Bacteria of human intestinal tract
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Jane Hurd
Bacteria of human intestinal tract

The Mucus-Lover that Stops Mice from Getting Fat

When Bob Paine chucked starfish into the Pacific Ocean in 1963, he was also throwing bombs into the heart of ecology. Back then, the prevailing view was that communities of animals and plants were fairly stable, provided that they contained a diverse set of members. But Paine showed that some species are disproportionately influential. Take the ochre starfish. When Paine prised them from a stretch of Washington shore and pitched them into the surf, the mussels that the starfish ate advanced over the shore like a black glacier. They crowded out other creatures and radically remodelled the coastline.

Paine described crucial species like the starfish as “keystones”, after the central stone that stops an arch from collapsing. The whole community matters but some species are particularly important. Or to borrow from Orwell, “All animals are equal, but some animals are more equal than others”.

Now, the same lessons are being learnt in an ecosystem that’s very different to the rocky Pacific coast—the intestine. The guts of humans and other mammals contain thriving trillions of bacteria and other microbes. This “microbiota” outnumbers the cells that make up our actual bodies. They are so numerous that they are usually studied en masse. Scientists collect samples—say, from faeces—and sequence all the DNA within them, piecing together the identities of the resident species and families.

It’s a powerful approach, which has already taught us much about our gut passengers. Studies have show how these communities change as we get grow older, eat different diets, or take courses of antibiotics. Unsavoury but impressive studies have shown that people can be cured of life-threatening gut infections by being implanted with someone else’s faeces. And many scientists have found links between our gut bacteria and obesity.

For example, in 2007, Ruth Ley, Peter Turnbaugh and Jeffrey Gordon showed that a group of bacteria called the Bacteroidetes are rarer in the guts of obese mice and humans, while a rival group—the Firmicutes—are more common. And a few months ago, Turnbaugh and Lee Kaplan showed that gastric bypass surgery (at least, in mice) might lead to weight loss because it changes an individual’s gut microbe society. Antibiotics might lead to obesity by creating similar upheavals.

The whole community matters but, again, some species are particularly important. One of these Very Important Prokaryotes is called Akkermansia muciniphila. Willem de Vos from Waginingen University first discovered it in 2004 but humans have been carrying it for much longer. Akkermansia accounts for 3 to 5 percent of the bacteria in a normal gut, making it one of our more common intestinal microbes. And it seems to wield a strong influence on our body weight.

Amandine Everard and Patrice Cani from the Catholic University of Louvain have been working with de Vos to understand how this microbe gives its host the guts to stave off the pounds.

They found that Akkermansia is 3,300 times less common in the guts of mice that are genetically predisposed to being obese than in normal rodents. Also, its numbers fall by 100 times when any mouse eats a high-fat diet. This mirrors the results of surveys in humans—if people have lots of Akkermansia in their guts, they tend to be slimmer.

But boost the microbe’s faltering numbers, and you can reverse several of the problems associated with obesity. When team fed their mice with a dose of Akkermansia, they put on less weight and body fat after eating a high-fat diet. They also showed fewer signs of type 2 diabetes. For example, their climbing levels of sugar in their blood completely reversed, and they became less resistant to insulin—the hormone that controls blood sugar.

When the team fed their mice with dead bacteria, nothing happened, proving that the bacteria need to be alive to exert their weight-controlling influence. They don’t, however, need any help. Everard found that a high-fat diet changes the entire community of bacteria in a mouse’s gut, but the addition of Akkermansia doesn’t. Whatever it does, it does it by itself. The whole community matters but some species are particularly important.

Akkermansia feeds upon the delectable mucus that covers our intestines—its species name, muciniphila, is Latin for “mucus lover”. This mucus comes in two layers. The inner one is a barrier that keeps harmful microbes out. The outer one is a meeting room, where our cells parlay with helpful species like Akkermansia.

As mice gain weight, their mucus layer gets thinner, but Akkermansia seems to prevent this erosion. By shoring up the mucus, it could prevent other microbes from inflaming the gut and triggering other changes that cause disease. And there’s probably more. Everard’s team also found evidence that Akkermansia could also affect the division of its host’s gut cells. It also persuades its host to release molecules that kill competing bacteria and reduce inflammation.

Cani sees the relationship between the microbe and its host as a mutually beneficial one. “The host provides energy and a habitat to Akkermansia and, in turn, Akkermansia protects its host from invading microbes.”

Akkermansia might eventually help us to control our weight or reduce the risk of diabetes, but that will take a lot more research. This study was done in mice, and Cani wants to check that the same relationships happen in the human gut. But since this microbe actually lives inside the mucus layer, it has a lot more potential for affecting our bodies than a lot of other “probiotics”. Indeed, when Everard’s team repeated their experiments with Lactobacillus plantarum—a “helpful” microbe commonly used in probiotic foods—it did nothing for the fat mice.

This is a reminder that our gut bacteria are not stowaways. They’re an intimate part of our lives. They contribute to the huge network of proteins and hormones that controls how hungry we get when we don’t eat or how full we feel when we do. They affect how much fat we store and how much sugar builds up in our blood. They influence our immune system, and how we decide which microbes to tolerate and which to attack.

We’re only starting to understand the conversations that happen between our guts and the microbes within them. And we’re only starting to identify the most important species among the vast hordes—the gut equivalents of Paine’s starfish. Rob Knight from the University of Boulder in Colorado, who studies the microbiota, thinks that research in the future will “likely shift back and forth between studies of individual microbes, like this one, and whole-community studies that allow us to generate hypotheses about which other key players in the gut they interact with.”

Reference: Everard, Belzer, Geurts, Ouwerkerk, Druart, Bindels, Guiot, Derrien, Muccioli, Delzenne, de Vos & Cani. 2013. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity.

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