Gut flora
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2008-06-19T22:28:14Z
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[[Image:EscherichiaColi NIAID.jpg|thumb|right|''[[Escherichia coli]]'', one of the many species of bacteria present in the human gut.]]
The '''gut flora''' are the [[microorganisms]] that normally live in the [[digestive tract]] and can perform a number of useful functions for their hosts. Though widely known as the "intestinal microflora", this is technically a misnomer since the word root "flora" pertains to plants and biota refers to microbial life such as bacteria other than plants. Thus the more appropriate term "intestinal microbiota" is coming into use, though its use has not eclipsed the entrenched use and recognition of "flora" with regard to intestinal bacteria, and for the time being, both terms are being used in different textbooks.
The average human body, consisting of about 10<sup>13</sup> (10,000,000,000,000 or about ten trillion) [[cell (biology)|cells]], has about ten times that number of microorganisms in the gut.<ref name="Björkstén">Björkstén B, Sepp E, Julge K, Voor T, and Mikelsaar M. 2001. Allergy development and the intestinal microflora during the first year of life. ''Journal of Allergy and Clinical Immunology'', Volume 108, Issue 4, Pages 516-520. PMID 11590374.</ref><ref name="Guarner and Malagelada 2003b">Guarner F and Malagelada JR. 2003. Gut flora in health and disease. ''The Lancet'', Volume 361, Issue 9356, 8 February 2003, Pages 512-519. PMID 12583961.</ref><ref name="Sears">Sears CL. 2005. A dynamic partnership: Celebrating our gut flora. ''Anaerobe'', Volume 11, Issue 5, Pages 247-251. PMID 16701579.</ref><ref name="Steinhoff">Steinhoff U. 2005. Who controls the crowd? New findings and old questions about the intestinal microflora. ''Immunology Letters'', Volume 99, Issue 1, 15 June , Pages 12-16. PMID 15894105. </ref>
[[Bacteria]] make up most of the flora in the [[colon (anatomy)|colon]]<ref name="University of Glasgow"> University of Glasgow. 2005. [http://web.archive.org/web/20040526195616/http://www.gla.ac.uk/departments/humannutrition/students/resources/meden/Infection.pdf The normal gut flora.] Available through web archive. Accessed [[May 22]], [[2008]]</ref> and 60% of the mass of [[feces]].<ref name="Guarner and Malagelada 2003b"/> Somewhere between 300<ref name="Guarner and Malagelada 2003b"/> and 1000 different [[species]] live in the gut,<ref name="Sears"/> with most estimates at about 500.<ref name="gibson">Gibson RG. 2004. Fibre and effects on probiotics (the prebiotic concept). ''Clinical Nutrition Supplements'', Volume 1, Issue 2, Pages 25-31. </ref><ref name="Steinhoff"/> However, it is probable that 99% of the bacteria come from about 30 or 40 species.<ref name="Beaugerie L and Petit JC">Beaugerie L and Petit JC. 2004. Microbial-gut interactions in health and disease. Antibiotic-associated diarrhoea. ''Best Practice & Research Clinical Gastroenterology'', Volume 18, Issue 2, Pages 337-352. PMID 15123074.</ref> [[Fungi]] and [[protozoa]] also make up a part of the gut flora, but little is known about their activities.
