Science Life - A blog of news and ideas in Biomedicine

A Top-Down Approach to Treating Crohn’s Disease

Posted at 10:30 am CT on April 16, 2012

topdownBy Matt Wood

Crohn’s disease is a form of inflammatory bowel disease that can cause painful abdominal cramps, diarrhea, fever, fatigue, loss of appetite and weight loss. These symptoms can lead to poor quality of life and cause significant stress, as people with Crohn’s limit their activities for fear of flare-ups and having an accident in public.

There is no known cure for Crohn’s disease, and treatment involves a “step up” strategy that start with first-line medications to manage symptoms. But a gastroenterologist at the University of Chicago Medicine has taken a closer look at a “top down” approach that reverses the conventional order of treatment by starting with biologic therapies.

Traditional treatment for Crohn’s patients is focused on a strategy of managing inflammatory symptoms, starting with simpler and less costly oral medications such as aminosalicylates (5-ASAs) and corticosteroids, and escalating through a series of steps to more expensive biological therapies that target specific proteins in the immune system’s inflammatory response. David Rubin, MD, associate professor of medicine, co-director of the University of Chicago Medicine’s Inflammatory Bowel Disease Center, studied the newer top-down strategy that reverses this order of treatment. He found that patients treated with biologic therapies earlier were significantly less likely to need steroids, lose response to their biologic therapy, and require surgery related to their Crohn’s disease.

“We’re essentially reversing the management strategy in Crohn’s disease,” said Rubin. He emphasized that the medications often used first for patients with Crohn’s are also the least effective and carry risks for side effects. “We’ve long discussed and debated that 5-ASAs don’t work in the majority of Crohn’s patients, and certainly don’t change any outcomes,” he said. “Steroids are ineffective long-term and are also dangerous because they have significant side effects such as infections.”

Crohn’s is a disorder in which the body’s immune system appears to have lost the ability to regulate itself and becomes overactive, causing progressive damage to the bowel structure and function.  Patients often need bowel surgery to repair this damage. Researchers have made great progress finding genetic and environmental contributors to Crohn’s disease, but the actual cause is unknown.

Rubin said that physicians have questioned the effectiveness of the step-up strategy because patients experience little relief while being treated with medications before they receive the biological therapies. During that time, they suffer from active disease, have low rates of remission and often appear to lose response to the biological therapies.

In recent years a treatment strategy that starts with the targeted biologic therapy as a first option has been explored in controlled clinical trials. The results were encouraging, and suggested that such an approach results in higher remission rates. However, it was not clear whether this top-down approach would translate to the general population of patients with Crohn’s disease, or whether such an approach would maintain the response to biologic therapy and decrease the need for surgery.

The FDA approved the first targeted biologic therapy for Crohn’s disease in 1998 and the second two in 2007 and 2008. Rubin said that because they are expensive, must be administered through injections instead of pills and are typically saved until last, physicians are hesitant to prescribe them earlier. “Patients and doctors are nervous about immune suppressive therapies. The perception in the current treatment algorithm is that the therapies saved for last must also be the most dangerous,” he said.  “But that’s the wrong thinking, and by delaying their prescription it may be a self-fulfilling prophecy because by then patients have suffered more damage to their bowels and are less likely to respond favorably.”

In the study, published in the journal Inflammatory Bowel Diseases, Rubin and his colleagues analyzed health insurance claims from a database that includes records from more than 94 commercial health plans throughout the United States. Patients eligible for the study had to be enrolled in the same health plan continuously for at least six months before the first claim related to Crohn’s, and stay enrolled for at least 12 months after the first claim for anti-TNF treatments.

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Posted by - Matt Wood

Food Allergies vs. Food Intolerance

Posted at 8:57 am CT on March 23, 2012

1024px-allergy_foodBy Matt Wood

Adverse reactions to foods, including eggs, milk, peanuts, tree nuts, wheat, shellfish and soy, are on the rise, especially among children. The CDC reports (PDF) that between 1997 and 2007, food allergies increased 18 percent in children under the age of 18. While we generally categorize all adverse reactions as “allergies,” they actually cover a range of immune system responses and disorders of the digestive system, each with its own causes and varying levels of severity.

