SYMBIOSIS-What They Don’t Teach You in School

By Michael Wade

Symbiosis is an intimate relationship between two organisms where both organisms benefit directly from each other. Most symbiosis occurs between plants or animals and microbes. We have symbiotic bacteria in our guts that break down food into smaller molecules that our intestinal cells can absorb and the bacteria in return get food and a protective environment. Establishing a symbiotic relationship among many different animals (vertebrates and invertebrates) with their microbial counterparts is an important relationship that is detrimental to the fitness of the host.

Figure 1: Complexity of gut microbiota contributions to host physiology

The role of symbiotic relationships goes beyond just a beneficial one-in some situations, the host actually requires infection of microbes in order for that infected tissue to develop properly! An example of this is seen in germ-free rats in a sterile environment. The beginning of the large intestine, or the cecum, is enlarged in germ-free rats, and has been attributed to reproductive and functional gastrointestinal disorders. Germ-free mice also have problems absorbing nutrients due to a reduction in the villous capillary networks in the GI tract, have a smaller surface area of gut, have abnormal bile acid metabolism and have a reduced rate in systemic cholesterol metabolism. In invertebrate species, such as the Hawaiian bobtail squid Euprymna scolopes, a restructuring of the light organ crypt is seen that is similar to that in the GI tract of mice once its symbiont, Vibrio fischeri, establishes an infection. In the crypt, the epithelial cells swell and increase microvillar density and increase mucus secretion. However, there are also changes to remote tissues that don’t interact directly with V. fischeri, such as surface epithelial fields and ducts, to undergo remodeling by inducing apoptosis in these cells. There is also a gradual loss of surface ciliated epithelium that occurs post infection.

 Figure 2. Regression of ciliated epithelialium post V. fischeri infection (top) and remodeling of light organ (bottom).

Like in Euprymna scolopes, gut microbes in mammals affect the development of systems outside the GI tract. The cardiovascular system in germ-free mice is impaired in several ways, including a decreased cardiac output, and a reduced myocardial weight. The nervous system is also abnormal and underdeveloped in these mice. There is also evidence that the gut microbiota play a role in brain development and behavior, and can lead to brain disorders including reduced anxiety and an abnormal stress response. In humans, the gut microbiota has been linked to autism, Alzheimer’s, and Huntington’s disease in that patients with autism have unusual levels of gut microbiota, and patients with Alzheimer’s or their gut microbiota have a greater propensity to metabolize bile acids.

Figure 3. Comparison of abdomen of germ-free (left) and normal (right)

There is a misconception, even within the scientific community, that the role of the immune system is to fight pathogens and remove them from the host. However, that statement has been shown in many cases to be an inaccurate description. In fact, the immune system (both the adaptive and innate immune system) REQUIRES bacteria in order to develop properly. Germ-free animals have shown to have a number of adaptive immune response problems, including poorly formed spleens and lymph nodes, abnormal numbers of immune cell types, decreased lymphoid follicles, and decreased secreted IgA and IgG.

 Figure 4: Overview of some interactions with gut microbiota and host immune system

The adaptive immune system of germ-free mice is underdeveloped. There is a lack of CD4+ T helper cells, and T17 cells, which is reversible, both locally and systemically, upon the addition of only one strain of gut bacteria (which later was shown to be a capsular antigen). This is amazing considering that many different species of bacteria reside in the gut of mice, but only the presence of one bacterial species triggers the development and balance (cell types, cell numbers, and proper cytokines) of the adaptive immune response through a specific dendritic cell. In invertebrate species that lack an adaptive immune system, like the Hawaiian bobtail squid Euprymna scolopes, the phagocytic response of the innate immune system changes only after Vibrio fischeri colonizes the light organ.

As we investigate the role of symbiosis, we find more and more interesting connections between the host and its microbiota. The establishment of the symbiotic microbes at a young age is of great importance in that some of the developmental changes that arise after infection are irreversible after a certain point.  There are many more interesting stories of symbiosis, but telling them all would be a lengthy task. A couple of those topics include links to obesity, inflammatory bowel disease, liver disease, allergies, type 1 diabetes and cell-cell signaling(host-resident micobiota, resident-pathogen, and host-pathogen signaling).

References:

Nyholm, S.V., and M.J. McFall-Ngai. 2004. The Winnowing-Establishing the Squid-Vibrio Symbiosis. Nature 2:632-642.

Sekirov, I., Russel, S.L.,Antunes, L.C.M., and Brett Finlay. 2010. Gut microbiota in health and disease. Physiological Reviews. 3:859-904.

Collins, A.J., Schleicher, T.R., Rader, B.A., and Spencer V. Nyholm. 2010. Understanding the role of hemocytes in a squidVibrio symbiosis using transcriptomics and proteomics. Frontiers in Immunoogy. 3:1-14.

Gross, R., Vavre, F., Heddi, A., Hurst, G. D. D., Zchori-Fein, E., and Kostas Bourtzis. 2009. Immunity and symbiosis. Molecular Microbiology. 73:751-759.

Images:

Figure 1: Gut microbiota in health and disease

Figure 2: The Winnowing-Establishing the Squid-Vibrio Symbiosis (top) Mcro 424 lecture PDF

Figure 3: http://www.narl.org.tw/en/topic/topic.php?topic_id=1

Figure 4: http://www.aat-taa.eu/index/en/research/host-bacteria-interaction.html