Gut feelings: EDs and the microbiome

Consider this thought experiment:

Drop a person in a blender (since it's all hypothetical, go ahead and make it someone you don't like. Feel better? I bet you do!). Then, count all the total number of cells that are produced. Only one in ten of these cells will be human. The other 90%? Those are all microbes. If you look at the total number of genes in your human smoothie (NOT coming soon to a Jamba Juice near you), the numbers are even more skewed: only one in 100 genes are human. The rest are, again, bacterial. The total collection of all of these bacteria living in and on our bodies is known as the microbiome.

The idea isn't to gross out the card-carrying germophobes among us. But let's face it: we're just as much bacterial as we are human. Plenty of these microbes live on our skin, in our lungs and genital tracts. The mother lode of microbes, however, live in our gut. They are crucial to extracting energy from food, and these microbes are extremely sensitive to what we eat. Starving mice for just one day dramatically alters the composition of their gut microbes. Specifically, it decreases a type of bacteria known as Firmicutes. When researchers transplanted Firmicutes into the guts of lean mice, they rapidly gained weight (Crawford et al., 2009)

When it comes to eating disorders, there isn't much talk of microbes. There are the occasional papers from researchers like Sergei Fetissov about potential auto-immune responses in people with eating disorders, and some work on PANS (pediatric auto-immune neuropsychiatric syndrome) and anorexia, but generally, researchers haven't looked at the role of the microbiome in triggering or perpetuating an eating disorder.

Much work has been done in obesity research. Scientists have consistently found that people with a BMI >30 have different gut microbes than people with BMIs in the "normal" range. As well, bariatric surgery also significantly changes gut microbes as people lose weight, making them look more similar to the bacterial profiles seen in "normal weight" individuals. A more recent study in The ISME Journal proposed a microbiome diet: eating foods that would eliminate a type of bacteria called Enterobacter helped a person lose drastic amounts of weight in a short period of time (Fei & Zhao, 2012).

So how are microbes involved in eating disorders? No one really knows. Cindy Bulik has begun a study looking at this relationship, but the results still aren't in. Based on the studies above, it's reasonable to assume that ED behaviors (starving, binge eating, and/or purging) will have a significant effect on a person's microbiota. It still has to be measured, but I would bet a lot of money on it. The question is what do these microbial changes have to do with ED symptoms?

Imbalances in gut microbes in mice and rats have been found to alter patterns of risk-taking and anxious behaviors--something that also happens in people with EDs. They could also, perhaps, explain weight loss seen in anorexia and EDNOS. Maybe the initial restricting triggered a significant change in gut microbes that amplified the effects of malnutrition. Maybe they lacked a group of microbes that produced an important hormone regulating hunger and satiety. No one really knows.

One hint to the potential role of microbes in EDs comes from a study published today in the journal Science (Smith et al., 2013). The scientists studied the relationship between gut microbes and kwashiorkor, a form of severe malnutrition that occurs when a person doesn't eat enough protein. Of the 317 twin pairs from Malawi that the researchers followed for three years, half became significantly malnourished and 7% developed signs of kwashiorkor. Obviously, a lack of protein is crucial to the development of this disease but it's not the only factor as not everyone with a severely protein-deficient diet will develop kwashiorkor. Something else had to be going on.

First, the researchers treated twin pairs discordant for kwashiorkor (that is, one twin had it, whereas the other didn't) with "ready-to-use therapeutic food"- basically peanut butter on steroids. Twins with kwashiorkor had significantly different from nearby twins who (presumably) at pretty close to the same diet. The researchers found significant changes to the gut microbes in the ill children with the use therapeutic food. Discontinuing the therapeutic food caused a regression in the functioning of the gut microbes.

The kicker is this: when the researchers fed mice a standard Malawian diet and inoculated them with microbes from the guts of malnourished children, they rapidly lost weight and also developed kwashiorkor. This happened despite the fact that their diets contained adequate calories. One of the reasons that the researchers believed the therapeutic food is so effective at treating kwashiorkor is that it helped restore normal gut microbes.

To say what effect restoring normal gut flora will have on ED symptoms remains to be seen. Probiotics are a hot item, but much of the research is fairly overblown. There's definitely still potential there, and we need to know more about which populations of people are likely to benefit and which aren't. But it's an interesting idea, and I think we need to know a lot more about the role of the microbiome in the development and perpetuation of EDs.