In a paper published in Current Gastroenterology Reports, Stefano Guandalini, MD, section chief of pediatric gastroenterology, hepatology and nutrition at the University of Chicago Medicine, and Catherine Newland, a pediatric gastroenterology fellow, reviewed the major forms of food allergies and intolerances to help navigate this confusion and provide a guide for treatment and prevention options.

While bad reactions to food are extremely common, only a few can be defined as allergic reactions. An allergic reaction is caused by an immune system response to a specific allergen present in food, such as the proteins in cow’s milk or soybeans. If a person with a food allergy is exposed to these proteins, their body flags them with Immunoglobulin E (IgE) antibodies, which normally help fight parasites. The body’s immune system then mistakenly thinks these proteins are harmful and triggers an allergic reaction, such as skin rash, gastrointestinal or respiratory distress and the more life-threatening anaphylactic shock. An example of another type of immune reaction, not mediated by IgE, is celiac disease. Celiac is an autoimmune condition in which the body responds to the wheat protein gluten by destroying its own villi that absorb nutrients in the small intestine.

Food intolerance, on the other hand, is a broader term encompassing all adverse food reactions. “A food sensitivity or intolerance is a more generic term, comprehensive of any adverse food reaction, that can be immune-mediated but also may not be immune-mediated,” Guandalini said. “For instance, some people react to the tyramine present in cheeses. This is due to release of histamine, and is not an immune process.” Lactose intolerance is another common problem caused by the inability of the body to digest lactose, a sugar present in milk. Unfortunately, this distinction makes little difference to someone suffering from any kind of food intolerance because the symptoms are often similar.

The reason for the increased prevalence of food allergies and intolerances is unclear, but Guandalini says a leading theory is the “hygiene hypothesis.” Lack of early childhood exposure to infectious diseases, microorganisms and parasites as a result of industrialization, clean drinking water and modern medicine may be suppressing natural development of the immune system and increasing our susceptibility to allergies. Cathryn Nagler, Ph.D., a food allergy professor at the University of Chicago, is also studying how modern lifestyles, including high-fat diets, antibiotics and the use of baby formula instead of breastfeeding are changing the bacteria that live inside our bodies to produce more sensitivity to certain foods.

Tactics to prevent food intolerances from developing in children, - such as mothers restricting their diets during pregnancy, then breastfeeding and waiting to introduce certain foods to baby’s diet - have mixed results. If allergies do develop, Guandalini says that desensitization, or controlled exposure to allergens, shows promise for helping people tolerate problem foods such as milk or peanuts, but it requires more research. Until then, the only option is avoidance, one that many people with a food intolerance figure out the hard way on their own.

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Guandalini, S., & Newland, C. (2011). Differentiating Food Allergies from Food Intolerances Current Gastroenterology Reports, 13 (5), 426-434 DOI: 10.1007/s11894-011-0215-7

Posted by - Matt Wood

When Computer Infections Help Science

Posted at 10:24 am CT on March 7, 2012

500px-cpt-internet-skullncrossbonessvgUnder normal circumstances, people want to keep infections away from their computers. But for Gary An, reconstructing nasty infections inside a computer is a research project, not an act of cyber-terrorism. In collaboration with laboratories at the University of Chicago Medicine studying infectious diseases, An is creating computer models that simulate the delicate, complex balance between bacteria and their home in the human gut. By replicating the results of previous experiments within computational space, An hopes to enable in silico experiments that can push scientific discovery beyond the confines of the lab bench.

In two recent papers, An, associate professor of surgery at the University of Chicago Medicine, describes computer models that simulate a common post-surgical infection and a rare but very serious gastrointestinal condition that strikes premature infants. In both cases, the model uses research findings to recreate at least a portion of the microbe-host relationship in the gut, in order to look for clues as to why bacteria that normally live peacefully inside the intestines suddenly decide to attack.

Pseudomonas aeruginosa, a common cause of infection in patients recovering from surgery, is one such tenant turned aggressor. Most people are colonized by P. aeruginosa without ever realizing it, as it finds a quiet home in the lining of the gut alongside thousands of other bacterial species. That’s until the human host grows ill or undergoes major surgery and the comfort of the gut is disrupted, sometimes causing P. aeruginosa to riot. But this breakdown of what John Alverdy, professor of surgery, calls “molecular diplomacy” doesn’t always occur, creating a need for models that can describe how this system works — and fails.

