Bacteroides thetaiotaomicron is a Gram-negative, obligate anaerobic bacterium and a prominent member of the human gut microbiota, particularly within the large intestine. B. thetaiotaomicron belongs to the Bacteroides genus – a group that is known for its role in the complex microbial community of the gut microbiota. Its proteome, consisting of 4,779 members, includes a system for obtaining and breaking down dietary polysaccharides that would otherwise be difficult to digest for the human body.
The bacterium encodes for enzymes such as glycoside hydrolases and polysaccharide lyases, allowing it to break down dietary fibers, such as cellulose and hemicellulose, into fermentable substrates. This metabolic activity generates short-chain fatty acids (SCFAs) like acetate and propionate, which are absorbed by the host and provide critical energy sources for colonic cells.
B. thetaiotaomicron is an opportunistic pathogen and may become virulent in immunocompromised individuals. 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 in the gut mucosa. Due to its adaptability and interaction with the host immune and metabolic systems, B. thetaiotaomicron serves as a model organism for studying symbiosis, microbial ecology, and gut-host interactions.
History and taxonomy Bacteroides thetaiotaomicron was first described in 1912 under the name Bacillus thetaiotaomicron and moved to the genus Bacteroides in 1919. 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 name is used as an example of an "arbitrary" species name in the International Code of Nomenclature of Prokaryotes. The Bacteroidota bacterial phylum, distinguished by its unique motility, is present in a wide range of ecosystems, habitats, lifestyles, and physiological conditions. The genus Bacteroides represents the most prominent bacteria in the gut of humans, particularly those in western civilizations. Though it is found in abundance in humans, the exact distribution varies between individuals and can be affected by the host's genome, diet, and other factors.
Evolution Bacteroides thetaiotaomicron is a common bacterium in the human gut microbiome that has evolved alongside humans to support digestion and general health. Over time, this bacterium developed the ability to break down complex carbohydrates into simple sugars, which helps the host species get more energy from the food it eats. B. thetaiotaomicron has a range of specialized enzymes that allow it to process various plant fibers and other dietary components found in the human gut. Because of these adaptations, it has become an essential part of the gut ecosystem, benefiting both itself and the host by playing a big role in maintaining a balanced microbiome.
The evolution of B. thetaiotaomicron seems to have been shaped by the changing diet and immune systems of its human hosts, which influenced the bacterium's genetic and functional traits. For example, it has genes that help it detect and respond to different nutrients, which makes it more resilient in the face of dietary changes. Bacteroides thetaiotaomicron prefers nutrients during different periods of the host's life, particularly before and after the weaning period of an infant. During the suckling period, the oligosaccharides found in the mother's milk and other carbohydrates from the host are preferred. After the weaning period, it prefers plant-derived polysaccharides, such as those found in diets. It also plays a role in regulating the host's immune system, reducing inflammation and contributing to a stable gut environment. This relationship reflects a complex co-evolution where both the human host and B. thetaiotaomicron benefit, showing how interconnected the gut microbiome and human health have become.
The evolution of cooperation within the gut microbiota, specifically involving Bacteroides thetaiotaomicron, highlights how gut microbes adapt to coexist and even cooperate with each other and their hosts. This cooperation allows B. thetaiotaomicron to access nutrients and survive in the complex, competitive gut environment. Over time, evolutionary pressures have shaped this bacterium's metabolic pathways and communication mechanisms, enabling it to thrive in symbiosis with its host, enhancing both microbial survival and host health through mutualistic interactions.
Host range Bacteroides thetaiotaomicron has been isolated from humans, cattle, pigs, goats and mice. The Bacteroides thetaiotaomicron strain GA17 is specifically associated with humans.
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. This is 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. Extensive 16S rRNA count by the Human Microbiome Project (HMP) found the genome contains genes associated with breaking down polysaccharides including glycoside hydrolases (GHs) and polysaccharide lyases (PLs), along with starch binding proteins.
B. thetaiotaomicron has a starch utilization system (Sus), which allows the bacteria to bind complex polysaccharides to the cell surface and the outer membrane enzymes break them down into simple sugars. The polysaccharides that are digested by B. thetaiotaomicron or through Sus are converted into monosaccharides which can then be absorbed by human cells for metabolism. The utilization of Sus allows this bacterium to regulate complex polysaccharide expression that allows an advantage over other bacteria that are unable to regulate their environment.
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 that encode 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 create 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 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. Complex polysaccharides are fermented in the colon to produce short chain fatty acids (SCFAs) like acetate and propionate. These SCFAs serve as energy sources for colonocytes and have anti-inflammatory properties B. thetaiotaomicron also relies on glycolysis, the Embden-Meyerhof-Parnas (EMP) pathway, and fermentation to metabolize sugars.
B. thetaiotaomicron is able to dominate the many other gut bacteria in the human colon by 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, providing 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 a 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. It also has the ability to regulate epithelial glycan synthesis, a process that involves its ability to sense surrounding nutrient availability, such as in the lumen of the gut. It is able to detect nutrients and deploy host enzymes that build and modify glycans when there are few present in their environment. This regulation mechanism allows for B. thetaiotaomicron to maintain its preferred environmental conditions.
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.