| Bacteroides thetaiotaomicron | |
|---|---|
 | |
Scientific classification | |
| Domain: | Bacteria |
| Kingdom: | Pseudomonadati |
| Phylum: | Bacteroidota |
| Class: | Bacteroidia |
| Order: | Bacteroidales |
| Family: | Bacteroidaceae |
| Genus: | Bacteroides |
| Species: | B. thetaiotaomicron |
| Binomial name | |
| Bacteroides thetaiotaomicron (Distaso 1912) Castellani and Chalmers 1919 | |
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 theBacteroides genus – a group that is known for its role in the complex microbial community of thegut microbiota. Itsproteome, consisting of 4,779 members, includes a system for obtaining and breaking down dietarypolysaccharides that would otherwise be difficult to digest for the human body.[1]
The bacterium encodes for enzymes such asglycoside hydrolases and polysaccharide lyases, allowing it to break down dietary fibers, such as cellulose and hemicellulose, into fermentable substrates. This metabolic activity generatesshort-chain fatty acids (SCFAs) like acetate and propionate, which are absorbed by the host and provide critical energy sources for colonic cells.[2]
B. thetaiotaomicron is anopportunistic pathogen and may becomevirulent inimmunocompromised individuals.B. thetaiotaomicron has been associated with other commensal bacteria and the induction of regulatoryT cells, which are essential for maintaining immune tolerance and preventing excessive inflammatory response in the gut mucosa.[3]Due to its adaptability and interaction with the host immune and metabolic systems,B. thetaiotaomicron serves as a model organism for studyingsymbiosis,microbial ecology, and gut-host interactions.
Bacteroides thetaiotaomicron was first described in 1912 under the nameBacillus thetaiotaomicron and moved to thegenusBacteroides in 1919.[4] Thespecific name derives from theGreek letterstheta,iota, andomicron; theList of Prokaryotic names with Standing in Nomenclature indicates this as "relating to the morphology of vacuolated forms."[4] The name is used as an example of an "arbitrary" species name in theInternational Code of Nomenclature of Prokaryotes.[5][6] TheBacteroidota bacterial phylum, distinguished by its unique motility, is present in a wide range of ecosystems, habitats, lifestyles, and physiological conditions.[7] The genusBacteroides 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.[8]
Bacteroides thetaiotaomicron is a common bacterium in the human gutmicrobiome 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 specializedenzymes 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.[1]
The evolution ofB. 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 theweaning period of an infant. During thesuckling 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.[9] 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 andB. thetaiotaomicron benefit, showing how interconnected the gut microbiome and human health have become.[10][11]
The evolution of cooperation within the gut microbiota, specifically involvingBacteroides thetaiotaomicron, highlights how gut microbes adapt to coexist and even cooperate with each other and their hosts. This cooperation allowsB. 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.[12]
Bacteroides thetaiotaomicron has been isolated from humans, cattle, pigs, goats and mice.[13][14] TheBacteroides thetaiotaomicron strain GA17 is specifically associated with humans.[15]
Thegenome ofB. thetaiotaomicron was sequenced in 2003. It is one circular chromosome of double stranded DNA. It is 6.26megabases in length, but has a relatively small number of distinctgenes. This is due to genes coding forproteins that are unusually large compared to otherprokaryotes.[16] This genomic feature is shared with another member of the genus,Bacteroides fragilis.[17] Extensive 16S rRNA count by theHuman Microbiome Project (HMP) found the genome contains genes associated with breaking downpolysaccharides includingglycoside hydrolases (GHs) and polysaccharide lyases (PLs), along withstarch binding proteins.[16][17][18]
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 byB. thetaiotaomicron or through Sus are converted into monosaccharides which can then be absorbed by human cells for metabolism.[19][16] 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.[16]
These genes along with ECF-type sigma factors allowB. thetaiotaomicron to correlate the availability of nutrients with expression of the particular genes.[16] The genome also contains many genes that encode proteins involved in sensing and responding to the extracellular environment, such assigma factors andtwo-component systems.[16][20][21] Thecolocalization 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.[16] TheB. thetaiotaomicron genome encodes a large number ofsmall non-coding RNAs, which also play a key role in regulatory processes, though few have been characterized to date.[22]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 betweenBacteroides species as well as other gut microbiota.[16]
Bacteroides thetaiotaomicron is capable of metabolizing a very diverse range of otherwise indigestiblepolysaccharides, likeamylose,amylopectin, andpullulan.[20] Its complement ofenzymes used forhydrolysis ofglycosidic bonds is among the largest known inprokaryotes, and is even thought to be capable of hydrolyzing nearly all glycosidic bonds in biological polysaccharides. As the major organism of the humangut flora to break down plant polysaccharides, it can use dietarycarbohydrates, as well as those sourced from thehost, depending on nutrient availability.[23] Complex plant polysaccharides, unlike simplemonosaccharides anddisaccharides that are digested and absorbed in the small intestines, are left to be used as a food source in the colon.[19] Complex polysaccharides are fermented in the colon to produceshort chain fatty acids (SCFAs) like acetate and propionate. These SCFAs serve as energy sources forcolonocytes and have anti-inflammatory properties[2]B. thetaiotaomicron also relies on glycolysis, theEmbden-Meyerhof-Parnas (EMP) pathway, andfermentation to metabolize sugars.[24]