“Part of the point of studying this particular bacterium and its role in infection is that there is a dynamic interplay between the bacterium itself and its environment…which happens to be a human,” An said. “The idea is to use the modeling as an iterative tool to help basic science labs do what they do a bit more efficiently. Using this model, we can gain insight into what they need to work on in the future.”

Surgical fellow John Seal led the effort to create a computer simulation of P. aeruginosa in the gut using agent-based modeling, where the simple actions of individual bacteria or cells sum up to a dynamic, complex system. In this case the “agents” are the bacterial and epithelial cells, which are set in Seal’s model against a backdrop of the gut’s mucosal layer and intestinal lumen. How those agents interact, and what various changes in the environment do to their behavior, were modeled after the results of experiments conducted over many years in Alverdy’s laboratory. As the model grew, the designers frequently tested it back against those experiments, to make sure the results of running the model accurately replicated what has been observed in the lab.

“It’s actually a very rigorous sort of thing, since we’re making it all up,” An said. “There are no laws of physics or chemistry in the model. It will do whatever you make it do. It’s potentially dangerous to get off track easily, therefore you constantly need to have reality checks back to the behavior of the system.”

Now that the system is in place, the science can move into the in silico world. Researchers can challenge the system in ways that would be difficult to do in a lab dish or an animal model, and can receive feedback on how the bacteria will respond. In the 2011 paper, published in Theoretical Biology and Medical Modeling, the team simulated conditions of host stress by adding inflammatory factors or endogenous opioids to the model to observe how they affect the virulence of P. aeruginosa — the likelihood that it will break its truce with the surrounding gut and attack. These simulations can generate new hypotheses to test in the laboratory, and also clue researchers into how best to run those experiments, such as suggesting the best timepoints to sample in a real-world experiment.

In another model, the same principles are applied to a disease called necrotizing enterocolitis, or NEC. Seen most often in babies born prematurely, the disease causes severe inflammation of the intestines that must be treated with severe surgery to avoid mortality. But despite clues gathered from animal experiments about the importance of early diet, feeding tubes, and the makeup of the gut’s bacterial ecosystem, no full model exists to predict which babies are at risk for this disease. An NEC computer model, built by An with fellow Moses Kim and professor of surgery and pediatrics Donald Liu and published in Surgical Infections, could help identify factors that put a premature infant at risk.

“It can’t be every kid that’s born early, can’t be every kid that you feed by tube, can’t be every kid that swallows some bugs. It has to have some particular component associated with that,” An said. “If, for instance, you could find a gene or an expression level in a premature infant that would suggest that their metabolic stress management capability is decreased, then you could identify a sub-population of kids that were at risk beyond the 3 in 1,000 incidence that it currently is at.”

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Posted by - Rob Mitchum

Year in Review: UChicago Research 2011

Posted at 9:00 am CT on December 27, 2011

keenan-fig6_final-small

As another year comes to a close we’d like to look back at the fascinating research breakthroughs and inspiring patient stories from 2011. ScienceLife ran 168 posts this year, and while we wish we could highlight all of them, here are a handful of our favorites from each month.

January

influenza_virusPatrick Wilson found out that the H1N1 virus could end up helping us fight all types of flu. Stephen Pruett-Jones studied how some male birds mimic the sounds of predators to pick up the ladies (with an audio clip). We interviewed David Gozal about his study on the link between childhood obesity and lack of sleep, and took a look at NCAA regulations mandating sickle cell testing for athletes.

February

Harold Pollack gave a lecture on why violent crime in urban, minority communities should be considered a public health epidemic. Siri Atma Greeley studied the actual medical benefit of widespread genetic testing. Stacy Lindau wanted to know why so few women get help for sexual problems after surviving cancer. We talked to Bana Jabri about the causes of celiac disease, and Sliman Bensmaïa showed us how the brain processes the basic elements of touch very much like it handles visual information.