Research suggests that the relationship between gut [[flora (microbiology)|flora]]<ref>Gut flora are also known as ''gut microbiota''.</ref> and humans is not merely [[commensalism|commensal]] (a non-harmful coexistence), but rather is a [[mutualistic]], [[symbiotic]] relationship.<ref name="Sears"/> Though people can survive with no gut flora,<ref name="Steinhoff"/> the microorganisms perform a host of useful functions, such as [[Fermentation (biochemistry)|fermenting]] unused energy substrates, training the [[immune system]], preventing growth of harmful species,<ref name="Guarner and Malagelada 2003b"/> regulating the development of the gut, producing vitamins for the host (such as [[biotin]] and [[vitamin K]]), and producing hormones to direct the host to store fats. However, in certain conditions, some species are thought to be capable of causing [[disease]] by causing [[infection]] or increasing [[cancer]] risk for the host.<ref name="Guarner and Malagelada 2003b"/><ref name="University of Glasgow"/>
==Localization==
The colon has the greatest numbers of bacteria and the most different species, and the activity of these bacteria make the colon the most [[metabolism|metabolically]] active [[organ (biology)|organ]] in the body.<ref name="gibson"/> Most of the bacteria in the small intestine are [[Gram staining|Gram-positive]], while those in the colon are mostly Gram-negative.<ref name="Riordan">Riordan SM, McIver CJ, Wakefield D, Duncombe VM, Thomas MC, and Bolin TD. 2001. Small intestinal mucosal immunity and morphometry in luminal overgrowth of indigenous gut flora. ''The American Journal of Gastroenterology'', Volume 96, Issue 2, Pages 494-500. PMID 11232696. Accessed [[September 15]], [[2007]]</ref> The first part of the colon is mostly responsible for fermenting [[carbohydrate]]s,<ref name="Beaugerie L and Petit JC"/><ref name="gibson"/><ref name="Guarner and Malagelada 2003b"/> while the latter part mostly breaks down [[protein]]s and [[amino acid]]s.<ref name="gibson"/><ref name="Guarner and Malagelada 2003b"/> Bacterial growth is rapid in the [[cecum]] and [[ascending colon]], which has a low [[pH]], and slow in the descending colon, which has an almost neutral pH.<ref name="Guarner and Malagelada 2003b"/> The body maintains the proper balance and locations of species by altering pH, the activity of the immune system, and [[peristalsis]].<ref name="University of Glasgow"/>
Over 99% of the bacteria in the gut are [[anaerobe]]s,<ref name="Beaugerie L and Petit JC"/><ref name="Guarner and Malagelada 2003b"/><ref name="University of Glasgow"/><ref name="Sears"/><ref name="Vedantam">Vedantam G and Hecht DW. 2003. Antibiotics and anaerobes of gut origin. ''Current Opinion in Microbiology'', Volume 6, Issue 5, Pages 457-461. PMID 14572537. Accessed [[September 15]], [[2007]]</ref> but in the [[cecum]] [[aerobic bacteria]] reach high densities.<ref name="Guarner and Malagelada 2003b"/>
==Types==
[[Image:Candida albicans.jpg|left|thumb|''[[Candida albicans]]'', a dimorphic fungus which grows as a yeast in the gut.]]
Not all the species in the gut have been identified<ref name="Guarner and Malagelada 2003b"/><ref name="Sears"/> because some cannot be cultured,<ref name="Beaugerie L and Petit JC"/><ref name="Sears"/><ref name ="Shanahan">Shanahan F. 2002. The host–microbe interface within the gut. ''Best Practice & Research Clinical Gastroenterology'', Volume 16, Issue 6, Pages 915-931. PMID 12473298. Accessed [[September 15]], [[2007]]</ref> so DNA isolation and identification is difficult.<ref name="Nordgård">Nordgård L, Traavik T, and Nielsen KM. 2005. Nucleic acid isolation from ecological samples—vertebrate gut flora. ''Methods in Enzymology'', Volume 395, Pages 38-48. PMID 15865959. Accessed [[September 7]], [[2007]]</ref> Populations of species vary widely among different individuals but stay fairly constant within an individual over time.<ref name="Guarner and Malagelada 2003b"/>. An effort to better describe the [[microflora]] of the gut and other body locations has been initiated; see [[Human microbiome project]].
