The Friends And Foes In Our Gut: A Guide To The Microbiome

The microbiome refers to all the microbes (and their genes) found on and inside our body. We are teeming with bacteria and other microbes. We are actually outnumbered by microbes; most estimates conclude that for every 1 of our own cells there are 3 microbes in our body. The question that naturally arises is: what are they all doing? Well, they are incredibly busy…

First things first, bacteria are not all bad! The inherent bias against microbes stems from Pasteur’s work in the 1860s; he developed Germ Theory and identified microbes as the cause of some diseases. Many microbes do indeed cause disease (they are known as pathogens). However, many microbes are neutral, and some are actually crucial to human health! One important role that these ‘good’ bacteria play is crowding out the ‘bad’ bacteria by competing for nutrients, preventing the pathogens multiplying and causing infections.

Credit: Whitaker, Weston R. Et al. Cell, Volume 169, Issue 3, pp 538 – 546

Every individual’s microbiome is different, the types and number of bacteria can act as a unique identifier (a fingerprint, of sorts). The microbiome is roughly the weight of the human brain and is now described as an organ because it carries out some crucial jobs for the body. I thought I’d explore some of these jobs and look at how disturbing the microbiome may lead to disease.

Bacteria in the gut have an important role in digesting nutrients that we can’t break down ourselves (they also help in producing vitamins, like K12). An example of these nutrients are xyloglucans, found in lettuce and onions, that a specific species of Bacteroides break down for us. This metabolic outsourcing is commonplace as it reduces the energy humans need to exert during digestion and means we do not need to encode a protein to break down every single nutrient in our diet!

This microbiome role lead to the idea that gut bacteria could be responsible for obesity. Interestingly, the type and amount of bacterial species in the gut differ significantly between obese and lean people. For example, M. smithii is seen in higher numbers in lean individuals compared to obese individuals whereas Blautia is more prevalent in people with high visceral fat mass. This is all very correlative; it doesn’t show that the differences cause obesity (maybe the different diets of obese people change the species of bacteria able to survive). However, there is some evidence suggesting the bacteria can cause, or at least contribute to, obesity. Many studies utilise germ-free mice which are raised in sterile conditions (even their food is irradiated) and so have no microbiota. If you transfer an obese person’s microbiome (via faeces) to germ-free mice, the mice develop obesity and their metabolism changes. These types of results are spurring drug developers to look to microbe based therapies to treat obesity, such as faecal transplants. I don’t know about you, but I am excited by the idea of crapsules!

Credit: Alan W. Walker & Julian Parkhill Science 06 Sep 2013: Vol. 341, Issue 6150, pp. 1069-1070

If the idea of the microbiome having a role in obesity is a logical jump, the idea of the microbiome having a role in disorders of the brain and nervous system is a leap. Yet, it’s been shown that microbiome transplants from human Parkinson’s patients into a mice model of the disease makes the mice’s symptoms worse.  No one is completely sure of the mechanism behind this, it is likely to be due to the microbiome’s interactions with the immune system. The brain has its own immune cells – microglia- that are over-activated in Parkinson’s and cause inflammation that damages nerve cells. Or, it could be that the microbes are producing certain products from digestion – short chain fatty acids – that cause nerve cells to accumulate dangerous lumps of proteins inside them (the protein in Parkinson’s is called α-synuclein) and then these lumps activate the microglia. The symptoms of Parkinson’s are debilitating movement problems that deteriorate relatively quickly; movements become slow, muscles rigid and there is also significant cognitive decline. Consequently, the possibility that pro-biotic drinks or changes in the diet to alter the microbiome could be effective treatments is tantalising.

Credit: Sampson, Timothy R. Et al. Cell, Volume 167, Issue 6, pp 1469 – 1480

What I hope I’ve portrayed here is that the trillions of microbes on and inside our bodies have crucially important roles to keep us healthy. Disturbing this huge community of bacteria in our gut may lead to obesity and maybe even disorders of the brain. There are both friends and foes in our gut – we’d be lost without them.

 

 

Jack Gordon

Biomedical science undergraduate interested in genetics, neuroscience, cancer research and the pharmaceutical industry.