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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 sulphur 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
sulphurous 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 sulphur 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. Sulphur-based preservatives are in most
processed foods, from instant potato to jams and dried fruit, as well as in most
wines, beers and ciders. Sulphur 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 kilometres 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 sulphur bacteria—knowledge that was to
prove useful in a very different quarter.

These mud-loving organisms, officially known as sulphate-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 sulphate in seawater.
The bugs make their own energy from these raw ingredients, converting sulphate
to sulphite and then creating a poisonous waste product: hydrogen sulphide, with
its telltale smell of rotten eggs. To humans, the compound is as toxic as
cyanide. In water, it rapidly becomes highly corrosive sulphuric acid.

In the late 1980s the oil industry was well aware how caustic by-products of
the sulphur-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 sulphur
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 odourless, mainly harmless gases—
hydrogen, nitrogen, carbon dioxide and 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 harbouring 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?

Sulphate-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 realised 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 sulphate-reducing bacteria predominate in marine sediments
where they use up hydrogen as well as sulphurous compounds. What’s more, on the
seabed these microbes get the better of methane-generating bacteria if sulphate
is present.

High levels of sulphur are also present in the typical Western diet. Could
sulphate-reducing bacteria be displacing methanogens inside the guts of people
who eat large quantities of meat, packed with sulphur-rich amino acids, and
processed foods and fermented drinks preserved with the ubiquitous sulphur-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 sulphate. Ten days on, the breath of half of
their subjects no longer showed significant traces of methane. By day 15,
sulphide levels in their faeces had shot up. When they stopped eating the added
sulphate methanogens returned while the sulphate-reducing bacteria went into
sharp decline. In another study, the Dunn team found that rural South Africans,
eating a diet low in sulphur, 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 sulphate-reducing bacteria in
the faeces 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 sulphated seaweed. Bacteria in
general had been implicated in the disease, but could the sulphate 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 sulphate 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 sulphate-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 diarrhoea
in the colon.

Nevertheless, not everyone harbouring the sulphate-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 sulphate-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 sulphate-reducing bacteria are linked to bowel disease
but others are not. By studying mutant strains genetically engineered not to
make hydrogen sulphide, he hopes to find out whether it is the bacterial
invasion of gut cells alone that causes damage, or whether the sulphide
by-products are to blame, or indeed both. Gibson hopes this will reveal how
sulphate-reducing bacteria can cause colitis.

Defective cells

Meanwhile, an Australian abdominal surgeon has already found one way in which
sulphide 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 oxidise 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 sulphides 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 sulphur-amino acids as they are
digested. Cummings’s team believes these feed bacteria in the same way that
other sulphur compounds do. A preliminary study at the Dunn shows that as meat
consumption rises from 60 to 600 grams per day sulphates in the urine double,
and sulphides in faeces increase tenfold. A diet rich in meat has long been
implicated in colon cancer, and Cummings suspects that the toxic sulphides
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
sulphur 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 sulphur-amino acids harmless. Carbohydrate fuels the
growth of beneficial bacteria which snap up the sulphur amino-acids to
incorporate into their own proteins. The end result isn’t harmful sulphide, but
lots of beneficial “biomass”—bacterial bulk that helps to speed the
passage of faeces 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 sulphur in our diet is a large family of sulphur
additives in foods and drinks: sulphur dioxide, sulphites, bisulphites,
metabisulphites and sulphates, known in Europe by E number codes E220 to E227,
but often collectively called “sulphur dioxide”. These sulphur 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
sulphur-free—packaged salads are “gassed” with sulphur 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 sulphur 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 sulphur 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 recognises an
acceptable daily intake for sulphur-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 sulphur people typically consume, by measuring
their dietary intake and monitoring the amount of sulphate excreted in urine.
“The aim is to discover how much sulphur we are getting from protein and how
much from sulphur 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 sulphate-reducing bacteria. If
a link between Desulfovibrio bacteria, gut disease and a dietary source
of sulphur 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.