In terms of diversity and sheer numbers, the microbes occupying the human gut easily dwarf the billions of people inhabiting the Earth.
Numbering in the tens of trillions and representing many thousands of distinct genetic families, this microbiome, as it's called, helps the body perform a variety of regulatory and digestive functions, many still poorly understood.
How this microbial mélange may be linked to body weight changes associated with morbid obesity is a relevant and important clinical question that has received recent attention. Now, a new study suggests that the composition of microbes within the gut may hold a key to one cause of obesity - and the prospect of future treatment.
In the January 19 early online edition of the Proceedings of the National Academy of Science , researchers at Arizona State University's Biodesign Institute in collaboration with colleagues at the Mayo Clinic, Arizona, and the University of Arizona, reveal a tantalizing link between differing microbial populations in the human gut and body weight among three distinct groups: normal weight individuals, those who have undergone gastric bypass surgery, and patients suffering the condition of morbid obesity—a serious, often life-threatening condition associated with diabetes, cardiovascular disease, cancer and psychosocial disorders. Obesity affects around 4 million Americans and, each year, some 300,000 die from obesity-related illness.
A collaboration aimed at uncovering the links between the microbial composition of the human gut and morbid obesity began when Dr. John DiBaise, a gastroenterologist at the Mayo Clinic, Arizona, became interested in both the underlying mechanisms of obesity and plausible alternatives to gastric bypass surgery—still the only reliable long-term treatment for the extremely overweight.
DiBaise turned to Bruce Rittmann, Ph.D., an environmental engineer and a member of National Academy of Engineering, whose Center for Environmental Biotechnology uses its expertise to examine microbial populations important for cleaning up pollutants and generating renewable bioenergy. Rittmann invited Rosa Krajmalnik-Brown, assistant professor of civil and environmental engineering, to collaborate and apply her microbial ecology expertise to this project. The three researchers were able to leverage seed funding from the Mayo Clinic and ASU so that they could combine their respective talents. DiBaise recruited 9 middle-aged volunteers in three groups—normal weight, morbidly obese and following gastric bypass surgery—to participate in the study.
The research team's central hypothesis is that differing microbial populations in the gut allow the body to harvest more energy, making people more susceptible to developing obesity. These small differences can, over time, profoundly affect an individual's weight. Supporting this view is the study's confirmation that the microbial composition among obese patients appears significantly altered compared with both normal weight individuals and those who have undergone gastric bypass surgery.
A microbial managerie
To tease out the microbial human gut composition, Husen Zhang, a postdoctoral scholar working with Rittmann and Krajmalnik-Brown, used an advanced DNA sequencing technology and sophisticated ecological tools. The team examined 184,094 gene sequences of microbial 16S rRNA, a molecular structure which provides a characteristic fingerprint for microbial identification. The analysis was conducted with the assistance of University of Arizona's Rod Wing at the Bio5 Institute, using a novel sequencing technique known as 454-pyrosequencing, which allows a significantly larger number and greater diversity of gut microbia to be identified.
The group's latest findings represent the first investigation of gut microbiota from post-gastric-bypass patients to date.
By examining a specific region of the 16S rRNA gene known as V6—PCR amplified from the stool samples of the 9 test subjects—the researchers were able to classify a zoo of microorganisms, which fell into 6 broad categories, with two bacterial phyla, the bacteroidetes and firmicutes, predominanting.
The resulting composition of gut microbiota in the three gastric bypass patients differed substantially and in potentially important ways from obese and normal weight individuals. This means the drastic anatomical changes created by gastric bypass surgery appear to have profound effects on the microorganisms that inhabit the intestine. This change may be part of the reason that gastric-bypass surgery is the most effective means to treat obesity today.