Most bacteria come from the genera ''[[Bacteroides]]'', ''[[Clostridium]]'', ''[[Fusobacterium]]'',<ref name="Beaugerie L and Petit JC"/><ref name="Guarner and Malagelada 2003b"/><ref name="Vedantam"/> ''Eubacterium'', ''[[Ruminococcus]]'', ''[[Peptococcus]]'', ''[[Peptostreptococcus]]'', and ''[[Bifidobacterium]]''.<ref name="Guarner and Malagelada 2003b"/><ref name="Beaugerie L and Petit JC"/> Other genera such as ''[[Escherichia]]'' and ''[[Lactobacillus]]'' are present to a lesser extent.<ref name="Guarner and Malagelada 2003b"/> Species from the genus ''Bacteroides'' alone constitute about 30% of all bacteria in the gut, suggesting that that genus is especially important in the functioning of the host.<ref name="Sears"/>
The currently known genera of [[fungi]] of the gut flora include ''[[Candida (genus)|Candida]]'', ''[[Saccharomyces]]'', ''[[Aspergillus]]'', and ''[[Penicillium]]''.
==Acquisition of gut flora in human infants==
[[Image:Breastfeeding02.jpg|thumb|right|170px|[[Breastfeeding]] is one mode by which infants acquire gut flora.]]
The [[gastrointestinal tract]] of a normal [[fetus]] is sterile. During birth and rapidly thereafter, bacteria from the mother and the surrounding environment colonize the infant's gut. Immediately after vaginal delivery, babies have bacterial strains in the upper gastrointestinal tract derived from the mothers’ [[feces]].<ref name="Bettelheim">Bettelheim KA, Breadon A, Faiers MC, O'Farrell SM, Shooter RA. 1974. The origin of O serotypes of Escherichia coli in babies after normal delivery.
''Journal of Hygiene'', Volume 72, Issue 1, Pages 67-70. PMID 4593741. Accessed [[September 3]], [[2007]]</ref> Infants born by [[caesarean section]] may also be exposed to their mothers’ microflora, but the main exposure is from the surroundings.<ref name="Schwiertz">Schwiertz A, Gruhl B, Lobnitz M, Michel P, Radke M, Blaut M. 2003. Development of the intestinal bacterial composition in hospitalized preterm infants in comparison with breast-fed, full-term infants. ''Pediatric Research'', Volume 54, Issue 3, Pages 393-399. PMID 12788986. Accessed [[September 3]], [[2007]]</ref> After birth, environmental, oral and [[cutaneous]] bacteria are readily transferred from the mother to the infant through [[suckling]], kissing, and caressing.
All infants are initially colonized by large numbers of ''[[E. coli]]'' and [[streptococci]]. Within a few days, bacterial numbers reach 10<sup>8</sup> to 10<sup>10</sup> per gram of [[feces]].<ref name="Schwiertz"/><ref name="Mackie">Mackie RI, Sghir A, Gaskins HR. 1999.[http://www.ajcn.org/cgi/content/full/69/5/1035S Developmental microbial ecology of the neonatal gastrointestinal tract.] ''American Journal of Clinical Nutrition'', Volume 69, Issue 5, Pages 1035S-1045S. PMID 10232646. Accessed [[September 7]], [[2007]]</ref> During the first week of life, these bacteria create a [[reducing environment]] favorable for the subsequent bacterial [[succession]] of strict [[anaerobic organism|anaerobic species]] mainly belonging to the genera ''[[Bifidobacterium]]'', ''[[Bacteroides]]'', ''[[Clostridium]]'', and ''[[Ruminococcus]]''.<ref name="Favier">Favier CF, Vaughan EE, De Vos WM, Akkermans AD. 2002. [http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=11772630 Molecular monitoring of succession of bacterial communities in human neonates.] ''Applied and Environmental Microbiology'', Volume 68, Issue 1, Pages 219-226. PMID 11772630.</ref> [[weaning|Breast-fed]] babies become dominated by [[bifidobacteria]], possibly due to the contents of [[Bifidus factor|bifidobacterial growth factors]] in breast milk.<ref name="Coppa">Coppa GV, Bruni S, Morelli L, Soldi S, Gabrielli O. 2004. The first prebiotics in humans: human milk oligosaccharides. ''Journal of Clinical Gastroenterology'', Volume 38, Supplement 6, Pages S80-S83. PMID 15220665. Accessed [[September 3]], [[2007]]</ref> In contrast, the microflora of [[infant formula|formula-fed]] infants is more diverse with high numbers of ''[[Enterobacteriaceae]]'', [[enterococci]], [[bifidobacteria]], ''[[Bacteroides]]'', and [[clostridium|clostridia]].<ref name="Harmsen">Harmsen HJ, Wildeboer-Veloo AC, Raangs GC, Wagendorp AA, Klijn N, Bindels JG, Welling GW. 2000. Analysis of intestinal flora development in breast-fed and formula-fed infants by using molecular identification and detection methods. ''Journal of Pediatric Gastroenterology and Nutrition'', Volume 30, Issue 1, Pages 61-67. PMID 10630441. Accessed [[September 7]], [[2007]]</ref><ref name="Fanaro">Fanaro S, Chierici R, Guerrini P, Vigi V. 2003. Intestinal microflora in early infancy: composition and development. ''Acta Paediatrica'', Volume 91, Issue 441, Pages 48-55. PMID 14599042. Accessed [[September 3]], [[2007]]</ref> After the introduction of solid food and [[weaning]], the microflora of breast-fed infants becomes similar to that of formula-fed infants. By the second year of life the fecal microflora resembles that of adults.
