The effect of early-life prebiotic feeding on adult rat hippocampal function, central and peripheral metabonomics and microbial metagenomics

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Scientists have shown that growing good bacteria in our guts can improve some brain functions, such as memory. We have found that when rats eat a compound called BGOS, good gut bacteria grow and there is an increase in the levels of two molecules, called the NMDA receptor and BDNF, in a brain area called the hippocampus. These molecules and the hippocampus are very important for memory function. We have also found that rat pups that eat BGOS shortly after they are born, contain higher levels of NMDA receptors and BDNF in their hippocampus when they are adults compared to animals that did not eat BGOS when they were young. We therefore, wonder whether the changes in NMDA receptors and BDNF we see in the older brain after BGOS at a younger age, actually change the function of the brain. We are also interested in whether BGOS feeding in rat pups changes the chemical processes, called metabolism, in the brain and body when they get older. Finally, we would like to see if rats being fed BGOS at a young age, contain different types of gut bacteria when they get older, compared to rats that were not given BGOS.Rat pups will be fed with BGOS when they are 3 days old, and then once every day until they 21 days old. While they are given BGOS, the pups will be allowed to stay with their mothers and breast-feed. Other rats will be given a sugar compound (placebo) which is like BGOS but does not grow gut bacteria. When all the rats are 22 days old, they will be put into different cages, given normal adult food and water, and allowed to grow. We will then do four different experiments: 1) When some rats are 22, 56, 112 or 196 days old, they will be humanely killed and their brains removed. The hippocampus of rats at each age that were fed BGOS or placebo, will be taken out for electrophysiology. This is a technique that measures the electrical activity in brain tissue generated when neurotransmitters travel between brain cells. Scientists have shown that changes in the levels of NMDA receptors and BDNF change electrical activity in the hippocampus and affects memory. We therefore, predict that BGOS feeding increases hippocampus electrical activity compared to the hippocampus from placebo fed animals. 2) Rats that had been fed BGOS or placebo at a young age, will be subjected to memory tests when they are 22, 56, 112 or 196 days old. In these tests, the animals will be put into mazes where they have to learn and remember how to get a food reward. The hippocampus is important for this test, and scientists have shown that changes in the levels of NMDA receptors and BDNF in the hippocampus can change the activity of this brain area and how well a rat can remember. We predict that rats that had been fed BGOS will do the memory tasks better than placebo fed animals at all ages. 3) We will look at the concentration of molecules that are made from metabolism, in the brain, liver, blood and urine of all rats at all ages. The approach we will use is called metabonomics, which is a fast way to look at thousands of molecules in one sample, and hundreds of samples at the same time, in order to detect changes that tells us about metabolism. 4) We will use a method called metagenomics to measure the different type of bacteria, and their amounts in the droppings of all rats at all ages. This approach is a bit like metabonomics, except that thousands of bacteria, instead of metabolic molecules, can be identified and counted in one sample, and hundreds of samples can be processed together. This experiment will show us if taking BGOS at an early age will make good gut bacteria continue grow as the rat gets older. Overall, the study will tell us if BGOS feeding from an early age improves memory, metabolism and the growth of good gut bacteria as the body and brain get older. If it does, then growing good bacteria with BGOS in children might make them more healthy in life and resistant to some diseases.