Gut Feeling

Over the past few decades, amid many marvelous medical advances, people appear to be getting sicker. Daily headlines announce the gravity of today’s “modern plagues” such as asthma, allergies, diabetes, obesity, autoimmune diseases, and cancer. It’s likely that you, someone in your family, or someone you know is managing one or more of these conditions. Unlike most lethal diseases of the past, which struck relatively fast and hard, these are chronic conditions that can diminish a person’s quality of life for decades.

Why are all these maladies rapidly rising? Is it mere coincidence? Could there be one underlying cause fueling these increases? These are just some of the provocative questions behind the Rutgers University Microbiome Program, one of many signature initiatives at Rutgers conceived to harness the university’s academic and research strengths for the purposes of improving the human condition and creating meaningful, global change.

The microbiome consists of the trillions of bacteria and other microorganisms living in and on human bodies, animals, plants, and our environment. The champions behind the Microbiome Program are Martin Blaser, Henry Rutgers Chair of the Human Microbiome and director of the Center for Advanced Biotechnology and Medicine; Maria Gloria Dominguez-Bello, Henry Rutgers Professor of Microbiome and Health and director of the New Jersey Institute for Food, Nutrition, and Health; and Liping Zhao, Eveleigh-Fenton Chair of Applied Microbiology. These experts believe multidisciplinary efforts to study, preserve, and restore the microbiome could play a significant role in staving off illness, prolonging the human health span, and creating healthier ecosystems.

“Because of modern life—sanitation, antibiotics—we’re changing the microbiome, and those changes have consequences,” says Blaser. “The ways that we have been changing the development of a normal microbiome in early life have moved us out of health and into disease.”

To address the challenges brought on by these changes, the program will promote the preservation of microbiome diversity and foster the development of new solutions for restoring and maintaining healthy microbiota. It also will train students to be the next generation of physicians and scientists in microbiome research and accelerate the translation of scientific discoveries to products and practices that improve global wellness.

Save the microbes

“We all know that the microbiome is important for our health,” says Dominguez-Bello. “We know that our genes are regulated by the microbiome, that our gene functions are interacting with microbes, that our microbes dictate a lot of what our immune and metabolic systems do. But we don’t yet know all the microbes behind the modern plagues. Until we understand and identify the key microbes we need to stay heathy, we need to preserve the whole thing.”

To protect as many different kinds of microbes as possible, Dominguez-Bello is training local teams around the world to collect samples from indigenous communities with limited contact with outsiders, whose intestines contain certain kinds of bacteria that may no longer exist in other humans. In her own work in the Venezuelan Amazon rainforest, Dominguez-Bello discovered that the Yanomami—hunter-gatherers subsisting largely on cassava, palm hearts, and wild bananas, as well as fish, frogs, and monkeys—appear to have twice the microbial diversity as people living in the United States.

The new microbe samples will be retained in an international network of regional collections and in a proposed Microbiota Vault—a centralized global repository to be constructed in a safe, cold, politically neutral location. Some call it a Noah’s Ark for beneficial germs.

“We owe future generations the microbes that colonized our ancestors for at least 200,000 years of human evolution,” Dominguez-Bello says. “We must begin before it is too late, for the future of humanity.”

The loss of microbial diversity impacts not only human health but also the well-being of plants, animals, and ecosystems. For instance, healthy soil microbiota are critical for growing food crops and sustaining wildlife, and microbiota in the oceans and other bodies of water that help feed and support the life of countless species are diminishing due to climate change and urbanization.

Such is the case for the relationship between reef-building corals and their microbiome, where nutritional and biogeochemical recycling provides the necessary benefits to fuel high reef productivity. Climate change is taxing the capacity of coral reefs to adapt and maintain ecosystem function under increasing temperatures and ocean acidification. Rutgers researchers are tracking the dynamics of the coral microbiome across stressors, treatments, and time.

Without microbial diversity, biodiversity of all kinds suffers—and the planet is less able to support the panoply of life.

Restoring health

One goal of the Microbiome Project is to develop interventions that can reseed and restore beneficial microbes in the digestive tracts of people whose health is at risk because of diminished microbial diversity, which often results from poor diet and/or antibiotic overuse.

“Restoring a healthy gut microbiome is key to helping patients recover their health and regain quality of life,” Zhao says. A highly processed, low-fiber diet (which is common in the U.S.) does not adequately feed our microbiota and is one of many microbial changes people who move from traditional societies to urbanized ones experience, causing rates of numerous chronic illnesses to skyrocket. People following typical modern eating patterns who reduce their microbe diversity may need to adjust their diet or use nutritional products that support the beneficial bacteria in their bodies.

