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Saturday, July 23, 2011

Living in symbiosis

Anyone who's ever managed a multi-person project - or managed a kids' art project, for that matter - knows how hard it is to keep everyone working together in harmony. In the best case scenario, everyone's efforts benefit everyone else. But more likely, something will offset the balance and leave at least one person feeling alienated and bitter.

Maybe we should take a lesson from our microbes: in the majority of cases, the intestinal bacteria manage to exist in a nice symbiotic relationship with the human body that houses them. It can't be an easy task for all those cells (and we're talking trillions of bacterial cells) to operate in such close contact with their (comparatively) giant host. Yet they do - their project of "living in symbiosis" usually goes off without a hitch.

"Symbiosis". Photobucket image by GlynGPKSS 

How do the microbes achieve that symbiosis so successfully?

This was the question explored by a team of Harvard researchers under the direction of Dr. Wendy Garrett, an immunology professor and oncologist. Their 2011 paper is entitled Host and gut microbiota symbiotic factors: lessons from inflammatory bowel disease and successful symbionts.

The researchers at the Garrett lab happen to know a lot about Inflammatory Bowel Diseases (IBDs) possible examples of what can happen when a host and its bacteria fail to maintain symbiosis. So, more than anyone, these researchers know about the challenges faced by the host-bacteria relationship: the foods that enter the body (since fried beef takes a different toll on the microbes than lentil soup), the functioning of the immune system, and the number of pathogenic bacteria that are competing for space in the gut. All these things have the capacity to work against symbiosis.

The study reads like one of those workplace "let's identify our strengths" exercises. First, it explored what features of the host (i.e. the human body) contribute to symbiosis. Then, it covered the contributions of the bacteria themselves.

When it came to the body, the researchers picked out several genes that they felt were necessary for coexistence with gut bacteria. According to previous experiments, these genes affect the immune system and thus affect what bacteria colonize the gut. Meanwhile, the researchers identified three genera of bacteria that seemed especially good at living in symbiosis: Bacteroides, Helicobacter and Lactobacillus. The bacteria's list of workplace strengths included the ability to stick to mucosal surfaces inside the intestine, a tolerance for extreme pH shifts in the gut, and a propensity for lowering inflammatory processes in the body.

This makes for a nice, tidy presentation of what it takes to live in symbiosis: the right genes and the right environment. Possessing certain genes may make it easier for bacteria to get along with you. And the specific bacteria that you have encountered in your daily comings and goings may do their part to keep the relationship in harmony.

This is part of an exciting new research path - and it's about more than just IBD prevention. The Garrett lab is exploring the overall relationship between gut bacteria and the immune system - how disruptions in the community of gut bacteria may contribute to the body's inflammation responses, and how that inflammation might lead to disease or cancer.
Ballal SA, Gallini CA, Segata N, Huttenhower C, & Garrett WS (2011). Host and gut microbiota symbiotic factors: lessons from inflammatory bowel disease and successful symbionts. Cellular microbiology, 13 (4), 508-17 PMID: 21314883

Monday, June 27, 2011

The connection between gut bacteria and restless legs syndrome

Some people's legs have a mind of their own. Their legs decide that they need to pace the room constantly instead of sitting. Their legs are responsible for the twisted knot of sheets at the end of the bed every morning. Their legs burn or tingle or get creepy-crawly sensations, especially when they try to sit down and relax.

Legs picture by Pedro Simões, via Flickr

Restless legs syndrome (RLS) is associated with an irresistible urge to move the legs. As you can imagine, this brings its own set of problems. A lot of the time, people with RLS have trouble getting to sleep or staying asleep - making them grouchy and unfocused in the daytime. The sensory and motor abnormalities in this syndrome have a neurological connection, but so far there is no clear answer about how to make restless legs go away.

According to one intriguing new study in Sleep Medicine, restless legs syndrome may be another thing connected to gut bacteria gone haywire.

The study came about because its investigators, Weinstock and Walters, had previously noticed that many people with celiac disease and Crohn's disease happened to have a diagnosis of restless legs syndrome.

They wondered: Does the reverse relationship hold between gastrointestinal problems and restless legs? That is, if we take a group of people with known RLS, would we find that they have more gastrointestinal problems than people with normal leg movement?

The gastrointestinal problems they were interested in studying were irritable bowel syndrome (IBS) and small intestinal bacterial overgrowth (SIBO).

Importantly, IBS is a "functional syndrome". That means doctors diagnose it based on reported symptoms rather than a specific test that confirms or disconfirms it. So to be fair, there's no guarantee that people with IBS have anything wrong with their gut bacteria. But in recent years IBS has been linked to SIBO, a condition that is definitely associated with too many bacteria hanging out in a neighborhood where they don't belong: the small intestine.

SIBO itself is diagnosed via an indirect method called the "lactulose breath test". The attraction of this method is that it involves nothing more invasive than drinking a cup of sugar solution and blowing into a plastic tube.

The researchers wanted to investigate both IBS and SIBO because each one indicates that something is going wrong with digestion; some patients have both problems, but others have just one or the other. They ended up with one measure of gastrointestinal distress that was based on reported criteria (i.e. IBS), and one that was based on measurable biology (i.e. SIBO).

People with restless legs syndrome discovered the study through ads that made no mention of gastrointestinal symptoms. Their diagnoses of RLS were confirmed by the investigators, and then each subject was assessed for both IBS and SIBO.

It turned out that IBS was diagnosed in 28% of subjects with restless legs syndrome, compared to 4% of the controls. In some of the cases, the IBS symptoms had appeared before the onset of the RLS symptoms. In others, the two problems started around the same time.

As for SIBO, the breath test showed it was present in 69% of the people with restless legs syndrome, compared to 28% of the controls.

The conclusion? People with restless legs syndrome have a greater incidence of IBS and SIBO - that is, a greater incidence of problems in the digestive system - than people without it. And in at least some people with restless legs syndrome, the associated gastrointestinal problem was related to bacterial overgrowth in the small intestine.

The research is far from concluding that gastrointestinal problems CAUSE restless legs or vice versa. But the researchers did confirm co-occurrence, and they also put forward the idea that there may be a common mechanism that leads to both: maybe some kind of inflammatory process in the body that leads to central or peripheral nerve damage, or a change in micronutrient absorption, resulting in restless legs.

In support of this, the researchers did an informal review of conditions that tended to co-occur with RLS; 89% of these disorders had been associated with inflammation or immune system activation.

In turn, the connection between inflammation and alterations in gut microbiota has strong support in the literature. But that's a topic for another day.

Lots of questions remain about restless legs syndrome, but the connection that this study made between restless legs and gut troubles seems to confirm certain clinical observations. We need more information though - let's hope this area of research stays alive and... kicking.
Weinstock LB, & Walters AS (2011). Restless legs syndrome is associated with irritable bowel syndrome and small intestinal bacterial overgrowth. Sleep medicine, 12 (6), 610-3 PMID: 21570907