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First we eat. Then we do everything else.

First we eat. Then we do everything else.

by Elise Wachspress

One of the goals of the Duchossois Family Institute (DFI) is to understand how our own individual genes, those of the microbes cohabiting with us, and the many metabolites they produce all work together to create healthy, robust biological systems—or fail to do so.

Over the past century, medical science has shown great success in creating drugs and other treatments that address human ailments and extend lifetimes. It excels in rescuing people from acute disease and fighting pathogens (like developing multiple vaccines against a new and evolving virus within less than a year). The important challenge before us now—less apparently heroic, but potentially much more powerful—is to reduce vulnerability to chronic diseases, a problem escalating all over the world, even in developing countries.

The DFI was created around a central question: what if we could tune the factors involved in human health to achieve and maintain vigor throughout our lives? If science could help humans become their most robust selves, societies around the world stand to gain in happiness and productivity, rather than just increased longevity.

To achieve this goal depends on a new kind of interdisciplinary science, one that can make sense of the endlessly complex interactions among human gene products, microbial genes and metabolites, the foods we eat, and the chemicals in our environment. To do this most rationally and efficiently, Arjun Raman, MD, PhD, wants to focus on discovering the most basic principles that underlie the structure, function, and adaptability of these relationships.

We have, he believes, a surfeit of data already captured in electronic health records, complex genetics studies, and many more sources. Now we must leverage these data, using computation, theory, and experiment, to unearth the biological “wiring diagram” that will allow us to rationally engineer solutions for human health.

In a recent paper in Science, Raman and colleagues proposed to attack this issue at the level of one critical “food web,” one both simple and complex: the “triad” of mother, newborn, and breastmilk.

We know that breastfeeding supports infant health and development and influences later cognitive ability or risk for conditions like obesity or diabetes. Studies have also suggested that nursing seems to provide lifelong health benefits to the mother, including decreased risk of sex-related cancers and cardiometabolic disorders.

While vast caches of data at the population level demonstrate these correlations, we still don’t really understand exactly how these work. By figuring out the mechanisms involved, we can identify the most critical elements, so moms—and whole societies—can set their children on a path for vigorous good health. This is especially important in cases where babies are born prematurely or in resource-limited environments, when mothers’ bodies are unready or unable to provide the nutrition babies need.

In their paper, Raman and company argue that breastfeeding is a co-adaptive system and breastmilk a “live tissue” with not only macro- and micro-nutrients, but also essential bioactive compounds (like the chemicals that give structure to the fat droplets critical for brain development), micro RNAs, even cells and microbes. In fact, the nutrients in breastmilk may initially be more important in feeding the essential microbes in babies’ guts as they are for the children themselves.

What are the factors most important for the child’s microbial community to thrive and spur robust development? In babies born too early or at an environmental disadvantage, what are the best ways to repair the gut community? How does breast milk change over the nursing arc? How do the interactions between the genomes—mother, child, microbes—and the environment work together—or not—to maximize healthy growth?

Finding the answers to these questions can help us figure out how to save the lives of babies at risk. But Raman is looking for much more. By figuring out the basic principles that guide these factors and how they relate to each other in the earliest days of life, perhaps science can develop theoretical constructs that can accelerate breakthroughs, much like the theory of gravity or the periodic table or Darwinian evolution have provided powerful “shortcuts” to discovery in physics or chemistry or biology.

Raman was attracted to come back to UChicago—where he earned two undergraduate degrees—after years of study in medicine, clinical pathology, and molecular biophysics, at Washington University and University of Texas Southwestern, because he believed the resources at the DFI, with access to great expertise in computation, microbiology, genetics, and diverse clinical populations, is the perfect place to start generating useful theory.

One day, he believes, we will be able to develop health strategies and risk stratification for individuals in a data-driven way. Perhaps we’ll be able to use inflammatory markers to help create a “tuning device” for health, with personalized combinations of foods providing the “push” to adapt and repair the gut microbiome of people at genetic and environmental risk for disease.

Raman’s work has already helped colleagues have made inroads in this effort for malnourished children in Bangladesh. It’s an effort that could help completely change the way we think about medicine. And elevate opportunities for vigor in people everywhere.

Elise Wachspress is a senior communications strategist for the University of Chicago Medicine & Biological Sciences Development office