Jemima Stockton

Gut Flora: A Digestible Account of Probiotics

Man's best Friend

Figure 1: A substance in porridge oats, known as beta glucans, helps gut microbes to grow

Every morning I eat porridge, and then, as the warm oats land in my belly and their complex carbohydrates burn slowly to energise my body for hours, I develop an internal glow, albeit less radiant and a lot more natural than the orange kids in the 1980's advert for Ready Brek. Many may find the resemblance of my preferred breakfast to wallpaper paste a little repulsive, but close your eyes, if you must, tuck into a bowl, and experience the amazing Duracell battery-like powers of porridge.

You won't be alone in enjoying your breakfast either (figure 1, right),

because the friendly bacteria in your gut thrive on it too. A substance

in the oats, known as beta glucans, helps them to grow. So persevere with

that daily helping of wallpaper paste because it's good for you, and it's

good for the bugs in your innards, which means it's doubly good for you

!

Figure 2: Ruminants are strict vegetarians and have evolved a specialised intestinal compartment containing bacteria capable of breaking down otherwise indigestible plant materials such as cellulose.

If your body's hospitality to bacteria comes as an unwelcome surprise,

worry not. The world is teeming with good bacteria that help to sustain

life on Earth by carrying out crucial tasks. For example, cyanobacteria

convert light energy into chemical energy using the process of photosynthesis,

a by-product of which is oxygen. Rhizobacteria, on the other hand, convert,

or fix, nitrogen in the air into a form which leguminous plants can use,

enabling them to grow. And the benefits don't stop there. Some mammals,

such as ruminants (figure 2,left), use bacteria to boost the nutritional

value of their diet. Ruminants are strict vegetarians and have evolved

a specialised intestinal compartment containing bacteria capable of breaking

down otherwise indigestible plant materials such as cellulose. This means

that smaller, bite-sized, animals can relax, safe in the knowledge that

their bigger counterparts are well fed. In short, microorganisms help

humans to breathe easy whilst they enjoy vitamin-rich legumes, and eat

meaty ruminants like cattle.

In other words, miniscule microbes can achieve massive feats that utterly

belie their size. But a lone bacterium is a powerless and vulnerable single

cell. Its survival depends entirely on its external environment.

Indeed, bugs like these rely on the bodies of more sophisticated, multicellular

organisms to provide protection, organic nutrients and growth factors,

and steady environmental conditions. Given the right environment, bacteria

can double their numbers roughly every half hour, producing a formidable

force from just a single cell within a short space of time. In fact, such

is their productivity that whilst a 500kg cow can generate 1kg of protein

per day, a cow-sized mass of bacteria can produce 10 000 times this amount.

HUMAN BOWEL FLORA

Not surprisingly the human body provides an appealing habitat for many

bacteria as it maintains a constant temperature. Indeed, each of us plays

host to trillions of bacteria, known as our 'normal flora', the vast bulk

of which (85%) are harmless, if not beneficial. But 'bacterial residency'

is not always granted by default. Each of us employs a menacing array

of anti-microbial defences to make sure our blood, lungs and brain remain

bug-free zones, although there are plenty of areas readily accessible

to microbes and the respiratory, urogenital, and digestive tracts provide

prefect 'tropical' living conditions favoured by many types bacteria.

The skin also provides sites for colonisation with warm, damp areas, such

as the groin and between the toes, proving particularly popular.

But of all the places available to our normal flora, the gut is the most

heavily occupied. Why? Because the human digestive tract offers the microbe

what New Zealand offers the tourist: a massive variety of environments

creating opportunities for a plethora of activities. It is a multicultural

melting pot. With something for almost everyone, it's no surprise that

the human gut hosts 80% of the body's normal flora and includes more than

500 different bug species.

Though each microbe is tiny, the trillion or so that live in our guts

and outnumber the human cells that make up the rest of the body, add at

least a kilo in weight to each of us. But if, in the name of weight-loss,

you're tempted to shed your body's bacterial load by soaking in a bath

of Toilet Duck, or gulping down a bottle of Dettol, you might be wise

to reconsider. Our normal flora produces essential nutrients and generates

by-products that reduce the risks of developing certain cancers, digestive

disorders, and heart disease. It serves our bodies from the cradle to

the grave.

Figure 3: With no pre-existing bacteria to demand competition, bugs ingested during the birth process colonise the infant gut within days.

HOW BACTERIA COLONISE NEWBORN BABIES

Actually, bugs start making us their home before we even hit the crib.

When a germ-free baby is released from the sterile confines of its mother's

womb, it swallows a mouthful of muck. So, upon entering a world full of

germs ever keen to enter a fresh new body, the bugless babe is at once

no more. It has morphed into a vessel accommodating a mass of microbes,

just like its fellow human beings.

