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By Gail Vines
What's the difference between the contents
of your bowels and the noxious black sludge at the bottom
of an estuary? Not a lot perhaps -- particularly if you
live on a diet of junk food.
The same
sulfur loving bacteria that give mud in estuaries and ocean
sediments their pungent, rotten-egg smell may have invaded
your gut.
In the sea, they are notorious troublemakers
with a penchant for corroding oil pipelines, and their effect
on human passageways may be equally devastating.
All these microbes need to flourish
in your guts is a good supply of sulfurous
compounds. And that's where your diet comes in.
Eat large amounts of animal
protein and processed food and you could be giving
these bad bugs everything they need to triumph at the expense
of your natural healthy gut microbes.
Over the past decade, the researchers
doing this work have steadily accumulated evidence to implicate
sulfur bacteria in a range of human diseases from inflammatory
bowel diseases to colon cancer.
"It's a potential bombshell,"
says John Cummings, head of the "gut group" --
the team pioneering this type of work at the Dunn Nutrition
Unit at Addenbrooke's Hospital in Cambridge. Sulfur-based
preservatives are in most processed foods, from
instant potato to jams and dried fruit, as well as in most
wines, beers and ciders.
Sulfur compounds are one of the world's
oldest food additives, used by the ancient Greeks and Egyptians
to preserve wine, and widely regarded as both versatile
and safe. So if these foods do encourage the growth of alien
microbes that are linked to disease, the food and drinks
industry could face a crisis to rival salmonella or BSE.
The story involves a series of coincidences
and begins 500 kilometers north of Cambridge, in the port
of Dundee on the east coast of Scotland. There, in the mid-1980s,
two PhD students from Dundee University, Glenn Gibson and
George Macfarlane, were studying the ecology of the Tay
estuary. "As it happens, the results weren't particularly
exciting," chuckles Gibson. But the young researchers
did learn a lot about sulfur bacteria -- knowledge that
was to prove useful in a very different quarter.
These mud-loving organisms, officially
known as sulfate-reducing bacteria, find plenty to feast
on in the oxygen-free (anaerobic) sea sediments. That's
because they can exploit both the hydrogen that comes from
the fermentation of countless microbes in the stagnant mud,
and the plentiful sulfate in seawater.
The bugs make their own energy from
these raw ingredients, converting sulfate to sulfite and
then creating a poisonous waste product: hydrogen sulfide,
with its telltale smell of rotten eggs.
To
humans, the compound is as toxic as cyanide.
In water, it rapidly becomes highly corrosive sulfuric acid.
In the late 1980s the oil industry was
well aware how caustic byproducts of the sulfur-loving organisms
could wreck their pipework, but no one yet imagined that
they could also be causing trouble in the human gut. This
idea was to emerge from multidisciplinary teamwork as Macfarlane
and Gibson moved south to Cambridge, to join Cummings and
his gut group.
The timing was good for the two young
microbiologists. "Researchers
were discovering just how important the gut bacteria are
in health and disease," says Cummings. His own team's
decision to pursue this line of enquiry was to lead them
eventually to finger the sulfur lovers as the agents of
disease.
Something
In The Wind
The quest began in an unlikely place
-- with the gases made by gut bacteria that people give
off when they belch or fart. The team devised an elegant
technique to provide the first accurate measurements of
the composition of intestinal gas in healthy people.
For 36 hours, volunteers lived in a
small airtight room, while researchers controlled the flow
of air through it. By measuring the difference in the concentration
of gases in the air entering and leaving the room, the investigators
could determine which gases were coming from volunteers.
The results, published in 1992, were
a surprise. Everyone knew that gut bacteria churn out a
variable mix of odorless, mainly harmless gases --
-
hydrogen
-
nitrogen
-
carbon
dioxide
-
methane
But the team was surprised by how little
hydrogen they found in the air leaving the room -- given
the chemical composition of the foods the volunteers had
eaten.
Something in the gut was gobbling up
much of the available hydrogen. Another finding was puzzling
too:
some
people produced substantial amounts of methane, while others
produced much less, or none at all.
The methane could have come from only
one source: methane-producing bacteria, otherwise known
as methanogens. These bacteria consume hydrogen, which would
explain the low levels of this gas given off by people harboring
methanogens. But breath tests designed to detect methane
suggest that only about half of the people living in North
America and Northern Europe have methanogens living in their
gut. Why do some people have them, while others do not?
