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Tummy Troubles

Research probes the trillions of microbes in our gut for health clues

By Christina Johnson   |   June 27, 2014

When 19th century French chemist and microbiologist Louis Pasteur peered through a microscope and correctly recognized bread yeasts as living microorganisms, the discovery fueled a backlash against leavened breads in America, with some health food advocates declaring self-rising quick breads nutritionally superior because of their lack of adulteration from microbial life.

Oh, how times have changed.

The discoveries of Pasteur and those who followed ultimately substantiated the germ theory of disease: the idea that microbes can invade us, grow their numbers and make us sick – or kill us outright. Arguably, germ theory and its corollary, that the eradication of germs can prevent or treat disease, has done more to save human lives, largely through sanitation and antibiotics, than any other single medical concept.

Gut Microbiome

But in the developed world, where the luxury of clean water can mostly be taken for granted, the pendulum is swinging the other way. Instead of scrubbing away microorganisms, consumers are paying top-dollar for probiotic soaps and probiotic face creams. Yogurt, miso, sauerkraut, even cookies promise to deliver “beneficial cultures.” C-sections are being viewed with a critical eye, as potentially robbing newborns of contact with their mother’s vaginal microbiome, which is believed to help train and prepare the newborn’s own immune system.

A new view of our relationship with the microbial world is emerging, one that is asking whether our sparkling kitchen floors, fast-food meals and overuse of antibiotics are changing the species diversity and relative abundances of our body’s microbes and by doing so, contributing to the modern First World plagues of obesity, diabetes, food allergies and inflammatory bowel disease.

“The short answer is yes. There is evidence that some of these effects are occurring,” said William Sandborn, MD, professor of clinical medicine at UC San Diego School of Medicine and chief of the Division of Gastroenterology at UC San Diego Health.

The microbiome refers to the 100 trillion or so microbes in and on our bodies. Much has been made of the fact that these microbes outnumber the body’s cells 10 to 1, but this overlooks a key point about our evolutionary détente with the microbial world.

Our microbial denizens are not distributed evenly throughout our tissues. They are largely concentrated to the tubing of our intestinal tracts and to the surface of our skins, our most obvious barrier to invasion.

“When barriers are breached, it brews trouble,” said Lars Eckmann, MD, a professor of medicine whose research focuses on the disease mechanisms underlying intestinal infections and the regulation of inflammation.

Gut Microbes

Indeed, one of the more interesting aspects of microbiome research at UC San Diego is the slow piecing together of how life-style choices, such as a high-fat Western diet and heavy drinking, can contribute to the breakdown of the barrier between us and them, causing what is
known as “leaky gut syndrome” and liver disease.

“We’ve known for a long time that people who are obese are prone to non-alcohol related fatty liver disease (NFLD),” said Bernd Schnabl, MD, professor in gastroenterology.

A high-fat diet has been shown to promote an overgrowth of gut bacteria that metabolize choline, an essential micronutrient that helps the liver secrete fats, Schnabl explained. It also promotes an overgrowth of microbes that produce compounds that make the intestinal wall more porous. This creates a double whammy for the liver: Without adequate choline, the liver cannot purge itself of lipids and is simultaneously being asked to filter bacteria and toxins leaking from the intestine. The assault can lead to NFLD, which now affects at least 20 percent of adults in the United States.

Schnabl’s research has shown that heavy alcohol consumption also changes the community structure of the gut’s microbiome, causing a population explosion of bacteria that synthesize lower amounts of fatty acids and metabolize ethanol into acetaldehyde. The liver is again hit by a  one-two punch: Ethanol and acetaldehyde both disrupt the normally tight junctures in the intestinal wall that prevent leaks into the blood stream, while fatty acids act to help maintain the intestinal wall’s health.

“The liver is the first organ to encounter whatever is leaking through the gut into the blood stream,” he said. The blood vessels in the intestinal wall feed the portal vein, which flows straight to the liver.

Alcohol’s effect on the microbiome may help explain why people with alcoholic hepatitis have such high rates of mortality (about 50 percent) even after they stop drinking, he said.

In experiments with mice, Schnabl and colleagues reversed alcohol’s pernicious effect on the gut and liver, to a degree, by supplementing the animals’ diets with the same fatty acids that the altered microbiome was synthesizing in lower quantities. Though a similar approach would not be recommended for humans because these fatty acids may also promote heart disease, the research is “a classic example of how we can look at changes in the microbiome and make an intervention,” Schnabl said.

Another disease that has been convincingly linked with an out-of-whack microbiome is Clostridium difficile colitis. The intestinal infection is caused by an overgrowth of the C. difficile bacterium and is associated with antibiotic use, usually in a hospital or nursing home setting.

“Historically, we have treated C. diff infections with antibiotics,” said Sandborn, who is also the director of the UC San Diego Inflammatory Bowel Disease (IBD) Center,  a new multidisciplinary clinical effort designed to serve the estimated 15,000 individuals in San Diego County who suffer from IBD.  “The problem is that as soon as you withdraw the antibiotics, the infection may reoccur because you’ve recreated the circumstances that gave rise to the infection to begin with.”

Gastroenterologists at UC San Diego have begun treating C. diff infections with fecal microbiota transplants, in which stool from a healthy donor is placed in a patient’s colon to re-establish healthy gut flora. The treatment has a very high success rate (greater than 90 percent) but is still considered experimental and does not yet have FDA approval.

“Fecal transplants are our first step in using microbiome approaches to treat C. diff,” he said.

Many other diseases could potentially be treated or monitored through microbiome approaches. Inflammatory bowel conditions, such as Crohn’s disease and metabolic syndrome disorders such as obesity, diabetes, high-blood pressure and cardiovascular disease, have all been linked to disruptions in a person’s gut flora.

“What is not yet clear is whether the diseases come first and then change the microbiome or whether it is the other way around and changes in the microbiome precede disease and are an important triggering factor,” Sandborn said.

Either way, microbiome approaches could offer promising new treatments for chronic First World diseases, for example:

If changes in the microbiome are shown to cause disease, researchers could create diet- and bacteria-oriented treatments. These would act to shift a patient’s microbiome to a state that would restore sustained health.

If the microbiome proves to be a marker for disease but not the cause of it, medical professionals could monitor a person’s fecal bacteria to gauge the degree to which treatments are working.

Neither of these types of approaches has been feasible in the past because, before advances in rapid DNA sequencing, it was impossible to identify the different species of gut microbes.

What you can do

Sandborn has a few suggestions for keeping your microbiome healthy:

  • Be cautious when considering taking antibiotics for bronchitis, a sore throat or an ear infection. Antibiotics are often not indicated for these three common conditions because they are usually caused by viruses, not bacteria.
  • If you do take antibiotics, try eating foods that contain probiotics, such as yogurt, miso soup or sauerkraut, after the course of antibiotics is done.
  • Eat a plant-based diet. The fiber in whole, plant-based foods feeds and supports a healthy community of gut bacteria.