B. thetaiotaomicron is able to dominate the many other gut bacteria in the human colon by using its superior ability to acquire sufficient nutrients.[19] This is possible due to the combined effects of an increased amount ofglycosyl hydrolases that degrade enzymes, membrane binding proteins, and sugar-specific transporters.[19] There are 172 glycosylhydrolases produced byB. thetaiotaomicron which is greater than any other sequenced bacterium, providing to enzymes that contribute products of hydrolysis to the host.[19] All Bacteriodes employ polysaccharide-utilization loci (PULs) whose gene clusters encode systems that target and degrade carbohydrates.[25] 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.[25]
B. thetaiotaomicron isaerotolerant and can survive, but not grow, when exposed tooxygen. Oxygen has limited access in eukaryotic host environments, like the human intestines. Generation ofreactive oxygen species (ROS) such as hydrogen peroxide may occur, threatening the flora by attacking iron cofactors enzymes widely used in metabolism.[26] To drive the oxygen concentration to lower levels,B. thetaiotaomicron expresses a number of proteins that scavenge ROS such ashydrogen peroxide when exposed to air.[26]
Members of the genusBacteroides accounts for about a quarter of the microbial population in an adult human's intestine. In a long-term study ofBacteroides species in clinical samples,B. thetaiotaomicron was the second most common species isolated, behindBacteroides fragilis.[26] It is crucial to humans, as it is able to digest plant materials that enzymes within the gut cannot.[16]
B. thetaiotaomicron is acommensal, a type ofsymbiosis, meaning it provides the host with key benefits like digestion.[16][17]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.[20] 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.[19] It also has the ability to regulate epithelialglycan 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 forB. thetaiotaomicron to maintain its preferred environmental conditions.[16]
Previous studies show thatB. thetaiotaomicron stimulatesangiogenesis, which is the formation of new blood vessels, during intestinal development following birth. These studies usedgerm-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.[16]
B. thetaiotaomicron dominates the intestinal microbiome and also aids in another postnatal development of the gut with the formation of themucosal barrier in the intestine, which plays a major role in maintaining host-microbiota homeostasis.[27][28] The mucosal barrier, located between the intestinal epithelium and microbiota, is semipermeable, allowing the uptake of essential nutrients while restricting the passage ofpathogenic molecules.[27][29] Nearly 90% of the bacteria within the gut microbiota, colonizing the gastrointestinal tract (GIT), belongs to the Bacteroidetes or Firmicutes phyla.[27]B. thetaiotaomicron's ability to grow on host-derived polysaccharides in mucus is a major contributor to its persistence in the GIT.[27]
TheBacteroides species has the ability to produce distinctlipopolysaccharides (LPS) that suggests it has the potential to modify innate immunity, asglycolipids are known to communicate with the immune system of mammals, particularly through sensing the surrounding bacteria. These LPS structures exhibit a laddered pattern, indicative of an O antigen; however,B. thetaiotaomicron specifically, produces small lipooligosaccharides (LOS) with the absence of an O antigen. The abundance of these LPS and LOS indicate they could function to allow communication between the host and commensal microbes.[8]
B. thetaiotaomicron is a prominent member of the human gut microbiota, and its role in the immune response is complex. The interaction betweenB. 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 bacteriaB. thetaiotaomicron are evident, along with the identification of the molecular mechanisms governing their interaction with innate immune cells.[30]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.[3][31]
The outer membrane vesicles (OMVs) not only aid in protectingB. thetaiotaomicron from degradation, but also play a major role in promoting regulatorydendritic cell responses. OMVs ofB. thetaiotaomicron ina healthy gut stimulate colonic dendritic cells (DC) to expressIL-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 withulcerative colitis (UC) andCrohn'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).[32][better source needed]
B. thetaiotaomicron is also anopportunistic pathogen and can infect tissues exposed to gut flora.[26] While contained in the gut,B. thetaiotaomicron generally maintains a beneficial relationship with its host. However, it can present harmful effects if it is introduced to other areas of the body that are not equipped to effectively interact with this type of bacteria. In the case of a rupture in thegastrointestinal tract,B. thetaiotaomicron as well as other gut bacteria can be released from the intestines.[17] This can lead to diseases likebacteremia, which is the presence of bacteria in the bloodstream.B. thetaiotaomicron can also cause bacterial infection in tissue which elicits an immune response and promotesabscess formation.
