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