Dr. Chris
New Scientist January 19 , 2011
Diabetes and even obesity, as well as Parkinson's disease, might be
cured just by replacing the bacteria in your gut
A FEW years ago, John Gillies had trouble picking up his grandchild. He
would stand frozen, waiting for his Parkinson's disease to relinquish
its hold and allow him to move. Then in May 2008, Gillies was given
antibiotics to treat constipation, and astonishingly his Parkinson's
symptoms abated. What on earth was going on?
Thomas Borody, a gastroenterologist at the Centre for Digestive Diseases
antibiotics because he had found that constipation can be caused by an
infection of the colon. "He has now been seen by two neurologists, who
cannot detect classic Parkinson's disease symptoms any more," says
Borody.
Borody's observations, together with others, suggest that many
conditions, from Parkinson's to metabolic disorders such as obesity,
might be caused by undesirable changes in the microbes of the gut. If
that is true, it might be possible to alleviate symptoms with
antibiotics, or even faecal transplants
bowel flora to a healthy state.
Borody uses faecal transplants to cure people infected by the superbug
Clostridium difficile, and to alleviate chronic constipation. Over the
past decade, Borody has noticed that some of his patients also see
improvements in symptoms of their other diseases, including
Parkinson's, multiple sclerosis (MS), chronic fatigue syndrome (CFS)
and rheumatoid arthritis. "Some CFS patients, given a faecal
transplant, will regain their energy quite dramatically, and their
foggy brains will get better," says Borody.
To test a possible link between the gut and Parkinson's disease, Borody
and neurologist David Rosen of the Prince of Wales Private Hospital in
Sydney are embarking on a pilot study, hoping to recruit people with
both constipation and Parkinson's. The plan is first to treat them with
antibiotics and eventually with faecal transplants. They hope both
faecal transplants and antibiotics will treat gut infection and hence
Parkinson's.
Rosen is cautious: "I wouldn't for one minute be suggesting that this
is the next cure," he says. But the idea that Parkinson's could be
caused by bacteria dovetails with work by neuroanatomists Heiko Braak
and Kelly Del Tredici at the University of Ulm in Germany.
In 2003, Braak and Tredici showed that damage to the nervous system in
Parkinson's progresses from the vagus nerve in the lower brain stem to
the higher regions of the brain and eventually to the cerebral cortex.
They also found damage in the enteric nervous system, which controls
the gastrointestinal (GI) tract and communicates with the brain via the
vagus nerve. This discovery prompted them to suggest that Parkinson's
might be caused by a bug that breaks through the mucosal barrier of the
GI tract and enters the central nervous system via the vagus nerve
(Journal of Neural Transmission, DOI: 10.1007/s00702-002-0808-2
So what about the dramatic improvements seen in people with autoimmune
diseases, such as rheumatoid arthritis, after faecal transplant?
Borody's hypothesis is that an infection of the colon releases antigens
into the bloodstream, which trigger an immune response. Unless
something is done to completely clear the colon of the antigen, the
immune response is relentless, eventually leading to systemic
inflammation that manifests itself as an autoimmune disease.
Interpreting Borody's results requires extreme caution. However, there
is evidence from animal models that intestinal microbes can influence
autoimmunity. For instance, Alexander Chervonsky
University of Chicago and colleagues have linked microbes in the gut to
type 1 diabetes, an autoimmune disorder caused by the destruction of
insulin-secreting pancreatic cells. Over 80 per cent of a particular
breed of engineered mice that are kept germ-free develop type 1
diabetes. When the same mice were dosed with a cocktail of bacteria
similar to those present in the human gut, only 34 per cent of the mice
developed type 1 diabetes, suggesting a connection between gut flora
and autoimmune diabetes (Nature, DOI: 10.1038/nature07336
Researchers are becoming increasingly aware of the link between gut
flora and autoimmunity, says Arthur Kaser, an expert on inflammation
and intestinal flora at the University of Cambridge. For instance, mice
designed to develop autoimmune diseases do so in some labs but not in
others. The discrepancy is down to differences in the intestinal flora
of the mice. "Intestinal microbiota has a dramatic effect on [what] we
currently consider as autoimmune disease," says Kaser.
Evidence for such links in humans is also growing: Anne Vrieze of the
Academic Medical Center in Amsterdam, the Netherlands, and colleagues
studied 18 obese men with metabolic syndrome, a collection of symptoms
that includes low insulin sensitivity. The group received faecal
transplants - either of their own stool or stool from lean, healthy
donors.
The results of this first double-blind trial were presented at the
annual meeting of the European Association for the Study of Diabetes in
Stockholm, Sweden, in September. The researchers found that, six weeks
after the infusions, insulin sensitivity improved significantly in the
nine men who received donor stool.
Gut flora has also been linked to obesity. Over the past five years,
Jeffrey Gordon
in St Louis, Missouri, and colleagues have shown that there are marked
differences in the gut flora of obese and lean individuals. Their
analysis suggested that the microbes in obese individuals are releasing
nutrients from food that would have remained undigested in lean
individuals. Importantly, they showed that transferring the microbiota
from obese mice into lean mice caused the lean mice to put on weight
(Nature, DOI: 10.1038/nature05414
So can you reverse obesity in humans by transferring gut microbes from
lean people into obese people? It's a question that Alex Khoruts
University of Minnesota Medical School in Minneapolis, hopes to answer.
He is planning a trial in which obese people will be given faecal
transplants, either of their own faeces or samples taken from lean,
healthy donors. "The idea is to alter the composition of colon flora,
and see whether it has an impact on obesity," says Khoruts.
"This is absolutely exciting," says Kaser. But he insists that we are
far from understanding the nature of the microbes that populate our
body - after all, the colon alone contains nine times as many bacterial
cells as there are human cells in the body. And we don't yet know what
constitutes "healthy" colon flora. This will make it difficult to
justify any large-scale adoption of faecal transplants, he adds. If
intestinal bugs are indeed causing autoimmune diseases, "you don't want
to treat one disease and introduce another", says Kaser.
Nonetheless, he is convinced that human microbiota will become
increasingly important in our understanding of disease. "Textbooks will
have to be rewritten when we consider the contribution of intestinal
microbiota," he says. "We have an elephant in the room that has not yet
been appreciated."
[Issue 2796 of New Scientist magazine]