Due to its polysaccharide-metabolizing abilities,B. thetaiotaomicron contributes to the food source of other components in the gutmicrobiome. For example, the bacteria expresssialidase enzymes, but they cannot catabolizesialic acid. Consequently, their presence increases the amount of available sialic acid in the gut that can be utilized by other organisms for energy. This specific ability allows for the growth of pathogenic bacteria such asClostridioides difficile, which uses sialic acid as a carbon source.[33] Similarly,B. thetaiotaomicron has been shown to exacerbate pathogenicE. coli infection due to its ability to enrich the availability of nutrients for pathogens such asE. coli .[34]B. thetaiotaomicron's enzymatic properties enable it to further thrive in the competitive environment of the human intestine.
Due to its ability to break down complex polysaccharides, particularly those found in the dietary fibers that humans cannot digest properly,B. thetaiotaomicron has become a model microbe to understand the microbiota in the human gut.[35]B. thetaiotaomicron plays a notable role in gut health, specially regarding its anti-inflammatory properties, which are important in conditions likeinflammatory bowel disease (IBD) andCrohn's disease.[36] Research oncolitis, a form of IBD, has shown thatB. thetaiotaomicron enhances the mucosal barrier, modulates the immune response of the gut microbiota, and counteracts thedysbiosis typically observed in IBD patients, highlighting the role ofB. thetaiotaomicron in preventing chronic inflammation.[34] In a study of inflammatory bowel disease (IBD) in mice,B. thetaiotaomicron was found to alleviate colitis when combined withFaecalibacterium prausnitzii. When combined withFaecalibacterium prausnitzii, B. thetaiotaomicron proved to a qualified bacterium to be used for fecal microbiota transplantation, and overall future therapeutic reports.[37]
Its fully sequenced genome allowsB. thetaiotaomicron to undergo genetic manipulation. The genome is altered to understand the host-bacteria interaction, and interactions with other microbes.[38] It was found thatB. thetaiotaomicron could be engineered to maintain long-term storage of responses to environmental conditions. This could lead to the ability to monitor effects of surface polysaccharides, colonization, and overall gut health of the host.[39] Research has also indicated that when exposed tobile,B. thetaiotaomicron develops physiological adaptations, allowing it to increase its colonization capacity. These bile induced adaptations include enhanced stress tolerance mechanisms and increased production ofefflux pumps which ultimately provide cross-protection against harmful agents such asantibiotics. However, the bile concentration required to enable these adaptions can only be accessed in certain parts of the gut.[40]
Bacteroides thetaiotaomicron has been evaluated as an indicator of fecal pollution.[41] Fecal matter from different host species results in various health risks.[42] For example, enteric viruses from humans account for most gastrointestinal illnesses while infectious parasites tend to be transferred from livestock.[43] Identifying the origin of fecal matter is the first step in understanding the risk of contact, as well as how to eliminate the threat of contamination. It was found that the specificB. thetaiotaomicron marker, particularly the human-associatedBacteroides thetaiotaomicron strain GA17,[15] was an accurate indicator of fecal contamination.[44] The presence ofB. thetaiotaomicron is greater in humans than nonhumans, making this a good indicator of the presence of human feces.[45] The accuracy of the test combined with faster analysis times of identifyingB. thetaiotaomicron in samples makes these bacteria – or thebacteriophages that infect them[46] – a qualifying contender for future fecal pollution identification.[44]