Being born is invariably a messy business but the route taken will determine

the nature of the mess ingested. Pop out through the birth canal and you

will gulp down your mother's vaginal and faecal flora including a wholesome

mix of Lactobacillus, Bifidobacterium, E.coli and Enteroccoccus. But burst

out through your mother's abdomen, along the path originally promoted

by Julius Caesar, gives you a mouthful of an entirely different assortment:

hospital-acquired bugs such as Clostridium and Streptococcus are often

the main ingredients of a Caesarian baby's bacterial breakfast.

With no pre-existing bacteria to demand competition, bugs ingested during

the birth process colonise the infant gut within days. Over the first

few days of life, additional types bacteria join the gut flora. Staphylococcus

aureus, for example, is transferred from the mother's nipple during suckling,

and through kisses and cuddles from doting relatives.

BREAST IS BEST

Some beneficial microbes, like bifidobacteria, receive a helping hand

to become established from proteins in breast milk . As a result, after

just a few weeks, this bug makes up over 90% of a breastfed baby's intestinal

flora. Bifidobacteria make the baby's gut acidic which creates a barrier

against infection with bugs which the child has yet to develop natural

immunity, including many acid-intolerant disease-causing microbes. But

bifidobacteria fail to thrive on the diet of proteins provided by the

modified cow's milk used in formula feeds, meaning a formula-fed baby

is more prone to infection with harmful gut germs.

Colonisation of the gut by disease-causing microbes can also lead to

a life-threatening condition known as necrotising enterocolitis which

is common amongst pre-term (premature) babies. For every 10 babies affected,

approximately 3 will die and 2 will suffer long-term effects of their

illness. Many premature births are the result of complications that necessitate

caesarian delivery and breastfeeding is often delayed by several days

whilst they are receiving intensive care. Together, these factors can

lead to poor quality gut flora and a higher susceptibility to necrotising

enterocolitis. Fortunately, recent research indicates that administration

of certain probiotic (click for the definition of

probiotic) Lactobacillus and Bifidobacterium strains to susceptible

infants can decrease the risk of developing the disease.

Amongst older children, the introduction of solid foods into a baby's

diet will change the gut flora again, as new substances selectively promote

the growth of different bacteria. At the age of about two, once completely

weaned off breast milk and onto more grown-up foods such as bangers and

mash, mushy peas and macaroni cheese, the floral composition of a child's

gut will resemble that of a normal adult - Bacteroides, Bifidobacterium,

Eubacterium, and Peptostreptococcus predominate. Each of the different

species residing in the digestive tract has a unique set of adaptations

making a particular environment suitable for colonisation. And the large

variety of species renders almost every part of the gut a cosy niche for

some bug or another.

WHY ANTIBIOTICS CAN UPSET YOUR STOMACH

Like settled squatters, these microbial populations are hard to shift,

but ageing, and alterations in the gut environment caused by antibiotics

can force changes. In general, young people have a healthier gut flora

their grandparents, which is one of the reasons why older people are more

susceptible to intestinal upsets than their younger counterparts. In the

case of antibiotics, unfortunately they don't just kill the bad guys -

they also knock out members of the intestinal flora, allowing the numbers

of disease-causing bacteria, previously held in check by the predominating

friendly bacteria, to begin to multiply. If sufficient numbers of these

disease-causing bugs emerge, they can cause a variety of symptoms, including

diarrhoea. A common culprit responsible for this type of antibiotic-associated

diarrhoea is a native colonic bug called Clostridium difficile. It produces

a toxin which damages the bowel wall, triggering diarrhoea. However, treatment

with a yeast known as Sacchromyces bombardii can relieve the symptoms,

possibly because the yeast can destroy the toxin, thereby allowing the

damaged bowel wall to heal.

SO HOW DO DIFFERENT BACTERIA COLONISE THE INTESTINE ?

Microbial access to the digestive tract is via the top. It is a piece

of cake: bugs can hitch a lift on food hand-delivered to the mouth. Obviously,

conditions must be conducive to growth for a species to set up home in

a particular niche, but bugs searching for accommodation in the digestive

tract must also be able to withstand the conditions of sites through which

they must pass.

Just the thought of an imminent meal can make a hungry person dribble.

This is because the brain tells the mouth to prepare for the arrival of

food by secreting saliva which makes a chemical and mechanical contribution

to digestion. It contains amylase that begins the digestion of starchy

foods, such as potatoes and rice, and it moistens and lubricates food

to help swallowing. Aside from its roles in the digestive process, saliva

also contains antimicrobial substances that inhibit the growth of bacteria.