March

Sola Olopade educated women in Nigeria about using clean-burning stoves to prevent indoor pollution. Stefano Allesina and Jonathan Levine looked at how rock-paper-scissors helps explain evolution. Joshua Miller went to Yellowstone Park to see what stories the ghostly bones of animals can tell, and Scott Eggener questioned the wisdom of indiscriminate prostate cancer screening.

Photo by Gerald Waddell

Photo by Gerald Waddell

April

Andrea King studied the wide range of responses to drinking alcohol, and why it can be fun for some people and a bummer for others. Cheryl Reed took a ride in a helicopter with our UCAN nurses. Kamal Sharma looked at the genes that control animals’ gait, and Ningqi Hou studied how urban environments can dictate how much exercise people get.

May

Daniel McGehee looked at the long-term effects of nicotine on the brain. Habibul Ahsan went to Bangladesh to study the health impacts of accidental exposure to arsenic in drinking water. The brain’s overlooked supporting cells got their due at a conference on neuroscience, and we remembered a landmark discovery about a once popular drug taken during pregnancy that we now know can cause cancer.

June

As we headed into summer, Diana Lauderdale used Google to track MRSA. We learned about an extraordinary transplant where a man received a new heart, liver AND kidney. Daniel Geynisman gave us the rundown on whether or not cell phones are killing us (they’re not, as long as you don’t use them in the car), and some UChicago undergrads studied what happens to gorillas on the birth control pill.

limb-switch-graphic-299x3001July

We spoke to Donald Jensen and Andrew Aronsohn about the new outlook for patients with hepatitis C. Igor Schneider made a time machine to find the genetic switch for limb development. Farr Curlin led a study about the benefits of addressing spiritual needs alongside medical care, and Adam Cifu looked at the phenomenon of scientific study reversals.

August

Stefano Allesina dug into the long, shady history of nepotism in academia in Italy. John Schneider talked about his work addressing sexual health and stigma in India. Michael Becker discovered a new treatment for the Royal Disease, and we had the rare chance to name check a Spiderman villain in a post.

September

Martha McClintock and Suzanne Conzen studied the connection between social isolation, stress and breast cancer. Gallego Romero traveled to India to search for the origins of lactose intolerance. Stephanie Dulawa developed a mouse model for OCD, and Paul Vezina looked at a different kind of obsession, compulsive gambling.

October

Arshiya Baig started a pilot project to help people learn about life with diabetes through pictures. Manyuan Long found that some of the youngest genes are in the brain. Jens Ludwig and Stacy Lindau published a landmark study about the connection between neighborhood poverty and health, and Issam Awad studied a rare brain disease that soon could be treated with a drug instead of surgery.

rat-empathy3November

Cathy Pfister and Tim Wootton figured out how to use seashells to track climate change over the years. Lianne Kurina found a link between loneliness and sleep quality. Shantanu Nundy, Monica Peek and Marshall Chin developed a program to send text message reminders to people with diabetes, and Pan Chen looked at the links between childhood abuse and aggressive behavior in adults.

December

Inbal Ben-Ami Bartal, Jean Decety and Peggy Mason discovered that rats can show empathy for their fellow rats in distress. Maciej Lesniak performed a scary but amazing brain surgery on a patient who was awake. Cathryn Nagler searched for the source of food allergies within our bodies, while Stafano Guandalini uncovered the challenges in educating doctors about one of those allergies, celiac disease.

Whew. Hope you were able to click through at least a few of those. We look forward to another great year of research in 2012. We’re taking a break next week, but we’ll be back on January 5. Happy holidays!

Posted by - Matt Wood

Turning the Page on Celiac Education

Posted at 12:28 pm CT on December 7, 2011

BooksBy Matt Wood

Celiac disease, an auto-immune disorder that prevents the digestion of gluten in the small intestine and inhibits absorption of nutrients, is gaining awareness in the United States. Gluten-free options are popping up on restaurant menus, television stars such as Elisabeth Hasselbeck and Jennifer Esposito are going public with their diagnoses, and major food companies including General Mills are developing more gluten-free products and market directly to the celiac community.

A 2003 study estimated that 1 in 133 people in the United States have celiac disease. That means at least 3 million people in this country are living with celiac, but screening studies show that identification of patients lags behind the actual prevalence of the disease. Up to 97 percent of those cases are undiagnosed.

