Bacteroides thetaiotaomicron

Bacteroides thetaiotaomicron is a gram-negative, rod shaped obligate anaerobic bacterium that is a prominent member of the normal gut microbiome in the distal intestines. Its proteome, consisting of 4,779 members, includes a system for obtaining and breaking down dietary polysaccharides that would otherwise be difficult to digest. B. thetaiotaomicron is also an opportunistic pathogen, meaning it may become virulent in immunocompromised individuals. It is often used in research as a model organism for functional studies of the human microbiota.

History and taxonomy
Bacteroides thetaiotaomicron was first described in 1912 under the name Bacillus thetaiotaomicron and moved to the genus Bacteroides in 1919. The B. thetaiotaomicron type strain VPI-5482 was originally isolated from a healthy adult's human feces. The specific name derives from the Greek letters theta, iota, and omicron; the List of Prokaryotic names with Standing in Nomenclature indicates this as "relating to the morphology of vacuolated forms". The Bacteroidota bacterial phylum, distinguished by its unique motility, is present in a wide range of ecosystems, habitats, lifestyles, and physiological conditions. The name is used as an example of an "arbitrary" species name in the International Code of Nomenclature of Prokaryotes.

Genome
The genome of B. thetaiotaomicron was sequenced in 2003. It is one circular chromosome of double stranded DNA. It is 6.26 megabases in length, but has a relatively small number of distinct genes, due to genes coding for proteins that are unusually large compared to other prokaryotes. This genomic feature is shared with another member of the genus, Bacteroides fragilis. The genome contains genes associated with breaking down polysaccharides, including glycoside hydrolases and starch binding proteins. These genes along with ECF-type sigma factors allow B. thetaiotaomicron to correlate the availability of nutrients with expression of the particular genes. The genome also contains many genes encoding proteins involved in sensing and responding to the extracellular environment, such as sigma factors and two-component systems. The colocalization of the gene encoding digestive enzymes with extracytoplasmic function sigma factors and signal transduction systems creates a mechanism that regulates gene expression based on the availability of nutrients in the environment. The B. thetaiotaomicron genome encodes a large number of small non-coding RNAs which also play a key role in regulatory processes, though few have been characterized to date. B. thetaiotaomicron has several different types of mobile genetic elements, including a 33 kilobase plasmid, 63 transposases, and four homologs of the conjugative transposon CTnDOT. CTnDOT encodes the resistance to the antibiotics erythromycin and tetracycline, and is horizontally transferred between Bacteroides species as well as other gut microbiota.

Metabolism
Bacteroides thetaiotaomicron is capable of metabolizing a very diverse range of otherwise indigestible polysaccharides, like amylose, amylopectin, and pullulan. Its complement of enzymes used for hydrolysis of glycosidic bonds is among the largest known in prokaryotes, and is even thought to be capable of hydrolyzing nearly all glycosidic bonds in biological polysaccharides. As the major organism of the human gut flora to break down plant polysaccharides it can use both dietary carbohydrates, as well as those sourced from the host, depending on nutrient availability. Complex plant polysaccharides, unlike simple monosaccharides and disaccharides that are digested and absorbed in the small intestines, are left to be used as a food source in the colon. B. thetaiotaomicron is able to dominate the many other gut bacteria living within the human colonic environment using its superior ability to acquire sufficient nutrients. This is possible due to the combined effects of an increased amount of glycosyl hydrolases, that degrade enzymes, membrane binding proteins, and sugar-specific transporters. There are 172 glycosylhydrolases produced by B. thetaiotaomicron which is greater than any other sequenced bacterium, contributing to enzymes that contribute products of hydrolysis to the host. All Bacteriodes employ polysaccharide-utilization loci (PULs) whose gene clusters encode systems that target and degrade carbohydrates. A part of these systems are carbohydrate-active enzymes (CAZymes) that can very efficiently degrade complex carbohydrates found in the diet. There have been three different PULs identified that use RG-II, a dietary carbohydrate with the most structural complexity, as a substrate The RG-II degradome contains 23 enzymes that target sequential glycosidic linkage in the RG-II, leading to its disassembly.

B. thetaiotaomicron is aerotolerant and can survive, but not grow, when exposed to oxygen. Oxygen has limited access in eukaryotic host environments, like the human intestines. Generation of reactive oxygen species (ROS) such as hydrogen peroxide may occur, threatening the flora by attacking iron cofactors enzymes widely used in metabolism. To drive the oxygen concentration to lower levels, B. thetaiotaomicron expresses a number of proteins that scavenge ROS such as hydrogen peroxide when exposed to air.