And what is soaking up the hydrogen if methanogens aren't?
Sulfate-reducing bacteria, first reported
in the human gut in the late 1970s, looked like good contenders.
Gibson and Macfarlane, recalling their experiences in the
Tay estuary, quickly realized that this was not such a preposterous
idea. After all, microbial fermentation in the final part
of the gut, the distal colon, provides anaerobic conditions
on a par with those in marine muds.
And sulfate-reducing bacteria predominate
in marine sediments where they use up hydrogen as well as
sulfurous compounds. What's more, on the seabed these microbes
get the better of methane-generating bacteria if sulfate
is present.
High levels of sulfur are also present
in the typical Western diet. Could sulfate-reducing bacteria
be displacing methanogens inside the guts of people who
eat large quantities of meat, packed with sulfur-rich amino
acids, and processed foods and fermented drinks preserved
with the ubiquitous sulfur-based food additives?
Fighting
Back
To test this idea the team asked volunteers
who normally produce methane in their breath to eat a diet
rich in sulfate. Ten days on, the breath of half of their
subjects no longer showed significant traces of methane.
By day 15, sulfide levels in their feces had shot up. When
they stopped eating the added sulfate methanogens returned
while the sulfate-reducing bacteria went into sharp decline.
In another study, the Dunn team found that rural South Africans,
eating a diet low in sulfur, were virtually all methane-producers.
Intrigued, the Dunn researchers next
began to wonder if these gut microbes affected human health.
They compared the levels of sulfate-reducing bacteria in
the feces of healthy people and in patients suffering from
ulcerative colitis, a serious inflammatory bowel disease
that afflicts up to one in a thousand people in Britain
and the US.
Work done
in the US during the 1970s showed that "germ-free"
lab animals lacking any gut bacteria do not develop colitis-like
symptoms, even when exposed to irritants such as sulfated
seaweed.
Bacteria in general had been implicated
in the disease, but could the sulfate reducers be major
players?
The team's results were striking.
Virtually
everyone with colitis -- 96 per cent of the sufferers tested
-- played host to the sulfate lovers, but only 50 per cent
of the healthy people did.
In particular, the gut of someone with
colitis was home to large numbers of sulfate-reducing bacteria
from the genus Desulfovibrio. "There turned out to
be more subtypes of these bacteria in the human gut than
we had expected, with some more active or virulent than
others," says Cummings.
One strain isolated from the colons
of people with colitis showed signs of being adapted to
life in an inflamed gut, Gibson found. Growing in a continuous
culture "gut model" fermenter in the laboratory,
the strain can survive high flushing rates that simulate
diarrhea in the colon.
Nevertheless, not everyone harboring
the sulfate-reducing bacteria was ill. And some ill people
did not have the bacteria.
So, what
exactly is their link with colitis?
Do they cause it, exacerbate it, or
simply take up residence in a diseased colon because they
can? Macfarlane points out that pinpointing an individual
cause of ulcerative colitis is virtually impossible because
it is a chronic inflammatory condition intimately involved
with the body's immune response.
"It may be that sulfate-reducing
bacteria contribute to the maintenance of the disease rather
than kick it off," he cautions. "It is difficult
to tie gut disease to a particular organism," adds
Gibson. The gut is home to at least 400 species of microbes,
many of which are difficult or impossible to grow in lab
cultures -- and the vast majority of which are harmless.
Gibson, who is now at the Institute
of Food Research in Reading, is investigating why some sulfate-reducing
bacteria are linked to bowel disease but others are not.
By studying mutant strains genetically engineered not to
make hydrogen sulfide, he hopes to find out whether it is
the bacterial invasion of gut cells alone that causes damage,
or whether the sulfide byproducts are to blame, or indeed
both. Gibson hopes this will reveal how sulfate-reducing
bacteria can cause colitis.
Defective
Cells
Meanwhile, an Australian abdominal surgeon
has already found one way in which sulfide might damage
the gut. In the 1980s Bill Roediger, at the Queen Elizabeth
Hospital in Woodville, near Adelaide, first noticed that,
in people with ulcerative colitis, the epithelial cells
that line their colons don't function normally. These cells
lack the ability to oxidize a vital fatty acid called butyrate,
which is normally their main nutrient.
