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Molecular Dialogues with the Microbes Inside Us ~A talk by Dr. Karen Guillemin
There is a new understanding that based off of the 10 trillion cells that compose is ~25,000 genes and in getting close to knowing all of our genes, it has been discovered that the gastrointestinal tract has 10^14 cells (~1,000 species) which is roughly 2,500,000 genes. This number easily dwarfs that of the human genome.
Since Antoni Van Leeuwenhoek (A Dutch merchant) developed his town lenses for a hand-held microscope, there have been various ideas as to how we view the body and assess the host-microbe relationship.
The Germ Theory of Disease is one such view. Louis Pasteur and Robert Koch both said that diseases were able to spread because they contained spreadable agents within the microbes. This ideology gave microbes a bad name and blamed them for diseases that we couldn't see and therefore had difficulty treating. Around WWII there was the implementation of penicillin that paved the way for other antibiotics to fight against harmful pathogens
In her talk, Dr. Guillemin poses 3 main questions:
1) How did they get there?
2) How stable are gut microbial communities?
3) Can changes in the microbe community cause diseases?
In answer to the first question: How do they get there, we looked at birthing methods and the microbes that are associated with each. When the mother gave birth vaginally, the baby showed more microbes from that region of the body. If it was a cesarean section, the baby exhibited more of the mother's skin microbes. There is also the matter that when mothers nurse their babies, the breast milk contains sugars that the human body cannot break down. This promotes the symbiotic relationship between humans and our gut microbes.
How stable are gut microbial communities? This is a flexing question since there have been a vast number of changes in human ecology so we have altered the microbes that live inside us. We have made a shift to being more sterile, our food is more processed, and the change in birthing routes (now 1/3 of the country's births are cesarean sections). This shift has greatly cut down on the microbial biodiversity that has helped us historically. It is yet to be determined what the consequences to this are but there are some theories, which leads us to question 3:
Can changes in the microbe community cause diseases? The Hygiene Hypothesis (David Strachan 1989) says that if we are cleaner and avoid microbes, we are putting ourselves at a greater risk for developing auto-immune diseases. The Disappearing Microbiota Hypothesis (Blaser and Falkow 2009) says that the microbes in our bodies are more than just a random occurrence and we are losing the microorganisms that have been important historically. This second hypothesis questions whether or not the altered microbiota in diseases are a cause or consequence of this.
Dr. Guillemin described the work that was being done with Zebrafish to determine if altered microbiota in diseases were the cause or consequence of the loss of microbes. Zebrafish are ideal model animals since they are similar to humans in the inter workings and they are easy to examine since they are transparent and their genes are easy to manipulate. This image shows that the introduction of microbes into zebrafish greatly reduces, if not completely stopping the gut motility found in the fish. An experiment was done to see if the bacteria that was introduced caused inflammation of the gut in a sterile zebrafish. First, they started with a mutant fish strain who exhibited not gut motility, was defective in gut clearing and thus, had inflamed guts. To test whether or not this was a direct result of the bacteria introduced, the bacteria was extracted (gut motility visible, reduced inflammation) and then reintroduced into the system (no gut motility and inflammation had returned). This experiment showed that the inflammation was due to the microbiota and that the gut microbial community in the mutant fish caused transmissible intestinal inflammation - microbes drive the disease.
So what does that mean?
Many advances are being made, but we are still unsure of a great number of the inter workings of the microbial community within us. Some things that Dr. Guillemin suggests we do to promote our body's microbial community are to nurture our gut microbes by using antibiotics judiciously and avoiding over processed foods, and to nurture environmental microbes through supporting the responsible use of antibiotics in agriculture and animal husbandry as well as supporting efforts to reduce human impacts on the environment.