Bacteroides Influence on Host Behavior
Introduction
Bacteria often live in a special mutualism with large multicellular organisms: one such relationship of particular interest is that of the human digestive system and its "gut flora", or the microbial life that colonizes it. It is fairly intuitive that in such a relationship the host will dictate temperature, pH level, substrate availability, and a variety of other environmental factors that will determine what types of bacteria are able to colonize it, how these bacteria will behave, and how successful any given species will be in that environment. What is not always such an intuitive aspect of the host/bacteria relationship is the role that the bacteria may play in the behavior and physiology of the host.
The rise in obesity in the western world over the past several decades has prompted researchers to explore possible explanations for this drastic shift in human physiology. An important determinant of the physiology of an individual is that individual's particular genome; and while this may account for a natural tendency towards weight gain for certain genotypes, the human genome has certainly not undergone a radical transformation since the "obesity epidemic" hit the western world. If we look at what has changed in the past few decades, we see people consuming larger-portioned, higer-calorie diets. But how and why does this shift in diet translate to a shift in body composition? Scientists are now looking at the role of the human body as a host to a plethora of bacteria, in particular, the inhabitants of the human gut—referred to collectively as the microbia. The gut flora engage in a key mutualistic relationship with the host, aiding in digestion. The microbia is composed of approximately 1013 organisms that fall into somewhere between 500 and 1,000 distinct species of bacteria (REF2). Of these bacteria the classes Bacteriodes and Firmicutes make up a substantial portion: over 90% of all gut flora fall into one of the two classes (REF3).
Bacteriodes is a gram-negative, rod-shaped bacteria. It resides in the human/mammalian cecum where it ferments polysaccharides from plant fibers using anaerobic respiration. The substrates catalyzed by bacteroides cannot be broken down by host enzymes, but once fermented by bacteriodes can be used and/or stored as energy by the host. It is estimated that up to 15% of the caloric value humans obtain from food is made available to us by bacteriodes (REF), making it a key player to consider when examining the pathway from diet to physiology. Its vital role in energy processes has prompted researcher to explore the role that bacteroides and other bacteria may be playing in the rise in obesity. More specifically put: perhaps the shift to the modern western diet is manipulated/exploited by our gut flora—resulting in a change in body composition and weight.
Host/Bacteria Relationship
Humans do not have the ability to catabolize a significant amount of the substrates we consume, we simply lack the enzymes and other tools necessary to execute certain metabolic pathways. The reason we are still able to derive energy from these substrates is that the extensive community of microbes living in the human digestive tract metabolizes these molecules for us. An ancient mutualism between host organisms and the bacteria that colonize them has relieved humans of the need to develop such pathways. There are more microbial organisms present in the human gut than the sum total of all of our somatic and gametic cells (REF); they essentially compose a functional organ of the human body. The species that compose this "organ" represent every branch of life—eukaryotes, bacteria, and even some archaea—but by far the most populous inhabitants are the bacteria. This community of microorganisms reaches the highest population density of any form of life in any ecosystem anywhere on the planet (REF 4). Interestingly enough, this high population density is not reflected by a high species diversity: the digestive system is home to relatively few species, which are dominated by the genera Bacteroides and Firmicutes—when combined, these two compose over 90% of all the phylogenetic types present (REF 3).
In ecosystems with high species diversity equilibrium is maintained because a broad range of species with a broad range of functions will be able to fill a diverse set of niches. As the boom-bust pattern of bacterial growth cycles due to availability of substrate, predation, and a variety of other factors, new species are able to fill the voids left by species that have "busted". The ecosystem of the human gut, however, does not have a range of species with a range of functions. Rather, equilibrium is maintained because each individual species can fill a broad spectrum of functions (REF5). A major factor that contributes to the stability of the digestive tract ecosystem is that the microbes of the intestine are able to induce changes in the host to bring their environment into equilibrium. The most extensively studied species in this area is the keystone member of the gut flora: Bacteroides thetaiotaomicron.
A closer look at Bacteroides thetaiotaomicron
In the human microbiota B. thetaiotaomicron is the most abundant species, it is a 'keystone' member of the gut ecosystem. B. thetaiotaomicron is the first abundant member of the human gut flora to have its entire genome sequenced. Analysis of the genome revealed a massive proteome, with some 4,779 predicted proteins of which 24% have no homology to other known sequences, and 18% have homology to proteins with no known functions (REF5). The large portion of proteins with no known homologs indicates a deep-branch in its lineage. The remaining 58% of proteins of known function offer insight into how this organism maintains its dominance in the ecosystem of the human gut. Dr. Xu posits that the success of B. thetaiotaomicron can largely be attributed to three factors: "(i) sensing its luminal environment, (ii) acquiring dietary polysaccharides, and (iii) manipulating host gene expression in ways that establish and maintain a mutually advantageous environment"(REF5). B. thetaiotaomicron has the ability to derive energy from a broad range of sources, preferring food particles followed by shed elements of the mucus layer, and lastly exfoliated epithelial cells (REF2). If a preferred food is not available to it , B. thetaiotaomicron will use host polysaccharides. It does this by manipulating the host genome; for example, it can promote host epithelial cell production of fucosylated glycans on which to feed.
Manipulation of Host Gene Expression and Physiology
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Possible Therapeutic Options
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Conclusion
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References
1. Backhed, F., Ding, H., Wang, T., Hooper, L., Koh, G.Y., Nagy, A., Semenkovich, C.F., Gordon, J.I. "The gut microbiota as an environmental factor that regulates fat storage". Science. 2004. Volume 101(44). p. 15718-15723.
2. Backhed, F., Ley, R.E., Sonnenburg, J.L., Peterson, D.A., Gordon, J.I. "Host-Bacterial Mutualism in the Human Intestine". Science. 2005. Volume 307. p. 1915-1920.
3. McCann, K.S. “The diversity-stability debate”. Nature. 2000. Vol. 405. p. 228]
4. Turnbaugh, P.J., Ley, R.E., Mahowald, M.A., Magrini, V., Mardis, E.R., Gordon, J.I. "An obesity-associated gut microbiome with increased capacity for energy harvest". Nature. 2006. Volume 444. p. 1027-131.]
5. Xu, J., Bjursell, M.K., Himrod, J., Deng, S., Carmichael, L.K., Chiang, H.C., Hooper, L.V., Gordon, J.I. "A Genomic View of the Human-Bacteroides thetaiotaomicron Symbiosis". Science 2003. Vol.299. p.2074-2076.
6. Ferretti, J.J., Gilmore, M.S. "The Thin Line Between Gut Commensal and Pathogen". Science. 2003. Volume 299. p. 1999-2002.
Edited by student of Joan Slonczewski for BIOL 238 Microbiology, 2009, Kenyon College.
