Human gut bacteria linked to obesity

By Ed Yong | October 6, 2008 10:00 am


Blogging on Peer-Reviewed ResearchThere is a widespread belief, that being overweight or obese is a question of failing willpower, fuelled in no small part by food, fitness and beauty industries. But if we look at the issue of obesity through a scientific spyglass, a very different picture emerges. Genes, for example, exert a large influence on our tendency to become obese often by influencing behaviour – a case of nature via nurture. But it’s not just our own genes that are important.

713px-escherichiacoli_niaid.jpgIn terms of processing food, humans are hardly self-sufficient. Our guts are the home of trillions of bacteria that help to break down foodstuffs that our own cells cannot cope with. Together the genes expressed by these intestinal comrades outnumber our own by thousands of times, and yet we are still largely in the dark what they do.

Over 90% of these bacteria, collectively known as the microbiota, come from just two groups – the Bacteroidetes and the Firmicutes. Now, new research suggests that the proportion of these groups is linked to the risk of becoming obese.

Ruth Ley, Peter Turnbaugh, Jeffrey Gordon and colleagues at Washington University first noticed the link between the microbiota and obesity by studying a special strain of fat mice. These mice lack the hormone leptin, which controls the body’s ‘fat thermostat’. Without it, the mice cannot monitor the amount of fat in their body and quickly become obese through overeating.

fatmouse.jpgThe team noticed that these mice had 50% fewer Bacteroidetes and 50% more Firmicutes in their bowels than their lean counterparts. They saw the same thing in humans. The relative proportion of Bacteroidetes increased in obese people as they lost weight through low-fat or low-carbohydrate diets, while the Firmicutes became less abundant.

The link between the microbiota and obesity became even clearer when Gordon looked at a special strain of mice with no microbiota of their own. These intestinal tabula rasas proved to be strongly resistant to the fattening effects of unhealthy diets. After eight weeks on a 40% fat diet, these animals put on less than half as much weight as their normal peers, despite eating the same amount of food. When the team transplanted the microbiota from fat and lean mice into the germ-free strains, those colonised by microbiota from fat donors packed on far more weight than those paired with lean donors.

To find out why the shifting bacterial balances were affecting body weight, Gordon and co. compared the microbiota of fat and lean mice at a genetic level. Samples from fat mice showed much stronger activation of genes that coded for carbohydrate-destroying enzymes, which break down otherwise indigestible starches and sugars. As a result, these mice were extracting more energy from their food than their lean cousins.

The bacteria were also manipulating the animals’ own genes, triggering biochemical pathways that store fats in the liver and muscles, rather than metabolising them. While these effects are relatively small, Gordon believes that they can lead to very large fluctuations in weight, over the course of months or years.

Obviously, the microbiota are not the whole story behind the obesity epidemic. We now need to understand how they interact with other things that affect our risk of becoming obese, not least of all, our own genes. And there is much we still don’t know about our life-long passengers, such as how they sense and respond to their host’s condition, how they are passed on, or how they are affected by our diet. By answering these questions, scientists could then assess whether actively shifting our bacterial balances could help to stem the worldwide increase in obesity levels.

Reference: Ruth E. Ley, Peter J. Turnbaugh, Samuel Klein, Jeffrey I. Gordon (2006). Microbial ecology: Human gut microbes associated with obesity Nature, 444 (7122), 1022-1023 DOI: 10.1038/4441022a

Peter J. Turnbaugh, Ruth E. Ley, Michael A. Mahowald, Vincent Magrini, Elaine R. Mardis, Jeffrey I. Gordon (2006). An obesity-associated gut microbiome with increased capacity for energy harvest Nature, 444 (7122), 1027-131 DOI: 10.1038/nature05414

An introduction to the microbiome

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