Concerned that a lack of physician awareness of celiac could be contributing to a delay of up to 11 years in the diagnosis of adults in North America, Stefano Guandalini, MD, Medical Director of the University of Chicago Celiac Disease Center, co-authored a study that looks at how well gastroenterologists adhere to established diagnostic and treatment guidelines for celiac disease.

Guandalini and his colleagues at the Celiac Disease Center and the NorthShore University Health System conducted a survey of gastroenterologists who attended the annual Digestive Disease Week conference in 2009. A total of 169 doctors answered questions about vignettes that described cases of possible celiac disease. Guandalini’s team compared the responses to those of 22 experts on celiac disease, and found that very few of the non-expert physicians were able to follow correct diagnostic approaches. “This is a bit alarming because if you think of it, the people who were there were already screened in a way because they are those who actually want to attend a national meeting, so they are seeking an education,” Guandalini said. “Not only that, but they received this paper requesting to participate in this survey, so it means that they already thought themselves to be familiar with celiac disease.”

Until very recently, Guandalini said, basic medical education didn’t teach that celiac disease was widespread in the United States. “Nobody really was ready to accept the 1 percent prevalence of celiac disease,” he told the New York Times recently. In that article he pointed out the example of a medical textbook that put the prevalence of celiac in the United States at 1 in 10,000 as recently as 1999. And when doctors did have any familiarity with celiac, it was with the “classical presentation” of a small child with chronic digestive problems, instead of the myriad symptoms in both children and adults that can lead to a celiac diagnosis, from muscle cramps to an itchy skin rash, especially around the elbows.

As one of the country’s leading authorities, the Celiac Disease Center is doing its part to close this gap in medical education. It recently hosted its sixth annual Preceptorship Program, an on-site, intensive two-day training course for medical professionals who want to learn about diagnosing and treating celiac disease. This year more than 30 doctors, nurses and dieticians attended seminars, got hands-on training and sampled gluten-free foods. While the center offers a comprehensive approach to caring for patients and research toward finding a cure, Guandalini says that medical education is a primary goal. As demonstrated by this latest study, he said, “Clearly there is a lot of education that needs to be done.”

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Parakkal D, Du H, Semer R, Ehrenpreis ED, & Guandalini S (2011). Do Gastroenterologists Adhere to Diagnostic and Treatment Guidelines for Celiac Disease? Journal of clinical gastroenterology PMID: 21959324

Posted by - Matt Wood

The Gut’s Tenants and Food Allergies

Posted at 11:44 am CT on December 2, 2011

nut_warning_1If you are an avid reader of food packaging materials or a parent of an elementary school student, you might get the feeling that food allergies are on the rise. Statistics back up this notion, with the CDC reporting an 18 percent increase [pdf] in child food allergies between 1997 or 2007. That puts current estimates of food allergy prevalence at 4 percent for children and 2 percent for adults, with allergies to peanuts (3.3 million Americans) and shellfish (6.9 million) leading the way.

The factors driving this surge remain a scientific mystery, and answers are even more scarce when it comes to treating or preventing dangerous allergic reactions. Currently, the only way to prevent anaphylaxis caused by a food allergy is avoidance, a strategy that can be very cumbersome for parents raising small children who cannot be exposed to basic food groups. Dave and Denise Bunning faced this challenge with their two children, both of whom were allergic to milk and eggs, leading to “several emergency room visits before the age of 5,” Dave Bunning said. Those experiences inspired the family’s philanthropy for research into the science of food allergies, which included this year’s founding of the Bunning Food Allergy Professorship at the University of Chicago Medical Center.

At the official naming ceremony for the new position, the inaugural Bunning Food Allergy Professor Cathryn Nagler presented her latest research to a large crowd including the Bunning family themselves. Nagler’s intriguing theory about food allergies looks within, at the bacterial universes that exist inside the human body. In parallel with other laboratories on campus looking at the impact of the human “microbiome” upon diseases such as inflammatory bowel disease and diabetes, Nagler is focused on the trillions of bacterial tenants that occupy each of our bodies.

