Tuesday, January 8, 2013

...And The Meek Shall Inherit Our Bodies?

Image credit:  iStockphoto/Sebastian Kaulitzki (obtained from Science Daily)

Cell for cell, your body isn't your own- your cells are vastly outnumbered by the bacterial cells living inside of you. Their 3.3 million genes outnumber your modest 23,000, and at least 2-5 pounds of your body weight is actually bacterial biomass. Your health, moreover, is in large part dependent on their presence- for better or worse.

Whether we realize it or not, the masses of tiny microbes which call our bodies 'home' are a large part of our lives. It is easy to forget about our microscopic companions- we can't see or feel them, after all- and so it isn't until they start acting up that they make their presence known.  For this reason, bacteria have historically gotten a bad rap. Often vilified for their pathogenic qualities, the general public takes great care to prevent contamination through the widespread use of antibiotic soaps and hand sanitizers. It would be impossible to get rid of all of the microscopic critters we carry, however, and chances are you wouldn't want to, anyway. Bacteria are an essential part of our everyday lives- they help us to digest our food, synthesize certain vitamins, and, in some cases, interact with our immune systems and protect us against disease.

Microbes have been established as such a vital and intimately associated part of of lives that we now have a word for the population of bacteria we are at this moment sheltering in our bodies, that humble abode- the microbiome. Microbiome refers to the collection of microbes housed in and on our bodies,  almost 100 trillion bacteria per person.

Preserving the delicate balance of bacteria within our microbiome appears to be important for our health and well-being. Alteration or imbalances within the microbiome have been linked to various diseases, most prominently inflammatory bowel disorders. Many doctors and scientists believe that understanding the microbiome may be of medical importance and perhaps aid in the treatment and diagnosis of diseases associated with changes in our microbiome. The percieved medical utility of our microbiome elicits visions of 'diagnostic' microbiome sequencing, with patients recieving personalized 'bacterial' treatments to return their microbiome to homeostasis.

It still remains to be seen, however, if such a baseline even exists. Everyone is different, and so are our microbiomes. The composition of the bacterial crowd we harbor varies by as much as 40-50% from one person to another. To get a representative sample of an individual's microbiome a sample from an area of interest is taken- or, when gut bacteria are being studied, a stool sample is obtained- and analyzed by sequencing.

It has been estimated that everyone carries approximately 140 different bacterial species (of the 1,000 different bacterial species which have been found in humans to date), and so one of the challenges of analyzing the microbiome is differentiating between the many bacterial species present. One of the most commonly used methods involves homing in on a particular gene coding for 16s rRNA. The product of this gene, 16s rRNA, is a component of the ribosome, or protein making machinery. Slight variations in 16s rRNA are used to distinguish between bacteria of a different genus and species. Known DNA sequences from the human genome are thrown out to avoid contamination of results by human DNA, and the remaining data are analyzed to identify bacterial species present in the sample.

Not only do most people carry unique combinations of bacterial populations, but different bacteria are also present in different proportions within our bodies. The composition of our microbiome is constantly in flux, as it is tied to a number of external and internal variables.

Diet is one such variable, and it seems to have a large influence on the composition and diversity of our gut microbiome. Eating certain foods, for example, encourages the growth of particular species of bacteria.  In one 2010 study, bacteria from the gut of healthy children from Burkina Faso were compared to bacteria found in the gut of healthy Italian children. The diet of the children from Burkina Faso was high in fiber and vegetables and low in fat, while the diet of Italian children tended to be higher in starches, sugars, and fats, and lower in fiber. The children from Burkina Faso, they found, had higher numbers of bacteria from the phylum Bacteroides and fewer from phylum Firmicutes; in the Italian children, however, the situation was reversed. It may not be a coincidence, then, that  leaner individuals tend to have more Bacteroides bacteria and less Firmicutes bacteria, while the proportions are often reversed in obese individuals. Similarly, the composition of gut bacteria was altered in participants of a recent study who were put on a high-fiber diet; it was noted that Faecalibacterium prausnitzii, a bacteria known for its anti inflammatory properties, also became more prevalent.

Reinforcing these earlier results, a study published in Nature found that certain saturated fats commonly associated with the 'Western diet' altered the mix of bacteria in the gut. One bacteria in particular, Bilophila wadsworthia, became over-represented in the gut of those who participated in the study. Increased levels of B. wadsworthia are often found in patients with appendicitis and IBD.  

Taken together, these findings illustrate the importance of diet and external factors in maintaining a healthy balance of gut bacteria. The dynamics of our microbiota, however, are not just the product of a single variable: as usual, the issue is far more complex. Stress can alter the bacterial composition of our microbiomes (it also works the other way around: the bacteria which populate our gut can also affect stress levels and brain chemistry). 

But there is no escaping the genetics factor, it seems: scientific evidence is increasingly supportive of a link between our genes and gut bacteria. Now, researchers are putting that idea to the test.

In a letter which appeared yesterday in the journal Gut, researchers at the Karolinska Institute and University of Glasgow used this idea as the basis of a "proof-of-concept" study analyzing gut bacteria and DNA variation at 30 different genes in 51 individuals. Each of the 30 genes included in the study are known to increase the risk of Crohn's disease, and so they set out to analyze whether there was a correlation between variants of each gene and the gut microbiome. They found that variation at the gene IRGM was associated with increased levels of Prevotella bacteria.

Admittedly, this result is not very telling- besides the suggestion that certain IRGM variants may encourage the dominance of Prevotella bacteria, it is hard to glean much information from this finding alone. It does, however, suggest that there may be something to the gene-bacteria link. Filling in the gaps in our understanding of how variation in our genomes may affect variation in our microbiomes, and the ways in which microbiome diversity is constrained by our genetics, may be the key to moving the study of the microbiome and its therapeutic potential forward.

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