This metabolic abnormality could be
the first step in the development of the disease: it seems
to precede the start of obvious colitic changes in the colon.
Significantly, in 1993, he showed that exposure to sulfides
selectively inhibits the ability of colon cells to use butyrate.
More work is needed to understand the
link between diet, bacteria and disease, says Macfarlane.
Such research could tell us how to encourage beneficial
bacteria and freeze out the harmful ones. One day there
might even be a vaccine against harmful gut organisms. But
at the moment, the most hopeful strategy is to encourage
a process of "natural displacement" through changing
what we eat.
Meat and other foods high in protein
release sulfur-amino acids as they are digested. Cummings's
team believes these feed bacteria in the same way that other
sulfur compounds do. A preliminary study at the Dunn shows
that as meat consumption rises from 60 to 600 grams per
day sulfates in the urine double, and sulfides in feces
increase tenfold. A diet rich in meat has long been implicated
in colon cancer, and Cummings
suspects that the toxic sulfides released by these microbes
might promote cancerous changes in gut cells by damaging
their DNA.
But what about vegetarians? Are they
off the hook? Vegetable protein -- notably in beans and
seeds -- also contains amino acids with sulfur groups attached,
so why are vegetarians at lower risk of colon cancer? The
crucial difference could be in the balance of nutrients.
In plant foods, protein comes in carbohydrate-rich packages.
Cummings suspects that this combination could make the sulfur-amino
acids harmless.
Carbohydrate fuels the growth of beneficial
bacteria which snap up the sulfur amino-acids to incorporate
into their own proteins. The end result isn't harmful sulfide,
but lots of beneficial "biomass" -- bacterial
bulk that helps to speed the passage of feces through the
gut. It is possible, he says, that carnivores who eat lots
of plant foods and carbohydrates along with their meat could
be protected too.
The second major source of sulfur in
our diet is a large family of sulfur additives in foods
and drinks: sulfur dioxide, sulphites, bisulphites, metabisulphites
and sulfates, known in Europe by E number codes E220 to
E227, but often collectively called "sulfur dioxide".
These sulfur
compounds are the major preservative in the Western diet.
"They are in hundreds and hundreds
of foods," says Cummings, everything from sausages
and burgers to jam, dried raisins and instant soup. Even
fresh foods may not be sulfur-free -- packaged salads are
"gassed" with sulfur dioxide to prolong their
shelf life.
Soft drinks, wines, beers and ciders
can contain widely varying levels, which do not have to
be listed on the label. It is detoxified by enzymes in the
liver and kidneys which makes sulfur dioxide "a very
safe additive -- about the safest thing we've got that does
that job", says Bronik Wedzicha, professor of food
science at the University of Leeds.
Nonetheless, a shadow of doubt has already
been cast on this venerable preservative. Especially lavish
use -- in American salad bars, for instance -- has now been
curtailed, after allergic reactions particularly in people
with asthma.
Although sulfur additives are in such
a huge variety of foods, no one has yet systematically monitored
the amount ingested with an average Western diet. In Britain,
the Ministry of Agriculture Fisheries and Food recognizes
an acceptable daily intake for sulfur-based preservatives.
But if you eat large amounts of processed
food, washed down with beer or wine, your daily consumption
could be well above this level. So, with funding from MAFF,
Cummings and his colleagues are assessing how much sulfur
people typically consume, by measuring their dietary intake
and monitoring the amount of sulfate excreted in urine.
"The aim is to discover how much
sulfur we are getting from protein and how much from sulfur
additives," says Cummings.
Although the evidence is not yet in,
Cummings suspects that other inflammatory bowel diseases,
such as Crohn's disease, as well as the ill-defined irritable
bowel syndrome, could also be linked to sulfate-reducing
bacteria.
If a link between Desulfovibrio bacteria,
gut disease and a dietary source of sulfur can be tied down
and the mechanism identified, it will mark a major turning
point in the way we think about human health. As bacterial
warfare is waged in the human gut, our health may yet depend
on feeding an army of friendly microbes and starving the
foe into submission.
New Scientist,
August 8, 1998
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