“It’s becoming clear that we are outnumbered,” Nagler said. “There are 10 trillion human cells encoding 20,000 genes [in an individual], but 100 trillion bacterial cells encoding an estimated 2 to 20 million genes. So there are as many E. coli in each of our digestive tracts as there are people on Earth…and that’s not even one of the more popular species.”

All those bacteria, sometimes called the “commensal microbiota” to distinguish them from disease-causing pathogens, could play the environment role in the genes + environment recipe for food allergies. Many of the trappings of modern life, including high-fat diets, antibiotic treatments, and the use of baby formula instead of breastfeeding, can affect the census of our bacterial inhabitants. In food allergies, where the immune system mistakenly treats innocuous dietary proteins as harmful invaders, these microbiota changes might tip the balance towards over-sensitivity to components of peanuts or shrimp.

“An increase in disease prevalence in 10 to 15 years’ time can’t be explained by genetics, so there’s got to be other factors that are driving this increase in disease prevalence,” Nagler said. “All of these environmental variables lead to alterations of the commensal microbiota, which in genetically susceptible individuals could drive allergic responses to food and other antigens.”

To study this model, Nagler’s laboratory gave a long-term treatment of antibiotics to lab mice, finding that this prolonged exposure did indeed trigger an allergic response to peanuts. Using genetic identification methods, her group compared the gut microbiomes of mice treated with antibiotics versus mice who did not receive the drugs, finding several differences in the bacterial populations colonizing their digestive system. One bacterial family, called Clostridia, were reduced in the mice treated with antibiotics, while another was increased — suggesting that reducing or decreasing different species of bacteria might affect the chances of developing food allergy.

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Posted by - Rob Mitchum

The Tools of the Human Microbiome

Posted at 10:32 am CT on July 7, 2011

gut-microbiomeThe latest cult favorite in the sphere of human genetics is the microbiome, the genes of the bacterial species that live inside and upon the human body. Because bacterial cells outnumber human cells in an adult by approximately ten to one, and tens of thousands of different species make up the human ecosystem, studying this world will be even more of a challenge than the Human Genome Project, which only had to concern itself with a single species: us. But as the microbiome is increasingly discovered to play a role in obesity, diabetes, infant diseases, and hospital-acquired infections, the number of researchers pondering a bacterial angle for their own disease of interest is exploding.

So the microbiome was the ideal topic for the first lecture of the Institute for Translational Medicine seminar series on Advanced Tools, a monthly meeting designed for University of Chicago researchers to share methodological know-how. Leading the discussion was a veteran of the young microbiome scene - Eugene Chang, professor of medicine and an expert on gastroenterology. For several years, Chang has applied the tools of microbiology to the bacterial populations of the human gut, looking for mechanisms involved in digestive diseases. As the techniques for studying the microbiome have evolved, Chang said he has seen the pros and cons of the field’s growth.

“This is an area that is really hot,” Chang said. “It isn’t coincidental that this interest has coincided with emerging technologies, because the emerging technologies over the last decade have allowed us to look at the microbiome in many different ways….but this is a field where you can be easily consumed by the technology.”

Those techniques have changed alongside the trends of the broader field of microbiology, Chang said. Scientists interested in bacteria were once limited to studying what they could both find and grow in a lab dish, which left the vast majority of species unexplored. But new genetic techniques have brought those hidden worlds into the light, allowing scientists to take a more complete census of the bacteria present in a given sample from the Earth’s environment, or the special environments within the human body. With this added power has come a whole new menu of choices for scientists, from low-cost methods (i.e. T-RFLP) that can take a surface-level snapshot of the most common members of a microbial community to deeper sequencing that can identify rare microbes that may turn out to be relevant to disease (i.e. pyrosequencing).

“We have a number of techniques that have advantages and limitations,” Chang said. “What you use is dependent on what your question is and how deep you need to go.”

In Chang’s laboratory, the questions relate to the origins of inflammatory bowel diseases such as ulcerative colitis. A recent study looked at the microbial diversity within the colon, comparing the bacterial populations present in the mucosa of the proximal colon (near the small intestine) to the distal colon (near the anus). A T-RFLP analysis, which looks at fragments of ribosomal DNA in the mucosal samples, found that the microbes present in the two regions were distinct, with higher “richness” (the number of species present) observed in the proximal versus distal colon.

