Baylor Professor’s Cancer Battle Spurs Study of the Microbiome, Diet and Disease

January 23, 2020

Over the last 14 years, the study of the microbiome in humans—the collection of microorganisms found throughout the body in areas such as the gastrointestinal (GI) tract—has become a rapidly growing field, blazing new trails in understanding the relationship between diet, microorganisms and health. Among this discipline’s early practitioners is Baylor professor Leigh Greathouse, Ph.D., whose research focuses on the development of clinical tools to improve the treatment of colon cancer.

Rapid growth in any field calls for ethical leaders at the forefront who identify the practices, standards and discipline needed to shape the best possible research along the way. Greathouse, who joined the Baylor faculty in 2015 as an assistant professor of nutrition sciences in Baylor Family & Consumer Sciences, has done just that. Her recent article in the journal Genome Biology, which argued for consistent DNA extraction methods, is a call for more exacting standards to move the discipline forward and ensure better outcomes for the people the research serves.

For Greathouse, it’s the latest step on a journey motivated by her own experience as a cancer survivor.

“CANCER-FREE”

At just 24 years of age, Greathouse experienced unusual stomach pains which proved to be the symptom of something much deeper—stage IV uterine leiomyosarcoma. That diagnosis led her on a journey through six rounds of chemotherapy and multiple surgeries before finally hearing the words “cancer-free.” Even after overcoming the disease, lingering gastrointestinal issues caused by her surgery forced a continued fight through illness and discomfort. In the midst of that battle, she noticed a correlation that would eventually become a calling.

“I noticed that when I changed from eating ‘comfort food’ to food I knew was healthy and anti-inflammatory, I had a dramatic improvement in my energy,” Greathouse recalls. “This really drove home the importance of diet in response to cancer therapy. Also, my long-term battle with GI issues after my cancer treatment was over really focused my attention on preventing and alleviating GI issues during and after cancer treatment.”

In 2006, the study of the relationship between the diet, gut and disease began to galvanize after technological advances made it easier for researchers to identify microbes for study. Over the next few years, Greathouse would focus on these issues while receiving her Ph.D. from the University of Texas M.D. Anderson Cancer Center, a Masters of Public Health at Johns Hopkins University and serving as a postdoc researcher at the National Cancer Institute in Bethesda, Maryland.

“These early studies really got me excited; they were paradigm-shifting,” Greathouse says. “At a conference, just as I was starting my postdoc, a researcher named Peter Turnbaugh demonstrated that if you transferred fecal samples from an obese human to a mouse with no microbiome, that mouse became obese, independent of diet. A few months later while at a seminar, a physician demonstrated that patients with colon cancer had a distinct gut microbiome that might be useful for early diagnosis. A light bulb went off, and thus started my adventure in the field of microbiome research.”

STRONG STANDARDIZATION

After completing her postdoctoral fellowship at the National Cancer Institute, Greathouse began her work at Baylor. Here, she established the Laboratory of Health and Human Behavior, and continued a research portfolio that includes numerous publications on topics such as the microbiome and cancer, obesity, reproductive health and more. Less than a decade after those pioneering studies launched a new field, Greathouse had a home in which to conduct quality research into microbiome and cancer.

The field’s rapid growth, however, brought incumbent challenges that call for leadership. Exponential growth outpaced standardization, creating a need for universal methods in the field to ensure accuracy and quality, in areas like DNA collection and extraction, sample storage, control and more. Failure to follow through in any one of these areas could taint samples, and therefore, study results—results which could have a real impact on people.

Last fall, she provided that leadership by serving as the lead author of a Genome Biology journal article sounding a call for standardization in processing steps for human microbiome studies. It casts a compelling vision for a field poised to make a positive impact in the years ahead, with five recommendations to set protocols for DNA extraction from a variety of sources and samples:

  • Collect and process negative controls at each of the following points: during sample collection, DNA extraction, and sequencing
  • Include at least one or more of the following three types of positive controls in each experiment, depending on study: a complex environmental sample, chemostat community, or mock community
  • Report in detail the DNA extraction methods followed and sufficient information regarding the results from both positive and negative controls in a manner that allows for peer-review and reproducibility
  • Utilize the same DNA extraction protocol across studies for multi-institute or multi-site studies
  • Demonstrate “proof-of-life” beyond sequencing in low-biomass studies using microbial culture and/or FISH

“Moving forward, I’d like to see really strong standardization among the types of methodology we have in doing microbiome studies,” Greathouse says. “We’re seeing that changes in your gut community affects disease, obesity, mood, behavior, autism, so many things. We’re ready for protocols, that people could find, perhaps online and available for download, where they could find these protocols and follow them, because we know those are standard in the field. That’s one thing we need going forward.”

As the field moves forward— thanks in part to her research— Greathouse trains the next generation of trailblazing microbiome researchers at Baylor. Attracted by Baylor’s Christian environment and commitment to research, Greathouse has found a place teeming with opportunities for interdisciplinary collaboration and mentorship opportunities with students who desire to be at the forefront of a field which could impact every family.

“I wanted to do good science in an environment supportive of my goals,” Greathouse says. “I wanted to be able to mentor young investigators, young scientists, to empower them with the knowledge and ability to recognize good science and bad science and solve problems. Baylor provides such a supportive environment, and together we can find solutions to questions about the gut and health that can truly help consumers.”

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