Unlocking the Secrets of the Microbiome

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Modern technology is making it possible for medical scientists to analyze inhabitants of our innards that most people probably would rather not know about. But the resulting information could one day save your health or even your life.

I’m referring to the trillions of bacteria, viruses and fungi that inhabit virtually every body part, including those tissues once thought to be sterile. Together, they make up the human microbiome and represent what is perhaps the most promising yet challenging task of modern medicine: Determining the normal microscopic inhabitants of every organ and knowing how to restore the proper balance of organisms when it is disrupted.

Proof of principle, as scientists call it, has already been established for a sometimes devastating intestinal infection by the bacterium Clostridium difficile. This infection, popularly called C. diff, often occurs when potent antibiotics wipe out the normal bacterial inhabitants of the gut that otherwise keep it in check.

When all else fails to clear up a recurrent C. diff infection, the Food and Drug Administration has approved treatment with a fecal transplant from a healthy gut presumed to contain bacteria that can suppress C. diff activity. The treatment is highly effective, with a cure rate in excess of 90 percent.

Under the auspices of the National Institutes of Health, a large team of scientists is now engaged in creating a “normal” microbiological road map for the following tissues: gastrointestinal tract, oral cavity, skin, airways, urogenital tract, blood and eye. The effort, called the Human Microbiome Project, takes advantage of new technology that can rapidly analyze large samples of genetic material, making it possible to identify the organisms present in these tissues.

Depending on the body site, anywhere from 20 percent to 60 percent of the organisms that make up the microbiota cannot be cultured and identified with the older, traditional techniques used by microbiologists.

If the institutes’ five-year project succeeds in defining changes in the microbiome that are associated with disease, it has the potential to transform medicine, assuming ways can be found to correct microbial distortions in the affected tissues.

Here are some of the demonstration projects already underway:

Skin: Dr. Martin J. Blaser, microbiologist and director of the human microbiome program at New York University School of Medicine, is directing examination of the organisms on the skin of 75 people with and without psoriasis, checking whether agents used to treat the condition adversely alter the microbiome.

Vagina: Jacques Ravel at the University of Maryland School of Medicine and Larry J. Forney at the University of Idaho are studying 200 women to determine the microbial changes that may result in a common and difficult-to-control infection called bacterial vaginosis, which afflicts more than 20 million American women of childbearing age.

Blood: At Washington University in St. Louis, Dr. Gregory A. Storch, a specialist in pediatric infectious disease, and colleagues are examining the role of viruses and the immune system in the blood and respiratory and gastrointestinal tracts of children who develop serious fevers that result in some 20 million visits a year to hospital emergency rooms.

Gastrointestinal tract: Claire M. Fraser-Liggett, a microbiologist, and Dr. Alan R. Shuldiner, a geneticist, both at the University of Maryland School of Medicine, are exploring how the microbiome affects the body’s use of energy and the development of obesity.

Previous studies have already found differences in the gut microbiota of lean and obese adults. There is also evidence that the typical high-calorie American diet rich in sugar, meats and processed foods may adversely affect the balance of microbes in the gut and foster the extraction and absorption of excess calories from food.

A diet more heavily based on plants — that is, fruits and vegetables — may result in a microbiome containing a wider range of healthful organisms. In studies, mice that had a microbiota preconditioned by the typical American diet did not respond as healthfully to a plant-based diet.

Compared to lean mice, obese mice have a 50 percent reduction in organisms called Bacteroidetes and a proportional increase in Firmicutes, and lean mice get fat when given fecal transplants from obese mice. A similar shift has been observed in people, and the distorted ratio of organisms was shown to reverse in people who lose weight following bariatric surgery.

There is also evidence that microbes residing in the gut can affect distant sites through their influence on a person’s immune responses. This indirect action has been suggested as a possible mechanism behind rheumatoid arthritis. In mice, certain bacteria in the gut have been shown to foster production of antibodies that attack the joints, resulting in the joint destruction typical of rheumatoid arthritis.

Similarly, studies have suggested a role of the gut microbiota in the risk of developing neuropsychiatric illnesses like schizophrenia, obsessive-compulsive disorder, attention deficit hyperactivity disorder, autism and even chronic fatigue syndrome. Researchers have suggested that in genetically susceptible people, altered microbes in the gut may disrupt the blood-brain barrier, leading to the production of antibodies that adversely affect normal brain development.

Among the challenges in elucidating the microbiome’s role in health and disease is determining whether changes found in the microorganisms inhabiting various organs are a cause or an effect. Most of what is already known about the microbiota in people with various health problems is based on observation, making it difficult to say which came first: the disease or the disrupted microbiota.

Animal studies like those mentioned above are a clue but not proof of a similar effect in people. Until therapeutic studies now underway are completed, people with conditions thought to be influenced by the microbiome have no choice currently but to rely on possible treatments suggested by animal research and some preliminary human studies.

For example, people with irritable bowel syndrome, inflammatory bowel disease, allergic disorders and infections with drug-resistant organisms may benefit from taking probiotics, though some probiotics sold in health food and drugstores may be ineffective. It may be necessary to tailor-make the remedy for each condition or even each patient.

Meanwhile, people interested in fostering a health-promoting array of gut microorganisms should consider shifting from a diet heavily based on meats, carbohydrates and processed foods to one that emphasizes plants. As Dr. Jeffrey Gordon, a genomics specialist at Washington University School of Medicine, told The Times last year, “The nutritional value of food is influenced in part by the microbial community that encounters that food.”