But to determine the role of the microbes in disease, just taking a census isn’t enough. The newest wave of microbiome research is focused on function, using techniques that find out what those billions of bacteria are actually doing inside our bodies or out in the world. With metagenomics, scientists can analyze all the genes from a given sample of soil, skin, or mucus, then group those genes by their functional role (metabolism, transport, etc.) using a technique developed by Argonne called MG-RAST. Many groups, including Chang’s team, are also interested in measuring host-microbe relationships - how the bacterial population affects the biology of their home organism.

“Sure we can say who’s there, but how do we actually know what’s important?,” Chang said.

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Posted by - Rob Mitchum

An Experimental Therapy from the “Bottom Up”

Posted at 9:24 am CT on June 7, 2011

superbugtransplantBy John Easton

Are we flushing away cures? In the last few years, physicians have developed a new respect for what used to be considered waste. Led by a maverick Australian physician, many US doctors have begun to test the curative capacity, when appropriately acquired, prepared and administered, of human excrement.

For once, it’s not the fiber that interests these digestive specialists; it’s the creatures that live in it, the intestinal flora. These indwelling microbes, when compared cell-to-cell, outnumber their hosts by about 10 to one. More than 1,000 different strains of bacteria co-exist peacefully in the typical healthy bowel. But when the delicate balance is altered by antibiotics or other causes, a few strains can become dominant, leading to severe diarrhea, inflammation, tissue damage, even death.

Bacterial aggregates derived from fecal matter have been used sporadically to treat digestive disease for more than 50 years. These were often last-ditch efforts aimed at restoring microbial balance for patients with raging intestinal infections. Fecal microbiota transplantation (FMT) - also known as fecal bacteriotherapy, among other names - is designed to calm a troubled bowel by reintroducing the vast diversity of collaborative bowel inhabitants after the usual, collegial mix has been disturbed.

The first FMT cases, dating back to 1958, were used to treat life-threatening infections caused by aggressive bacteria that had overwhelmed the bowel and eradicated the competition. When antibiotics were unable to control the infection, physicians were able to restore balance by collecting fecal matter from a healthy donor and injecting it into the patient’s colon. It was like a massive dose of probiotics, but delivered bottom up, rather than top down.

More recently, the approach has produced lasting remissions for a small number of patients with a common disease: ulcerative colitis. In 2003, a team led by the Australian physician, Thomas Borody, published a report [pdf] on successful treatment with this approach of six patients who had longstanding ulcerative colitis (UC). “Complete reversal of UC was achieved in all 6 patients following the infusion of human fecal flora,” the authors reported. “These 6 cases document for the first time the total disappearance of chronic UC without the need for maintenance treatment.”

After interviewing Borody, the Freakonomics podcast summarized the expanding medical role of human feces like this: “To paint it with a very broad brush: it could be that many maladies - from intestinal problems to obesity to disorders like multiple sclerosis and Parkinson’s and Alzheimer’s and perhaps even cancer - are related to damaged or missing gut bacteria; the solution therefore may lie in transplanting healthy bacteria into a sick person.”

“This is a fascinating idea, and the early studies show great promise,” said University of Chicago gastroenterologist David Rubin, associate professor of medicine. The notion has also made headway among patients. “We are getting at least one phone call a week from patients asking about the treatment and when we are going to start treating patients,” said colleague Stacy Kahn, instructor of pediatrics at the University of Chicago.

Although fewer than a dozen case reports involving ulcerative colitis have been published, Rubin and Kahn realized that many more patients were getting treated, largely without supervision or medical oversight, a development they called “alarming.” Several websites now provide guidance, almost like recipes, on how to perform this relatively simple procedure.

“This morning I decided to try a fecal transplant,” begins the saga of “Lucky Lindy,” posted on HealingWell.com. “I’ve been reading about it for months, and figured I might as well try … and while the process was a little gross it was easier than I anticipated. For anyone who is interested (and not grossed out), below is the process I used.” He goes on to list his entire protocol, with daily progress updates and cost-cutting tips, such as using a fork to stir the broth instead of a difficult-to-clean blender. read more

Posted by - Rob Mitchum