But Streptococcus mutans is a big fan of the mouth area and can easily

side-step these defences. It also has a particular fondness for sweet-toothed

mouths and, in the presence of cakes and biscuits, it forms films, or

'plaques', on the surfaces of teeth. Bacteria thriving within these plaques

turn sugar into acid that then burns holes in teeth. But, before you rush

off in search of your toothbrush, it's worth noting that the benefits

of this bug's activities are not exclusive to dentists, they extend to

you too. The sheer weight in numbers of S.mutans suppresses the growth

of another bacterium found in the mouth, Streptococcus pneumoniae, which

can cause pneumonia and meningitis. By restricting the numbers of S.pneumoniae,

S.mutans decreases the risk of these serious diseases developing, so maybe

a few fillings might not be so bad after all !

The next part of the digestive tract, the oesophagus, is a difficult

place for bacteria to gain a foothold. Here, microbe-laden food and saliva

are in rapid transit to the stomach: there's little time to eye up, choose

and settle down in an oesophageal site. Those that manage to colonise

this area, such as lactobacilli, can do so only transiently as the oesophageal

contents are continuously propelled into the stomach when we swallow.

Heading south from the oesophagus, microbes approach the acid pit of

the stomach. In here, food is processed for around three hours, giving

microbes plenty of time to attach themselves to the stomach walls. The

gastric juices secreted to liquefy food into chime and start the breakdown

of protein, are five times more acidic than lemon juice. So, splashed

into your face, lemon juice might cost you a few tears, but stomach acid

could cost you your sight. Yet for some, the stomach is a welcome sight

for sore eyes - Helicobacter pylori, for example, is very at home here.

HELICOBACTER PYLORI

In 1982, a truly dedicated microbiologist called Barry Marshall drank

some live H.pylori. The experiment made Barry very ill, and his wife very

angry, but it proved his theory that the bacterium causes gastric ulcers,

and H.pylori is now also thought to play a role in the development of

gastric and duodenal cancers. But Helicobacter is found in the stomachs

of 50% of people, yet only about one fifth of them become unwell, demonstrating

that lifestyle factors must also play a role in the development of disease.

Indeed, researchers now suspect that under some circumstances an H.pylori

presence in the stomach might be quite helpful since the bug seems to

protect against infant diarrhoea, and oesophageal disease.

Aside from H.pylori, the stomach houses lactic acid-producing bacteria

that include strains of Streptococcus and Lactobacillus. These microbes

convert sugar into acid. Some research suggests that lactobacilli can

inhibit the growth of H.pylori and decrease enzyme activity needed for

its survival in the acid environment. Lactic acid-producing bacteria of

the stomach do not require oxygen to survive: they are anaerobic. However,

unlike most anaerobic bacteria, certain strains can tolerate oxygenated

environments. The stomach is a well-oxygenated area because air swallowed

with food arrives here within moments of ingestion. So some lactic acid-producing

bacteria grow well here alongside bacteria that need to use the available

oxygen.

Most bugs do not relish the harsh conditions of the stomach, and alot

will dissolve as they succumb to acid attack. The tough ones drawn to

the intestinal habitats beyond must have intrinsic resistance to acid,

or a way to bypass the problem, for example under a protective blanket

of alkaline milk.

In the maze of the gastrointestinal tract, the small intestine follows

the stomach. Food moves through here in about four hours. Substances released

from the liver and pancreas help to breakdown food into its constituent

molecules. Digestion and absorption of these molecules occur across an

enormous surface provided by microvilli, hair-like projections covering

the surface of the small intestine.

The first part of the small intestine, called the duodenum, is only slightly

less acidic than the neighbouring stomach. However, the availability of

oxygen is much reduced due to consumption by bacteria living higher up

in the digestive tract. Therefore, this environment is ideal for bugs

able to resist acid in the stomach and which are indifferent to the presence

of oxygen. Microbes encounter decreasingly acid conditions as they descend

through the jejunum and then the ileum of the small intestine. And, from

the end of this section of the small intestine, oxygen availability also

decreases. The last part of the gastrointestinal tract, the large intestine

or colon, is virtually devoid of oxygen.

The main bacterial residents at the relatively acidic top end of the

small intestine are Lactobacillus and Enterococcus faecalis. Towards the

bottom of this section, where the living conditions are less arduous,

less acidic, and more appealing to a wider section of the bacterial community,

Lactobacillus and E.faecalis are joined by other bugs such as E. coli,

and Bacteroides.

COLONIC FLORA

By the time food reaches the colon, the body's work is almost over: the

arsenal of digestion and nutrient-harnessing mechanisms has been spent.

The remaining task for the large intestine is to remove the excess water

from what's left of the food, or faeces. The transit time through the

colon is normally a leisurely 12 to 24 hours. A longer stay in the colon,

or dehydration, will impact the faeces, both metaphysically and physically,

as more water is removed. Conversely, shorter colonic passage durations,

the result of excessive prune consumption or gut-damaging infections for

instance, will produce loose stools, or diarrhoea.