“Our ancestors took in 200 to 400 grams of dietary fiber a day; we now take in 20 grams or even less,” says Zhao, the lead author of a groundbreaking 2018 study in Science that found a high-fiber diet that included whole grains, traditional Chinese medicinal foods, and prebiotics positively altered the microbiota in subjects with type 2 diabetes, improving  disease outcomes. “Back when Chinese students came to the United States in the 1980s, many of them started to develop type 2 diabetes, which is rare among their siblings who remained in China.”

Working with private industry, Rutgers scientists are at the vanguard of an international effort to link microbial diversity with health and disease outcomes. These partnerships also aim to produce, deliver, grow, and engineer food and supplements designed to meet the microbiota needs of people of diverse ethnicities, cultures, and geographic origins. New Jersey ranks fourth in the United States for diversity, making Rutgers an ideal place from which to launch these research endeavors and translate them into life-changing therapeutics that meet the needs of our diverse communities. With access to over 4 million patients through Rutgers Health and our partner RWJBarnabas Health, the largest health system in New Jersey, Rutgers has a unique opportunity to apply scientific discoveries to bedside treatments and vice versa—taking real‐time clinical observations into the laboratory for further exploration.

In partnership with DuPont Nutrition & Biosciences, Blaser has begun a two-year study focused on improving quality of life in cancer patients by modulating the microbiome to decrease gut inflammation caused by chemotherapy. Recent studies demonstrate that the microbiome plays an important role in gut inflammation and that oral intake of oncology drugs can induce enterocolitis, or inflammation of the digestive tract. The administration of beneficial microbes and supplements may lead to improved overall patient care and comfort for people undergoing cancer treatment.

“The interaction of the microbiome with cancer is an important frontier. Our project aims to discover new ways to improve cancer therapies,” says Blaser.

Impact of the pandemic

The COVID-19 pandemic has not derailed Rutgers’ microbiome scientists. Recently, Dominguez-Bello turned to Zoom to train teams in Peru on the microbe collection process, altering the original plan to conduct these workshops in person. “And that’s okay,” she says, adding that the next locations for trainings are Indonesia and Guatemala.

For Zhao, the pandemic prompted a new study focused on people with diabetes who are diagnosed with COVID-19. “Their gut is overgrown with various pathogens and therefore their foundation guild [the healthy microbiota that work together in the gut] is low, so they have a much higher risk of bacterial complications,” Zhao says. In partnership with the University of South Florida, Zhao is evaluating whether a nutritional supplement aimed at bolstering coronavirus patients’ foundation guild early in the course of the illness can reduce disease severity and/or the need for hospitalization.

Meanwhile, Blaser is studying the potential connection between the microbiome and COVID-19 with funding from Danone North America. “Our hypothesis is that the health of the microbiome prior to COVID-19 infection is a predictor of the severity of COVID-19 and susceptibility for long-haul symptoms,” Blaser says. “The key is to study people before they got infected to determine the possibility of harnessing beneficial microbes to develop new pre- and probiotics. We hope this leads to COVID-19 management strategies, including treatment and prevention through dietary intervention.”

Rutgers at the forefront

As microbiome science expands, academic centers must position themselves to fulfill the multidisciplinary requirements needed to fully understand the role of microbiota and their dynamic interactions with their hosts and other microbes. It is also critical to develop capacities to engineer new diagnostics and develop interventional strategies that can be applied in a variety of fields, including ecology, agriculture, nutrition, and medicine.

Already, the Microbiome Program has mobilized more than 100 innovative and intellectually diverse scientists and physicians representing multiple disciplines, including genetics, metabolomics, proteomics, pharmacy, computer science, engineering, medicine, chemistry, biology, and nutrition. The team benefits from Rutgers’ unique and robust resources, which include the Center for Advanced Biotechnology and Medicine; the New Jersey Institute for Food, Nutrition, and Health; the Rutgers University Cell and DNA Repository; the Office of Research and Economic Development; the NIH-funded CTSA (NJActs); and the Rutgers University Biomedical Research Innovation Cores, which offer a variety of analytical tools to assist with all aspects of microbiome research.

As the nation’s eighth oldest academic institution and a public land-grant university, Rutgers is committed to teaching the next generation of innovators and sharing science-based knowledge with the public. Given the promising impact of microbiome research, it is fitting that the university is supporting cutting-edge microbiome research with the input of bioethicists, social scientists, economists, and attorneys working at the intersections of science, technology, bioinformatics, politics, and public health to generate a deeper understanding and provide clearer communication to policy makers, economists, and the public.

All of these assets position Rutgers to establish a high-impact microbiome program—truly a first of its kind globally.

“We cannot use the traditional way of doing research to understand the microbiome,” says Zhao. “But if we work together, we can achieve great things.”