In closing, a quote from scientist John Rawls in an interview with Scientific American:

“We are in the midst of a revolution of our ability to describe the composition and physiological potential of these bacterial communities...What we can begin to speculate on, though, are the different types of relationships that might be taking place. We know gut microbiota enhance our ability to extract calories from complex carbohydrates, which is clearly a mutually beneficial relationship. But it’s thought that all vertebrates have the capacity to digest and absorb other types of nutrients, such as lipids, proteins and simple carbohydrates, so it’s not readily clear how we could enter into a mutually beneficial relationship with bacteria with regard to those nutrients."

13 comments:

hm said...

GREAT post. What a thought. There is so much more under the surface of an ED to be considered.

I know I have a much more sensitive gut than many people. I get stomach discomfort easily- not just the usual refeeding bloating and awful "full" feelings- but red meats, sugar, oils, all kinds of things also give me the shits and make me feel like I'm coming down with the flu. I know these things didn't used to bother me like they do now, so I'm betting my ed has done some damage to my intestinal flora and therefore my digestive capabilities. It sucks.

I guess the real question is, is there a way to fix that. I do take probiotics and digestive enzymes daily and can feel it if I forget to do so. It does help.

Tetyana said...

"Probiotics are a hot item, but much of the research is fairly overblown." Thank you! (And add to that antioxidants, I love that awesome Cochrane review that put a stop to that (for those who read it, of course)).

I'm interested to see the results of this future research. It is a cool area I know very little about. That's for the post Carrie.

Colleen said...

I think this is fascinating!

Two years ago that Julie O'Toole blogged about gut flora and obesity:
http://www.kartiniclinic.com/blog/post/some-weird-things-about-fat-obesity/

This is where I was introduced to the idea of gut microflora. I particularly liked the link to the NY Times story:
http://www.nytimes.com/2006/08/13/magazine/13obesity.html?pagewanted=1&_r=0

Of course the focus is likely to be on obesity because, you know, that's an epidemic. But maybe it will help shed light on EDs as well. Exciting, paradigm-busting stuff!

CHARLOTTE'S RANT said...

You so rock, my friend.

IrishUp said...

kewl-kitty!

This reminds me of another symbiotic relationship; micorrhizae and plants. Micorrhizae are fungi [INSERT ALL THE JOKES HERE] that expand the surface area of plant root systems, facilitating increased absorption of nutrients. In exchange, since eukaryots don't produce their own food, they pilfer sugars from the plant.

Altering soil conditions alters the micorrhizae species distributions, which in turn directly affects what plants can and cannot grow. Micorrhizae are incredibly dependent upon micro-habitat conditions; work I did as an undergrad showed that species distributions of the m.s on dune grasses varied systematically just between the front (ocean side), tops, and backs of the same dune formation.

So some work has been done seeing if whether replenishing native m. species in impoverished or impacted soils can help reestablish lost or failing indigenous species. The answer seems to be "yes, BUT". In the absence of other ameliorating factors, repopulation alone will not work in the long run, because whatever caused the initial shift, will eventually cause it again.

Carrie Arnold said...

Tetyana,

Here's an article about the myths of antioxidants. http://www.scientificamerican.com/article.cfm?id=is-free-radical-theory-of-aging-dead

The whole thing used to be free, but SciAm since paywalled it. Hopefully your university subscribes or you can get a copy. It's really interesting.

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rs gold said...

I know I own a far more hypersensitive intestine when compared with a lot of people. I purchase abdomen soreness easily- not only the typical refeeding trapped wind and bad "full" feelings- nevertheless red beef, sugars, natural skin oils, everything furthermore give me the shits and make me feel as if Now i'm decreasing together with the influenzabuy runescape gold.

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I'm a science writer, a jewelry design artist, a bookworm, a complete geek, and mom to a wonderful kitty. I am also recovering from a decade-plus battle with anorexia nervosa. I believe that complete recovery is possible, and that the first step along that path is full nutrition.

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nour·ish: (v); to sustain with food or nutriment; supply with what is necessary for life, health, and growth; to cherish, foster, keep alive; to strengthen, build up, or promote



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