Role in the human microbiome
Members of the genus Bacteroides accounts for about a quarter of the microbial population in an adult human's intestine. In a long-term study of Bacteroides species in clinical samples, B. thetaiotaomicron was the second most common species isolated, behind Bacteroides fragilis. It is crucial to humans as it is able to digest plant materials that enzymes within the gut cannot.

B. thetaiotaomicron is considered commensal, a type of symbiosis, meaning it provides the host with key benefits like digestion. B. thetaiotaomicron has far more glycosyl hydrolases, in which 61% are located in the outer membrane or extracellular matrix, suggesting that the digestive capabilities serve the bacteria's host more than anything. The glycosyl hydrolases express 23 specific enzymatic functions that supply the host or even other microbes in the gut flora with the breakdown products of hydrolysis. The polysaccharides that are digested by B. thetaiotaomicron are converted into monosaccharides which can then be absorbed by human cells for metabolism.

Previous studies show that B. thetaiotaomicron stimulates angiogenesis, which is the formation of new blood vessels, during intestinal development following birth. These studies used germ-free mice in order to control the microbiota and inoculated the mice with a specific bacteria, B. thetaiotaomicron. Angiogenesis further benefits the host by increasing the human's ability to absorb the nutrients that the microbe assists in produce.

B. thetaiotaomicron dominates the intestinal microbiome and also aids in another postnatal development of the gut with the formation of the mucosal barrier in the intestine, which plays a major role in maintaining host-microbiota homeostasis. The mucosal barrier, located between the intestinal epithelium and microbiota, is semipermeable, allowing the uptake of essential nutrients while restricting the passage of pathogenic molecules. Nearly 90% of the bacteria within the gut microbiota, colonizing the gastrointestinal tract (GIT), belongs to the Bacteroidetes or Firmicutes phyla. B. thetaiotaomicron's ability to grow on host-derived polysaccharides in mucus is a major contributor to its persistence in the GIT.

Role in immune response
B. thetaiotaomicron is a prominent member of the human gut microbiota, and its role in the immune response is complex. The interaction between B. thetaiotaomicron and the immune system contributes to the maintenance of gut homeostasis and the development of an immune system. The anti-inflammatory and immunomodulatory characteristics of extracellular vesicles generated by the prevalent human gut bacteria B. thetaiotaomicron are evident, along with the identification of the molecular mechanisms governing their interaction with innate immune cells. B.thetaiotaomicron has been associated with other commensal bacteria and the induction of regulatory T cells which are essential for maintaining immune tolerance and preventing excessive inflammatory response.

The outer membrane vesicles (OMVs) not only aid in protecting B. thetaiotaomicron from degradation, but also play a major role in promoting regulatory dendritic cell responses. OMVs of B. thetaiotaomicron in a healthy gut stimulate colonic dendritic cells (DC) to express IL-10. T-cells are stimulated by IL-10 and is expressed via the innate immune system through macrophages and DC. B. thetaiotaomicron OMVs in individuals with ulcerative colitis (UC) and Crohn's disease (CD) are unable to stimulate IL-10 expression, resulting in a loss of regulatory DC. In these diseases, B. thetaiotaomicron OMVs also cause a significantly lower amount of DC to be expressed. These results were also observed in patients with the inactive diseases, signifying that the defects in immune response are intrinsic in inflammatory bowel disease (IBD).

Pathology
B. thetaiotaomicron is also an opportunistic pathogen and can infect tissues exposed to gut flora. While contained in the gut, B. thetaiotaomicron generally maintains a beneficial relationship with its host. However, the bacteria can cause serious pathology when it is present in an inappropriate environment. Bacteria can escape the gut as a result of a rupture of the gastrointestinal tract. This can lead to diseases like bacteremia, which is the presence of bacteria in the bloodstream. It can also lead to abscess formation, which occurs when an area of tissue is infected and the body's immune system sends white blood cells to try to fight and contain it.

Its polysaccharide-metabolizing abilities make it a food source for other components of the gut microbiome. For example, while B. thetaiotaomicron expresses sialidase enzymes, it cannot catabolize sialic acid; as a result its presence increases the free sialic acid available for other organisms in the gut to use as an energy source. These interactions can contribute to the growth of pathogenic bacteria such as Clostridium difficile, which uses sialic acid as a carbon source. Similar interactions can cause B. thetaiotaomicron to exacerbate pathogenic E. coli infection. These strategies allow B. thetaiotaomicron to further thrive in the competitive environment of the human intestine.