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Monday, February 6, 2012

Your gut is inside out


Recently, I had dinner with my granddaughter Bella (11+) in our favourite restaurant and in the course of the conversation I asked her if she thought her gut was inside her or outside her. She gave me that “Grand Dad, stop being foolish” look. I then challenged with the fact that when we were children, her Uncle Fintan swallowed a threepenny bit (detour to explain) and that when our mother recovered it from his stool, it was in mint condition after a quick wash. “If it was inside him, how come it came out again” I asked only to be given that same look. Out gut is not inside us. It is simply a hollow tube from mouth to anus and in order to get “inside” us you have to cross the gut wall. Grand Dad’s are not always wrong.

Among the organs of the body, the gut is the least loved. It is always associated with the privacy of toilets and from time to time the terrors of food poisoning with trouble at both ends. In fact the gut is not only a very complex organ but it is a very intelligent organ. Not long after conception, a neural crest is formed which will eventually form the human brain. However, it splits and most of the crest goes to the brain while the rest forms the amazing nervous system of the gut. The two are then connected by the vagus nerve. There is more nervous tissue in the gut than in the spinal cord, which carries all the nervous material from the brain to all the organs of the body.  If you think about it, you experience your “gut brain” regularly. Think of the phrases we use: “He hadn’t the guts for it” or “I had butterflies in my tummy” or “I had a gut feeling”. All these phrases point to our awareness of the gut in times of stress. The gut consumes a large amount of the blood flow of the body and when there is trouble ahead, this blood flow falls to enable greater flow to the brain. When the trouble requires us to flee, we may do so having either suddenly emptied our bowels either end, or we flee with no further toilet stops.  There is another reason why our gut needs a brain, which is localised. If we encounter a deadly poison from some bacteria in our gut, it pays to get rid of it very rapidly. Any delay in connecting the toxin to the systemic immune system might just be long enough for permanent damage to be done. Thus the gut induces either vomiting or diarrhea to expel the toxin.

A second major feature of our gut is the colonisation of the gut, particularly the large bowel, with bacteria. Once upon a time, these bacteria were seen as no more than a bioprocessing unit, breaking down the fibrous components of our diet which our digestive enzymes cannot handle. Now we know that these bacteria play a major role in many aspects of our metabolism and our immune system. The human body is warm and moist and thus it attracts bacteria on all outer surfaces most notably the skin and the gut. The latter is not only warm and moist but it is also laden with nutrients. It pays, therefore, for man to have evolved a mutual relationship with favourable forms of bacteria in return for housing them in our gut. In effect, we have a peace treaty with our gut microbes: They keep away pathogens and we house and feed them. There is now very considerable interest in the role our gut microflora play in our everyday health. Their range of genetic material is 100 times greater than ours and some of these genes directly influence our genes in directing metabolism. Their role in obesity is attracting very considerable interest

It is possible to raise mice that have no colonic bacteria, referred to as germ-free. Experiments with conventional and germ-free mice fed an identical high fat diet, show that whereas the conventional animals will get fat, the germ free animals resist this trend and remain lean. These researchers went one step further and looked at a protein found in blood called Fasting-Induced Adipocyte Factor (FIAF). The cells of our gut wall can produce this protein but our normal gut bacteria suppress its manufacture: one of many examples of their genome telling our genome what to do! FIAF blocks the uptake of fats from blood into our adipose tissue stores. By slowing down FIAF release from the gut, the bacteria are now allowing fat to move from blood into adipose tissue. In germ-free animals, there is no such suppression and FIAF blocks the uptake of fat into adipose tissue. To test the link between germ free animals and obesity, the team then genetically engineered these mice to block FIAF synthesis. The germ-free mice now got fat. Thus, in addition to making a good bioreactor for the extraction of maximum calories from food, the gut microbes keep a check on FIAF allowing fat to move from blood into adipose tissue. That our gut bacteria talk to our adipose tissue via FIAF might wake us up to pay more attention to their welfare. 

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