The sedate pace in the colon makes it a great place for bugs to fester.

In fact, it has so much 'hangout-potential' that bacteria reach levels

of over 1000 per millilitre of faeces. The flora in this part of the digestive

system include Enterococci, Clostridia and Lactobacilli, but by far the

most abundant species are Bacteroides and the oxygen-intolerant lactic

acid-producing Bifidobacterium. Thankfully the good bugs outnumber potential

villains like E.coli by as much as ten thousand to one.

POTENTIAL PROBIOTIC THERAPIES

Diarrhoeal diseases are common, particularly amongst children, and in

developing countries they are a major cause of death - estimates suggest

that a child somewhere in the world dies every 15 seconds from a diarrhoeal

disease. Promisingly, though, recent research indicates that one strain

of Lactobacillus, given in capsule or milk form, can help to treat childhood

diarrhoea.

Probiotics like these could also help in the treatment of inflammatory

bowel conditions like Crohn's disease. A cocktail of probiotic bacteria,

including strains of Lactobacillus, Bifidobacterium and Streptococcus,

has been proven to provide symptomatic relief for some sufferers.

Figure 4: Strains of Lactobacillus and Bifidobacterium are known to reduce the risk of cancer partly by reducing levels of cancer-causing substances.

But the potential clinical uses of probiotics are not limited just to

these conditions. Bacteria such as Lactobacillus and Bifidobacterium may

also turn out to be useful tools in the fight against cancers because

they have been shown to reduce the levels of cancer-causing substances

in the gut. Lactobacillus casei Shirota is one such strain and is present

in a well-known Japanese milk-based probiotic drink that is stored in

the fridges of approximately 26 million people worldwide (but, sadly,

not in mine because I don't like the taste- a shame, given its obvious

potential).

As well as cancers, allergic conditions may be prevented by the use of

probiotics. When given to pregnant women and then to their infants in

the first weeks of life, certain Lactobacillus strains can also reduce

the risk of allergy in the newborn.

Probiotics could also represent a cheap alternative to anti-HIV drugs.

Probiotic strains of Lactobacillus taken by mouth have been shown to colonise

the large intestine, and then to transfer from the rectum to the vagina.

Here they are able to modify the vaginal flora to reduce the chances of

HIV infection.

Historically, bacteria-laden fermented milk was used to help heal wounds

and fight infections. Today, a surgical patient's only likely exposure

to this substance is through his cup of NHS tea, but it seems our predecessors

may have been wiser then we think. When instilled in the gut flora, one

particular strain of Lactobacillus has been shown to reduce infection

rates amongst abdominal surgery patients.

Doctors are now unearthing mounting evidence for beneficial effects of

probiotic use amongst ill people, but there is very little research-based

evidence for the benefits of commercially-available products when used

by healthy individuals. With no legislation enforcing the proper identification,

documentation, and manufacture of over-the-counter probiotics, consumers

are currently clueless about the numbers and activities of the bugs they

are swallowing. Misleading marketing leads people to believe that live

Lactobacillus acidophilus cultures in some yoghurts confer health benefits

- but not all strains of this bacterium are probiotic. Perhaps when we're

better informed, our whetted appetites will create a strong market for

a range of bug-packed foods and supplements.

So, who knows? 'Special K with freeze-dried berries and lactobacilli'

may soon be on the shelves of a supermarket near you. I'll stick with

my plain, prebiotic (click here for the definition

of prebiotic) oatmeal though I think...or should I? I feel healthy;

I don't have the irritable bowel that seems to trouble every man and his

dog these days. But how healthy is my gut?

Our stone age ancestors had a diet brimming with bacteria. With 'Tesco's

Finest' still a long way off, our forefathers had to settle for what

they could forage. Food was usually stored in soil and eaten raw or fermented,

introducing billions of bugs with every meal. Plants were particularly

abundant and stone age people consumed over ten times as many varieties

as we do these days. Consequently, their varied diet allowed them to nurture

a gut flora far richer than we manage to sustain today on a diet of chips

and chocolate, bringing with it increased protection from allergies and

infections, problems that are becoming increasingly common in our sterility-obsessed

modern society.

Over the last hundred years or so, we have accumulated knowledge of the

possible dangers of microbially contaminated foodstuffs which has unfortunately

cultured an extreme fear of germs, and a predilection for chic chrome

kitchens and Smeg fridges. Funny then, that we now fill our Smegs with

little bottles of the very things they were originally designed to keep

out...

GLOSSARY

1 - Live microorganisms which, when administered in adequate amounts,

confer a health benefit on the host are known as probiotics.

2 - Substances ingested to promote the growth of probiotic microbes are

called prebiotics.

 

- December 2005