==Functions==
Bacteria in the gut fulfills a host of useful functions for humans, including digestion of unutilized energy substrates;<ref name="Wynne">Wynne AG, McCartney AL, Brostoff J, Hudspith BN, Glenn GR and Gibson G. 2004. An ''in vitro'' assessment of the effects of broad-spectrum antibiotics on the human gut microflora and concomitant isolation of a Lactobacillus plantarum with anti-Candida activities. ''Anaerobe'', Volume 10, Issue 3, Pages 165-169. PMID 16701514. Accessed [[September 3]], [[2007]]</ref> stimulating cell growth; repressing the growth of harmful microorganisms; training the immune system to respond only to [[pathogen]]s; and defending against some diseases.<ref name="Guarner and Malagelada 2003b"/><ref name="Sears"/><ref name="Keeley">Keeley J. 2004. [http://www.eurekalert.org/pub_releases/2004-07/hhmi-gbt072104.php Good bacteria trigger proteins to protect the gut.] Howard Hughes Medical Institute. EurekAlert. Accessed [[January 9]], [[2007]]</ref>
===Carbohydrate fermentation and absorption===
Without gut flora, the human body would be unable to utilize some of the undigested [[carbohydrate]]s it consumes, because some types of gut flora have [[enzyme]]s that human cells lack for breaking down certain [[polysaccharide]]s.<ref name="Sears"/> Rodents raised in a sterile environment and lacking in gut flora need to eat 30% more [[calorie (food)|calories]] just to remain the same weight as their normal counterparts.<ref name="Sears"/> Carbohydrates that humans cannot [[digestion|digest]] without bacterial help include certain [[starch (food)|starches]]; [[fiber (food)|fiber]]; [[oligosaccharides]] and [[sugar]]s that the body failed to digest and absorb<ref name="gibson"/><ref name="Guarner and Malagelada 2003b"/><ref name="Beaugerie L and Petit JC"/> like [[lactose]] and sugar [[alcohol]]s, [[mucus]] produced by the gut, and proteins.<ref name="gibson"/>
Bacteria turn carbohydrates they ferment into [[short chain fatty acid]]s, or SCFAs.<ref name="gibson"/><ref name="University of Glasgow"/><ref name="Beaugerie L and Petit JC"/> These materials can be used by host cells, providing a major source of useful energy and nutrients for humans.<ref name="gibson"/> They increase the gut's absorption of water, reduce counts of damaging bacteria, increase growth of human gut cells,<ref name="University of Glasgow"/> and are also used for the growth of indigenous bacteria.<ref name="Guarner and Malagelada 2003b"/> The SCFAs are produced by a form of fermentation called [[saccharolytic fermentation]]<ref name="gibson"/> and include [[acetic acid]], [[propionic acid]], and [[butyric acid]].<ref name="gibson"/><ref name="University of Glasgow"/><ref name="Beaugerie L and Petit JC"/> Gases and [[organic acid]]s like [[lactic acid]] are also produced by saccahrolytic fermentation.<ref name="Beaugerie L and Petit JC"/> Acetic acid is used by [[muscle]], propionic acid helps the [[liver]] produce [[Adenosine triphosphate|ATP]], and butyric acid provides energy to gut cells and may prevent [[cancer]].<ref name="gibson"/>
Another, less favorable type of fermentation, [[proteolytic fermentation]], breaks down proteins like enzymes, dead host and bacterial cells, and [[collagen]] and [[elastin]] found in food, and can produce toxins and [[carcinogen]]s in addition to SCFAs. Thus a diet lower in protein lowers exposure to toxins.<ref name="Guarner and Malagelada 2003b"/><ref name="University of Glasgow"/>
Evidence also suggests that bacteria enhance the absorption and storage of [[lipids]].<ref name="Sears"/> Bacteria also produce and help the body absorb needed vitamins like vitamin K. In addition, the SCFAs they produce help the body absorb nutrients such as [[calcium]], [[magnesium]], and [[iron]].<ref name="Guarner and Malagelada 2003b"/>
