCE Future Faculty Fellow and is closely linked to her human gut epithelial-microbiome-immune axis study. Now, Koppes and Chemical Engineering Assistant Professor Ryan Koppes are undertaking their own study on gut-brain communication, having recently been awarded a three-year, $632,000 Trailblazer New/Early Career Investigator R21 Award from the NIH National Institute of Biomedical Imaging and Bioengineering.
The Koppes’ teams are working on a “body on a chip” model to mimic certain aspects of the brain and gut that leverage the whole nervous system—the central nervous system (CNS), which includes the brain, spinal cord, and peripheral nerves that run to our extremities, and the autonomic nervous system (ANS), which regulates involuntary vital functions like breathing, blood flow, and the “fight or flight” response.
Working with researchers at Boston Children’s Hospital and Harvard Medical School, the team is trying to understand more about the enteric nervous system—a part of the ANS that controls gut function—and how it communicates with and regulates the digestive system.
“There are more neurons in your gut than in your spinal cord,” says Abigail, “but the area is vastly understudied. We’re developing new technologies to create bigger and more complex model systems that incorporate key aspects of the enteric nervous system and cells from the intestines.”
Much like Carrier’s research, one of the hardest parts of the study is trying to replicate the conditions that allow for the specific neural pathways that connect the brain and the gut to communicate outside of the human body.
“Working with these models is a bit like taking a computer, smashing it to pieces, putting it in a dish, and trying to get it to run and connect to Facebook,” jokes Ryan. “But, by simplifying the nervous system on a chip, we hope to better understand and mimic the complexity of the human body and how nerves impact organ function.”
The long-term goal of the Koppes’ project is to use these platforms to identify certain types of nutrients and metabolites that can reestablish normal function, such as a probiotic that can help ease depression and/or anxiety symptoms or minimize the inflammation caused by irritable bowel syndrome (IBS).
Ameet Pinto: Microbes found in water and their impact on health
For his part, Ameet Pinto, assistant professor in the Department of Civil and Environmental Engineering, is looking at microbes that begin outside of the human body: Pinto’s research is focused on microbial communities in drinking water.
With support from the National Science Foundation (NSF) and the Water Research Foundation (WRF), Pinto uses genomics and DNA sequencing to help identify unknown microbes in water in minutes to hours, not days. He and his team focus on microbes that are unregulated, some of which can cause health issues in those with compromised immune systems, from gastrointestinal to respiratory infections.
“When I started my post-doctoral work in drinking water engineering in 2009, we could spend days trying to characterize DNA sequences for 100 microbes,” says Pinto. “The technology has become so much more advanced that we can characterize millions in the same amount of time. It’s these advancements that make the microbiome much more accessible to researchers like myself and my colleagues.”
While water utility companies treat water to the height of federal and state regulations, the challenge is trying to predict what will come out of your tap at home after it has traveled through hundreds to thousands of miles of pipeline. Utility companies try to control for these unknowns by sampling at locations throughout their pipeline system, but it takes two to three days to test these samples, and by then, the population has already consumed the water.
That’s where handheld DNA sequencers come in. Perfected in the lab, being tested in the field, and perhaps available for home use soon, this portable technology allows for real-time testing of water samples for continuous monitoring.
“We want to get to the point where we can predict a water contamination event instead of waiting until the problem has been recognized because it is already effecting people,” says Pinto.
Ed Goluch: The measurement and control of microbes within the body
Chemical Engineering Associate Professor Edgar Goluch is the self-described “device guy.” His main area of expertise lies in creating the hardware and diagnostic tools that other researchers need to find the answers they seek.
Able to create sensing devices as small as a single bacteria cell, Goluch and his team focus much of their efforts on developing tiny sensors capable of measuring chemicals in real-time.
From what happens when someone eats turkey and its amino acid tryptophan comes into contact with bacteria in the gut, to what exact chemicals from bacterial processes prevent chronic bed sores from healing, Goluch has been working with microbiome researchers for nearly a decade, including Carrier, the Koppes, and Pinto.
“Right now, we’re working with the Center for Vascular, Wound Healing & Hyperbaric Medicine at Tufts Medical Center to help them measure the molecules that bacteria produce. The hope is to be able to predict what kind of infection a person could develop to be able to intervene at an earlier stage,” says Goluch.
Working with the Barabasi Group at Northeastern, which received a grant from One Brave Idea, Goluch is developing swallow-able technology to help assess whether the chemicals in the food a person eats can affect their chances at developing heart disease.
“With these chemical sensors on a pill, we can measure any chemical a researcher is interested in, from antioxidants to lipids, to see how the food people eat affects their disease state long-term. Not only that, but we’re looking into how many different chemicals we could measure with just one pill. One hundred? One thousand? Time will tell as both the technology and our understanding continues to grow, and that’s the exciting part of our research.”