What do you think you are? (post 2 of 2)

To continue fromwhere we left off in the previous post (you may want to go back and read that if you haven’t) let’s look at another evolutionary arguments for the importance of our microbiome. Bacteria have been colonising humans since we first existed. Human eating habits have changed a lot within a very short period. Throughout much of our evolutionary time we have eaten a diet ripe in bacteria – meat caught and slaughtered outside, vegetables grown naturally in fields and so on. However, within recent times our food production (and consumption) has changed. Processed foods have become increasingly common, and these are largely sterile. Additionally, antibiotics are heavily used in the animal farming industry; reducing the amount of bacteria we receive from our food. Some claim that this may be disrupting our microbiome, as we are not getting the same level and diversity of bacteria. Furthermore, this disruption caused by out eating habits may be playing a role in the development of obesity in the Western world. Obviously the diet itself plays a major role in obesity, but the microbiome may also contribute. Consider the fact that if we have a gut full of bacterial cells all needing energy, they are going to take what they need from the food we ingest, before we absorb it for ourselves. If we have less microbes, in the gut, and less coming in with our food, then less energy will be taken out of the system, potentially allowing more to enter into our bodies; this excess of energy may well be play a significant role in obesity.

The use of antibiotics by farmers also argues for a role of the microbiome in obesity. The reason antibiotics are used by farmers is from the observation that this practice caused a gain of weight in the animals. For a long time this was not understood, but now with the evidence emerging from humans and other animal studies it appears that this affect could be down to the depletion of the microbiome caused by the antibiotics. A further example comes from studies in mice which have shown that transplanting the microbiome from an obese mouse into a thin mouse leads to weight gain. The reverse has also been seen. If this holds true in humans then targeting the microbiome may be a feasible way to tackle the obesity epidemic of the Western world.

Changing tack slightly, as you may be aware, antibiotics have been overused for a long time, leading to major worries over antibiotic resistance and reversion to a pre-antibiotic era. This is a huge worry, however the overuse of antibiotics may have additional consequences that we are only just starting to realise. It has been found that people in the Western world are now largely devoid of the bacterium Helicobacter pylori, which is common in the guts of people in areas of the world less rife in the use of antibiotics. Removal of H. pylori isn't a bad thing per se; this bacterium is known to cause peptic ulcers and stomach cancer. However, the importance of H. pylori is a nice shade of grey and we have only noticed the beneficial effects now it’s gone.

H. pylori plays an important role in controlling stomach acid production and people devoid of it are at a much higher risk of developing acid reflux. Acid reflux can lead to a condition known as Barrett's oesophagus and eventually certain forms of oesophageal cancer if left untreated. Coincidently with the loss of H. pylori from the gut microbiome in the West, rates of oesophageal cancer have soared. Furthermore, H. pylori is able to control inflammatory responses. This control may be important for regulating allergies, which are caused by an inappropriate inflammatory response against something harmless (such as pollen). Similarly to the rates of oesophageal cancer, it is well documented that there are an increasing number of people with allergies in the Western world. Finally, H. pylori may also be important in obesity, as it is known to regulate the hormone ghrelin, which regulates our appetite. All of this has led to some suggestions that we should inoculate babies with H. pylori. Obviously this raises ethical issues because of the potential for peptic ulcers and stomach cancer, but these are largely only seen later in life. The current idea is that we should inoculate at a young age and then give antibiotics to kill the bacteria later in life, getting the best of both worlds.

A mentioned, H. pylori may be playing a role in the inflammatory response and development of allergies. However, the link between resident bacteria and the immune system doesn’t end there. It appears that our whole microbiome is essential for the development of a proper immune system that doesn't attack the wrong things. Without the bacteria in our guts it is thought that the immune system may become hypersensitive and attack everything, leading to allergies.

Histological section of intestine lining

Sticking with the immune system, many chronic diseases have inflammation as an underlying cause. Inflammation is an essential part of our immune response, but is only beneficial if it is transient; sustained inflammation leads to damage around the body. It has been found that Bifidobacteria and Lactobacilus species in the gut are essential for maintenance of the epithelial lining in this organ (the cells that make up the walls of our gut). A proper epithelial lining plays an essential role in the passage of nutrients out of our digestive system into our blood. The lining needs to be ‘selectively permeable’ so that only certain, useful, things get through. If the lining becomes ‘leaky’, then unwanted molecules can get through such as bacteria and their toxins or whole protein molecules (instead of just the amino acids we normally absorb from the gut), all of which could trigger an inappropriate immune response. Since Bifidobacteria and Lactobacilus are needed for maintenance of the epithelial lining, any disruption to these bacteria will have an impact on the integrity of the barrier. Indeed, it has been shown that mice fed on a "junk food" diet have a disruption of these bacteria and develop a ‘leaky epithelia’. This caused a low level systemic inflammatory response, which eventually causes metabolic diseases. It is therefore highly possible that many disease with inflammation as an underlying cause could originate from issues with out internal bacterial species.

The final thing I'd like to discuss is that the notion of thinking with your gut may hold more truth than you know. It has been found that microbes in the gut are important for the generation of neurotransmitter molecules such as serotonin and thus may be playing an important role in regulating mood. Furthermore, there is evidence suggesting a link between the gut microbiome and the hypothalamic-pituitary axis (HPA), a region of the brain that shows disruption during clinical depressive episodes. Mice bred to have no microbiome show an enhanced stress response that can be curtailed by the introduction of a microbiome - this response, to a large extent, is generated from the HPA. Additionally, it been shown in mice that if the microbiome of adventurous mice is transplanted into the guts of timid mice they lose their inhibitions and become more adventurous, further supporting the notion that our gut bacteria may be influencing our brains.

It may be scary to think that we are only 10% human with the remainder being made up by microbes, the majority of which are bacteria. What may be even scarier to consider is that these bacteria may have an influence on our most evolutionarily important organ, the brain. Bacteria could be controlling our response to stress; they could also potentially have even broader and larger effects on our behaviours and mood. Additionally to affecting our brains, there is increasing evidence that the gut microbiome plays essential roles in our immune system and may even play a huge role in obesity. Obesity is one of the biggest issues in the Western world and any methods to tackle it are rightly gaining much attention. Since we can alter our gut microbiome through the foods we eat and the drugs we take it stands to reason that with increased research in the area we may be able to shape our microbiomes to tackle disease. Since the microbiome seems to affect so many different aspects of our physiology, altering it will be fraught with potential pit-falls. But to look at it in a more positive light, we may be able to tackle a plethora of diseases in a very simple and affordable manner. Bacteria tend to get a bad reputation, but without them we probably wouldn’t be here.