===Trophic effects===
Another benefit of SCFAs is that they increase growth of intestinal [[epithelial cells]] and control their proliferation and differentiation.<ref name="Guarner and Malagelada 2003b"/> They may also cause [[lymphoid tissue]] near the gut to grow. Bacterial cells also alter intestinal growth by changing the expression of [[cell surface protein]]s such as [[sodium/glucose transporter]]s.<ref name="Sears"/> In addition, changes they make to cells may prevent injury to the gut [[mucosa]] from occurring.<ref name="Keeley"/>
===Repression of pathogenic microbial growth===
[[Image:Clostridium difficile 01.png|thumb|right|240px|''C. difficile'' colonies on a blood [[agar plate]]. The overgrowth of ''C. difficile'' in the gut can be harmful to the host.]]
Another important role of helpful gut flora is that they prevent species that would harm the host from colonizing the gut, an activity termed the "barrier effect". [[Yeast]]s and harmful bacterial species such as ''[[Clostridium difficile]]'' (the overgrowth of which can cause [[pseudomembranous colitis]]) are unable to grow too much due to competition from helpful gut flora species, thus animals without gut flora are [[infection|infected]] very easily. The barrier effect protects humans from both invading species and species normally present in the gut at low numbers, whose growth is usually inhibited by the gut flora.<ref name="Guarner and Malagelada 2003b"/>
Helpful bacteria prevent the growth of pathogenic species by competing for nutrition and [[bacterial attachment|attachment]] sites to the [[epithelium]] of the colon. Symbiotic bacteria are more at home in this ecological niche and are thus more successful in the competition. The indigenous bacteria send chemical signals to the host about the amount of nutrients they need, and the host provides only that much, so harmful bacteria are starved out. Indigenous gut flora also produce [[bacteriocins]], substances which kill harmful microbes and the levels of which can be regulated by enzymes produced by the host.<ref name="Guarner and Malagelada 2003b"/>
The process of fermentation, since it produces [[fatty acid]]s, also serves to lower the pH in the colon, preventing the proliferation of harmful species of bacteria and facilitating that of helpful species. The pH may also enhance the excretion of carcinogens.<ref name="gibson"/>
===Immunity===
Gut flora have a continuous and dynamic effect on the host's gut and systemic immune systems. The bacteria are key in promoting the early development of the gut's mucosal immune system both in terms of its physical components and function and continue to play a role later in life in its operation. The bacteria stimulate the lymphoid tissue associated with the gut mucosa to produce antibodies to pathogens. The immune system recognizes and fights harmful bacteria, but leaves the helpful species alone, a tolerance developed in infancy.<ref name="Guarner and Malagelada 2003b"/><ref name ="Shanahan"/><ref name="Steinhoff"/><ref name="University of Glasgow"/>
As soon as an infant is born, bacteria begin colonizing its digestive tract. The first bacteria to settle in are able to affect the [[immune response]], making it more favorable to their own survival and less so to competing species; thus the first bacteria to colonize the gut are important in determining the person's lifelong gut flora makeup. However, there is a shift at the time of [[weaning]] from predominantly [[facultative aerobic]] species such as ''[[Streptococci]]'' and ''[[Escherichia coli]]'' to mostly [[obligate anaerobic]] species.<ref name="Guarner and Malagelada 2003b"/><ref name="Sears"/>
