Monday, June 25, 2012

How bacteria break down human food

Last weeks post on the changing composition of bacteria in the vagina generated a lot of interest, and as there?s been quite a of talk about the human microbiome (all the bacteria that live on the human body) at the moment I thought I?d stick with the theme. This weeks post is about how bacteria break down the nutrients that humans eat and use them to create their own food.

The paper (reference 1 below) from PLoS One focuses on carbohydrates. Starting with some biochemistry background: carbohydrates are molecules made exclusively from carbon, hydrogen and oxygen (hence the name). These three molecules are arranged into a ring structure for the simple carbohydrates such as glucose, and those rings are put together into long complex branching chains for the complex carbohydrates such as starch and cellulose.

The ring structure of glucose, from wikimedia commons. Every bend or junction in the line represents a carbon molecule - organic chemists tend not to label the carbons as they make the picture messy.

Simple carbohydrates, like the glucose shown in the picture above, are fairly easy to metabolise and can be used to power-up ATP (the molecules that the cell uses for energy) or in the synthesis of proteins. More complex carbohydrates like starch or cellulose (shown below) take a bit more effort, as they need to be broken down into their component simple sugars before they can be processed. To break them down bacteria use a specific group of enzymes called CAZymes which stands for??Carbohydrate-active enzymes?. As enzymes are very specialised in the molecules that they break down, different CAZymes exist for different complex carbohydrates.

The structure of cellulose, from wikimedia commons. Although at first glance it looks very complex, notice that it is built up from the simple-sugar units shown in the picture above.

Different bacteria will have different CAZymes, but an?intriguing?question the PLoS paper set out to answer is how the pattern of CAZymes changes throughout the body. There isn?t just one bacterial species inside you, but many, each species differently related to the ones surrounding it. It?s less a community of bacteria inside you and more like a badly organised safari park, with different species all milling around in close proximity to each other, relying on the resources available in whichever part of the body they happen to live in.

The researchers compared the carbohydrate digesting abilities of 493 bacterial genomes, associated with five different sites on the exterior and interior of the human body. When they tried to work out the number and distribution of CAZymes by species they very quickly ran into difficulties. Some bacterial families, such as?Bacillaceae, had an average of number of 25 sugar-cleaving enzymes, with a?respectable?standard deviation of 3.3 (for the uninitiated, the standard deviation measures how likely each individual is to be close to the average). The bacterial family?Clostridiaceae on the other hand had an average of 56 sugar-cleaving enzymes but with a standard deviation of 79! As well as showing the large inter-species variation, this also makes it difficult to predict relatedness between bacteria based on their carbohydrate-digesting abilities.

As comparing species didn?t seem to be yielding particularly concise results, the researchers then moved onto comparing CAZymes by bacterial habitat. Unlike humans, and indeed pretty much all eukaryotes, bacteria don?t just pass genes down to their offspring, they can also pass genes across to a nearby friend. Unsurprisingly, bacteria living in the same place on the body tended to have more similar carbohydrate-digesting enzymes than bacteria that were more related by species. Overall the researchers found four major patterns of carbohydrate-use:

1) Bacteria in the nose and?nasal?cavities - unsurprisingly these bacteria tended to have very little carbohydrate metabolising ability (very few people inhale starch)

2) Bacteria in the vagina ? These bacteria tended to be breaking down more simple sugars, and also had carbohydrate forming enzymes in order to build up biofilms

3) Bacteria in the mouth ? these bacteria have a wide range of carbohydrate digesting enzymes in order to break down the bits of food which get trapped in your teeth. The researchers also identified three enzymes used for metabolising dextran, which may be unique for mouth-bacteria and seemed to be a marker for plaque formation.

4) Bacteria in the gut ? this is where the big carbohydrate-digesting muscle lies! Not only do gut bacteria have plenty of CAZymes for human carbohydrates, they also have range that deal with plant carbohydrates. Many of these bacteria have the ability to form a cellulosome ? a large complex of cellulose digesting enzymes all held together by scaffold proteins.

It may be slightly weird to think of bacteria living in so many parts of your body ? colonising your spaces and eating your food ? but really, it would have been much more of a surprise to find they weren?t. Pretty much every surface on earth has bacteria living on it, and humans are such a warm, moist, nutrient-rich surface that they provide a great living environment for a huge number of bacterial species.

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Cantarel BL, Lombard V, & Henrissat B (2012). Complex carbohydrate utilization by the healthy human microbiome. PloS one, 7 (6) PMID: 22719820

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