NIH announces T-R01 project award to examine human microbiome

The National Institutes of Health (NIH) announced today that Martin J. Blaser, MD, the Frederick H. King Professor of Internal Medicine at NYU Langone Medical Center has been awarded one of only twenty NIH Director's Transformative Research Projects (T-R01) award for research entitled "Disappearing Gastrointestinal Microbiota in Epidemic Obesity. The project will examine whether changes in the human microbiome as a result of antibiotic use early in life has fueled the epidemic of obesity. The amount of the award is approximately $6.6 million over a five year period.

"We are deeply committed to the mandate of translational research and will use the opportunity to try to prevent and treat obesity which has become a global epidemic," says Vivian S. Lee, MD, PhD, MBA, senior vice president, vice dean for science and chief scientific officer at NYU Langone Medical Center. "We are excited that collaborations between multiple departments at the medical center may result in research that could be transformative and far-reaching."

Currently, over 1/3 of U.S. adults are obese and one of six children are overweight. In fact, rates of obesity have increased so rapidly over the past three decades that scientists believe that there must be an environmental cause. Dr. Blaser and colleagues hypothesize that antibiotic use early in life has resulted in the disappearance, or extinction, of key microbiota in the human gastrointestinal tract.

Antibiotic use in children may have resulted in the gradual disappearance of Helicobacter pylori, the ancient stomach bacteria that interact with hormones, to maintain energy homeostasis. Dr. Blaser has also observed that use of low dose antibiotics in farm animals to promote growth may also have had a parallel result in human children repeatedly exposed to high-dose antibiotic doses at a very young age. He hypothesizes that antibiotic use could be disrupting metabolic relationships that control early life development.

"The human microbiome has been selected, and passed from mother to child, because the bacterial genes are helpful," says Dr. Blaser who is also a professor of Microbiology at NYU Langone Medical Center. "But as a result of modern practices including widespread antibiotics use, caesarean sections, amalgam dental fillings, constant cleansing, clean water, smaller families and transmission of these normal ancestral microbes has changed, and there are consequences. Some consequences might be good, while others could be bad."

Dr. Blaser and his colleagues at NYU Langone Medical Center have been studying microbes for over thirty years. Microbal cells, collectively known as the human microbiome, reside on our skin and inside our bodies, outnumbering the cells of our own bodies by 10 to 1. They communicate with our own cells and with our immune system, carry out essential metabolic tasks, crowd out pathogens, degrade toxins, and help digest our food.

Advances in DNA sequencing technologies have allowed for further investigation of microbes. Through the Human Microbiome Project (HMP), over 900 species of microbes have been genetically sequenced in an effort to determine the ways changes in the microbiome correlate with human health and disease. The T-R01 grant will help further the understanding of metabolic effects of antibiotic use on normal microbiome development.

"Right now, antibiotics are used in children early in life to treat ear infections and other ailments, and the thought process is that it may not 'help', but it certainly doesn't 'hurt,'" says Dr. Blaser. "But what if antibiotic use actually 'hurts?' What if there are unintended consequences of the 'use' or 'overuse' of antibiotics? This is the question we hope to answer."

The grant will involve multiple departments at NYU Langone Medical Center, including the Departments of Medicine, Pathology Radiology, Obstetrics and Gynecology, Environmental Medicine, and Microbiology and support multiple studies:

•Scientists plan to assess the roles of gastric and colonic microbiota related to hormones and metabolism in both humans and mice. One focus is on the major gastric bacterium, H. pylori, that interacts with gastric mucosal neuroendocrine cells that produce leptin and ghrelin, hormones that are central to energy homeostasis.

•A study will explore the maternal contribution and early development of the colonic microbiota, especially as perturbed by antibiotics, and examine host phenotypes relevant to altered metabolism.

•A study will examine the relationship in children and young adults of H. pylori to their energy homeostasis hormones.

•Another study will involve a cohort in the Netherlands which has already enrolled 10,000 pregnant women and has been following their children for 5-6 years.

•The scientists will examine giving low doses of antibiotics to mice to see whether they gain weight and increase their fat mass, something that has already been documented.

Source : The National Institutes of Health