the microbiome -- 7/21/14

Today's selection -- from "Microbiomics: The Next Big Thing?" by Lisa J. Bain. It is estimated that we each have 10 trillion of our own cells, accompanied by an even greater 100 trillion "good" bacterial cells. These bacterial cells, along with assorted viruses, fungi and other microbes, collectively constitute what is often referred to as the microbiome. Researchers now believe the microbiome is essential for the proper functioning of the body -- and that antibiotics often deplete the microbiome, impairing body function and causing maladies:

"Although it may sound weird, unappealing, even disgusting, fecal transplantation has piqued the interest of gastroenterologists and infectious disease specialists around the world. Meanwhile, patients suffering from severe diarrhea are demanding the procedure and the FDA has weighed in with restrictions on how this 'unapproved therapy' can be delivered.

"Why all the excitement? Fecal transplantation is not new: Ben Eiseman, a surgeon at the University of Colorado, described it more than 50 years ago to treat a life-threatening diarrheal disease caused by a bacterium called pseudomonas enterocolitis. But until a few years ago, Eiseman's unconventional treatment was largely dismissed by the medical community, at least in the United States (it has been much more widely used in Australia). Then, in 2010, The New York Times ran a story about a doctor in Minnesota using fecal transplantation to successfully treat a patient with a severe infection caused by a bacterium called Clostridium difficile, or 'C. diff.' And this year, a randomized controlled trial of the treatment was stopped early when an interim review of the data showed not only that it worked, but that it was far superior to the standard treatment with powerful antibiotics. Fecal transplantation, also known as fecal microbiota transplantation (FMT) or bacteriotherapy, had arrived.

Spores of Clostridium difficile

"The acceptance of FMT for the treatment of diarrheal disease caused by C. diff exemplifies a paradigm shift in how many diseases are viewed, as well as a translational application of the science of microbiomics -- a rapidly expanding research field that Science magazine dubbed 'The Germ Theory of Everything.' Microbiomics researchers have shown that the human body is home to an entire ecosystem of bacteria, viruses, fungi, and other microbes, and that these bugs play important roles in keeping us healthy and regulating all sorts of physiologic processes. When the gut microbiota (the population of microbes) is disrupted, for example by overuse of antibiotics, the consequences can be lethal, as is the case with C. diff. It infects as many as 3 million people worldwide each year and in recent years these infections have become less and less responsive to antibiotic treatment. In the U.S. alone, medical costs to treat C. diff infections exceed $1 billion per year, and some 14,000 Americans die from the infections.

"Following on the heels of the massive Human Genome Project, which identified about 22,000 protein-coding genes in humans, the National Institutes of Health launched the Human Microbiome Project (HMP) in 2007 to map the collective genomes of the human microbiota. HMP researchers at nearly 80 institutions, including [the University of Pennsylvania], analyzed tissue from 242 healthy individuals, sampling 15 body sites in men and 18 in women. The findings made the genome project look modest in comparison: the human gut microbiome alone is home to 100 trillion bacteria -- ten times the number of cells in the human body -- with somewhere around 8 million protein-coding genes, 360 times as many as in the human genome.

"The same gene sequencing technology that fueled the genome project also made mapping the microbiome possible. 'You literally can get more than a hundred billion bases of sequence information from a single instrument run these days,' says Frederic Bushman, Ph.D., professor of microbiology. 'It's astounding. We're analyzing a dataset of over a trillion bases of sequence information. When I was a student, it would be a few days' work to get a few reads of a hundred bases each. Today, I have a little machine in my lab that will do a hundred thousand sequence reads of about 250 bases each in a day.' One of the changes the new technology has brought about in Bushman's research is the makeup of his laboratory personnel: 'We now have four programmers in the lab and lots of collaborating statisticians to work with that kind of data. That's all new in the last ten years.'

"Indeed, gene sequencing has brought about a transformation in the entire field of microbiology, as it has in many other areas of biomedical research. David Artis, Ph.D., associate professor of microbiology, says that when he completed his training in immunology back in the mid-'90s, he was advised not to be concerned about the microbiota or what was then referred to as the commensal bacteria (bacteria that live harmoniously with the host) that colonized the intestine. 'We were told, "don't worry about it -- it's too complicated, you can't culture the bugs, and you can't phenotype what they are." What has been an incredible journey for us has been the rapidity with which we've been able to engage and interrogate the role of the microbiome in the last decade or so.' "


Lisa J. Bain


"Microbiomics: The Next Big Thing?"


PENN Medicine


Spring 2014


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