Could 'friendly bacteria' hold the key to weight control?

Could 'friendly bacteria' hold the key to weight control?
By Jerome Burne
Published: 17 July 2007
Independent UK

A recent trial of probiotics as a treatment to help autistic children had to be stopped because it was so effective. Parents who had noticed significant improvements in the behaviour of their children refused to continue because they didn't want to be given the placebo when the treatments were swapped.

It was a professional disappointment for the microbiologist researcher, Professor Glen Gibson of Reading University, but yet another triumph for what are rapidly becoming known as the "friendly" gut bacteria.

They might soon be notching up even more impressive achievements: controlling weight gain, for example, or reducing stress.

The latest term for the dense ecology of the 500-plus species living in your gut is the "microbiome". It is a place that plays a key role in how we develop, from the moment we leave the womb.

Don't absorb nutrients from your food too well? Perhaps something went wrong at the time that bacteria were controlling the way the lining of your gastrointestinal tract develops. Suffer from hayfever? The microbio-me affects your risk of developing allergies by influencing the sensitivity of the immune system. Problems with stress? Right from the beginning, these bacteria were in there shaping the connections between the brain and the adrenal glands.

But what's really getting everyone excited is that certain species of bacteria almost certainly play a key role in putting on weight. Whether you are slim or straining at the waistband may be decided by how effectively two particular species of gut bacteria are working together. Encouraging the right combination could eventually be a revolutionary way of shedding the pounds.

The first clue about the link with weight came after observing rats that were put in a super-sterile environment from birth. With no bacteria around to colonise their guts, they had no microbiome. The result? The animals stored very little fat - 60 per cent less than usual - even though they ate voraciously. But allow bacteria in and they start to put on weight: after two weeks they weigh the same as normal.

Last summer a team headed by Professor Jeffrey Gordon at Washington University's Centre for Genome Sciences managed to narrow the strains responsible for the fat storage down to two key players: Bacteroides thetaiotaomicron (B. theta) and Methanobrevibacter smithii ( M. smithii). Rats with both strains had 13 per cent more body fat than those with only one. The possibility, some years away yet, is that researchers may discover how to manipulate your gut bacteria population so less fat gets stored.

But that's not the end of the tricks that B. theta has up its sleeve. It could be playing a role in our current diabetes epidemic, according to Dr Jeremy Nicholson of Imperial College London. "Overweight people are more likely to develop diabetes, but why?" Nicholson asks. "It's not really clear why being overweight should affect your blood sugar control. "

The clue, he suggests, is that B. theta also affects the regulation of a set of proteins known as PPARy, which are found in fat cells. PPARys are involved in insulin control - in fact they are targeted by a new class of diabetes drugs. "Maybe the recent massive rise in diabetes is the result of changes to the metabolites produced by B. theta," he says.

Human beings are actually more bacteria than human: in fact, 90 per cent of the cells in your body are bacterial. And the microbiome is a world we've only just begun to explore. We probably know rather more about the bottom of the ocean than the flora and fauna of our insides.

But the potential to harness bacteria for our benefit seems ample. Even commercially available probiotic preparations, which contain four or five different strains at most, have been shown to help with everything from autism to allergies to irritable bowel syndrome. Several studies have shown that newborn babies at a high risk of inheriting eczema were much less likely to develop it if the mother took probiotics in the weeks before birth and if the child did soon after. Few people know that Adolf Hitler was reportedly one of the first patients to use probiotics to improve their eczema. And experts believe that it will soon be possible to be far more precise - to target specific strains for specific disorders.

A glimpse of this probiotic future came last year with a paper describing how genetically modified probiotics were able to put five out of 10 patients with severe Crohn's disease into remission. Professor Lothar Steidler, of the Alimentary Pharmabiotic Centre at University College in Cork, changed the genes in Lactococcus lactis (L. lactis) so that it produced a natural anti-inflammatory chemical, interleukin 10 (IL10), once it arrived in the gut. IL10 is already used as a drug treatment for Crohn's disease, but it is very expensive and has unpleasant side effects. Using a modified L. lactis as the delivery vehicle meant that only a tiny fraction of the amount taken in the drug form was needed; the side effects were minimal.

So if gut bacteria are so vital, why are we so free with antibiotics? It could be this that accounts for the hyperactive immune response that characterises allergies. "We don't just have bacteria in our guts, we also have fungi there," notes Professor Gary Huffnagle of the medical school at the University of Michigan. "When the bacteria get knocked out by antibiotics that allows the fungi to spread."

That is bad because it's the gut bacteria that affect the allergic response. "Normally they damp it down but when certain fungi get the upper hand they trigger a hyperactive response," Huffnagle says.

A true view of our inner bacteria can be extremely humbling. "The average human should be regarded as a complex ecology rather than as an individual," Professor Nicholson says.

"Indeed, it is tempting to suggest that the role of the host is to function as an advanced fermenter, carefully designed to maximise the productivity of the microbiome."