You Are What You Eat
There is an estimated 10-100 trillion bacteria and other microorganisms living in the human digestive system, forming a mutualistic relationship in which all species benefit. Recently, much research has been done on the role of these microorganisms in the development of disease, the brain, and behavior.
- The BLOOD BRAIN BARRIER is a layer of cells lining the blood vessels within the brain, acting as a filter that controls the molecules that pass between the blood and the brain. - An organism's GUT MICROBIOTA is the collection of all the microorganisms (e.g. bacteria, phages, fungi) that live inside the digestive system of that individual. - A TIGHT JUNCTION is a type of intercellular protein connection between animal cells that prevents leakage of materials through the space between the cells. - The transmembrane protein OCCLUDIN is one of the component proteins of a tight junction. - GERM-FREE MICE lack all microorganisms in their digestive systems, a state achieved by delivering them through cesarean section and raising them in sterile incubators. - PATHOGEN-FREE MICE are raised under sterile conditions to limit their exposure to disease-causing microorganisms.
This study illustrates how one study can open additional questions for future research. The primary finding of this study indicates that the maternal gut microbiota play a role in the development and regulation of the BBB in mice from embryonic development throughout adulthood.
- What is the precise signaling pathway that gut microbiota use to regulate the function of the BBB? - What are the specific effects of short chain fatty acids produced by the gut microbiota on the development and maintenance of the central nervous system? - What is the precise mechanism of how tight junction protein gene expression is controlled in GF and PF mice? - What are the consequences of increased BBB permeability in GF mice throughout life?
One of the most important science practices is analyzing and interpreting graphical representations of data. Such representations and analyses can help bring out the meaning in the data. The researchers involved in this study employed many techniques to test the hypothesis that the maternal gut microbiota could influence the development and maintenance of the BBB. Analyze the figures in the online paper to evaluate the following statements.
According to the gel electrophoresis Western blot in Figure 1, the tight junction protein occludin was expressed less in the brains of embryonic GF mice. SUPPORTED Due to the non-overlapping standard error of the mean bars in Figure 1G, the occludin protein likely plays a role in the lack of an effective BBB in embryonic GF mice. SUPPORTED According to Figure 4, there was significantly less expression of both occludin and claudin-5 proteins in all three regions of the brains of adult GF mice as compared to adult PF mice. SUPPORTED According to Figure 4, the number of intact tight junctions in the striatum of GF adult mice was lower than that in the PF adult mice. SUPPORTED Figure 5 shows that as a result of fecal transplantation, there was statistically significant higher expression of the occludin and claudin-5 proteins in all regions of the brains of colonized adult mice as compared to the GF adult mice. NOT SUPPORTED Figure 6 shows that the presence of short chain fatty acids restored the expression of the ZO-1 protein, one of the key components of tight junctions. NOT SUPPORTED
The scientists demonstrated that mice who are germ-free for their entire lives fail to develop normal tight junctions (Figures 1-4). As a result, these mice have abnormally permeable BBBs. These findings led the researchers to their next question and experiment.
Colonization of the gut microbiota of germ-free adult mice will restore a functional BBB. HYPOTHESIS Fecal transfer, or not, of normal gut microbiota from pathogen-free adult mice to germ-free adult mice. INDEPENDENT VARIABLE The BBB permeability and the expression levels of the main tight junction proteins. DEPENDENT VARIABLE Germ-free adult mice that did receive the fecal transfer (the "conventionalized" mice). EXPERIMENTAL GROUP Germ-free adult mice that did not receive the fecal transfer. NEGATIVE CONTROL GROUP Within the first two weeks after fecal transfer, the BBB of "conventionalized" germ-free mice was restored as indicated by the decrease in its permeability; the expression of tight junction proteins increased. RESULT
An intact blood brain barrier (BBB) is vital to the development and function of the brain. It controls the exchange of materials between the circulatory system and the brain.
The BBB of germ-free mice were more permeable than those of pathogen-free mice, the structural deficiencies persisted into adulthood, and introducing normal microbiota could improve the BBB function.