More Bugs Inside

I’ve written here before about the hygiene hypothesis, the idea that our focus, at least in the developed world, on maintaining an environment that is extraordinarily clean by historical standards, coupled with excessive use of antibiotics, may be contributing to a rise in conditions like asthma and auto-immune disorders.  The hypothesis is that the developing human immune system needs to be exposed to a diversity of different microbes in order to calibrate itself.  There is also the possibility that all of this emphasis on hygiene is getting rid of beneficial micro-organisms that are part of our internal bio-system.  Although we know that there are many different species of bacteria that call us home, we’re still at a very early stage in cataloging all the pieces of the puzzle, never mind how they go together.   The Human Microbiome Project, at the National Institutes of Health, is one effort to build our understanding of how our own personal ecosystems work.

The New York Times has an interesting article reporting on some of the recent developments in this field.  One of the obstacles to cataloging all the microbes that call us home has been that many of them cannot be grown in culture outside the human body.   This is a problem, especially since one might reasonably assume that the organisms that can’t survive in culture are those most specifically adapted to their host(s), and therefore of especial interest.  Researchers have now taken the approach of trying to collect and sequence bacterial DNA from the body.   The process is laborious, because the underlying microbiome is extremely complex.

To make sense of the genes that they’re gathering, they are sequencing the entire genomes of some 900 species that have been cultivated in the lab. Before the project, scientists had only sequenced about 20 species in the microbiome. In May, the scientists published details on the first 178 genomes. They discovered 29,693 genes that are unlike any known genes.

Scientists estimate that there are between 500 and 1,000 different species that colonize just the mouth, although any given person has only a subset of these.   They are even finding that internal organs, such as the lungs, which were previously thought to be sterile, because no one had ever been able to culture bacteria from healthy lungs, have their own set of microbial “colonists”.

A team of scientists at Imperial College London recently went hunting for DNA instead. Analyzing lung samples from healthy volunteers, they discovered 128 species of bacteria. Every square centimeter of our lungs is home to 2,000 microbes.

The Times story starts with a dramatic example of what can happen when this ecosystem is severely disrupted.

In 2008, Dr. Khoruts, a gastroenterologist at the University of Minnesota, took on a patient suffering from a vicious gut infection of Clostridium difficile. She was crippled by constant diarrhea, which had left her in a wheelchair wearing diapers. Dr. Khoruts treated her with an assortment of antibiotics, but nothing could stop the bacteria. His patient was wasting away, losing 60 pounds over the course of eight months.

(Clostridium is a genus of bacteria that includes the species responsible for tetanus, C. tetani, and for botulism, C botulinum.)

Dr. Khoruts finally tries treating his patient by introducing a sample of bacteria, collected from her husband’s feces, into her gut.  The results were fairly dramatic.  Both the diarrhea and other indications of infection disappeared within a couple of days.   The doctors compared specimens of bacteria from the patient’s gut before and after the treatment.

Before the transplant, they found, her gut flora was in a desperate state. “The normal bacteria just didn’t exist in her,” said Dr. Khoruts. “She was colonized by all sorts of misfits.”

Two weeks after the treatment, the patient’s internal microbial census had returned to normal.

This is a fascinating (if sometimes slightly gross) area of research. It is clear that there is a lot happening right in front of our eyes, as well as inside them, that we are just beginning to understand.