Recent findings have shown that gut bacteria play a role in the expression of [[Toll-like receptors]] (TLRs) in the intestines, molecules that help the host repair damage due to injury. TLRs cause parts of the immune system to repair injury caused for example by [[radiation]].<ref name="Sears"/><ref name="Keeley"/>
Bacteria can influence the phenomenon known as [[oral tolerance]], in which the immune system is less sensitive to an [[antigen]] (including those produced by gut bacteria) once it has been ingested. This tolerance, mediated in part by the gastrointestinal immune system and in part by the liver, can reduce an overreactive immune response like those found in [[allergy|allergies]] and [[auto-immune disease]].<ref name="Jewell">Jewell AP. 2005. Is the liver an important site for the development of immune tolerance to tumours? ''Medical Hypotheses'', Volume 64, Issue 4, Pages 751-754. PMID 15694692. Accessed [[September 7]], [[2007]]</ref>
Some species of gut flora, such as some of those in the ''Bacteroides'' genus, are able to change their surface receptors to mimic those of host cells in order to evade immune response. Bacteria with neutral and harmful effects on the host can also use these types of strategies. The host immune system has also adapted to this activity, preventing overgrowth of harmful species.<ref name="Guarner and Malagelada 2003b"/><ref name="Steinhoff"/>
===Preventing allergy===
Bacteria are also implicated in preventing [[allergy|allergies]],<ref name="Björkstén"/> an overreaction of the immune system to non-harmful [[antigen]]s. Studies on the gut flora of infants and young children have shown that those who have or later develop allergies have different compositions of gut flora from those without allergies, with higher chances of having the harmful species ''[[clostridium difficile|C difficile]]''
and ''S aureus'' and lower prevalence of ''Bacteroides'' and ''Bifidobacteria''.<ref name="Björkstén"/> One explanation is that since helpful gut flora stimulate the immune system and "train" it to respond properly to antigens, a lack of these bacteria in early life leads to an inadequately trained immune system which overreacts to antigens.<ref name="Björkstén"/> On the other hand, the differences in flora could be a result, not a cause, of the allergies.<ref name="Björkstén"/>
===Preventing inflammatory bowel disease===
Another indicator that bacteria help train the immune system is the [[epidemiology]] of [[Inflammatory Bowel Disease]], or IBD, such as [[Crohn's Disease]] (CD). Some authors suggest that SCFAs prevent IBD. In addition, some forms of bacteria can prevent [[inflammation]].<ref name="Guarner and Malagelada, 2003a">Guarner F and Malagelada JR. 2003. Role of bacteria in experimental colitis. ''Best Practice & Research Clinical Gastroenterology'', Volume 17, Issue 5, October 2003, Pages 793-804. PMID 14507589. Accessed [[September 15]], [[2007]]</ref> The incidence and prevalence of IBD is high in [[industrialized countries]] with a high [[standard of living]] and low in [[less economically developed country|less economically developed countries]], having increased in developed countries throughout the twentieth century. The disease is also linked to good hygiene in youth; lack of breastfeeding; and consumption of large amounts of sucrose and animal fat.<ref name="Guarner and Malagelada, 2003a"/> Its incidence is inversely linked with poor sanitation during the first years of life and consumption of fruits, vegetables, and unprocessed foods.<ref name="Guarner and Malagelada, 2003a"/> Also, the use of antibiotics, which kill native gut flora and harmful infectious pathogens alike, especially during childhood, is associated with inflammatory bowel disease.<ref name="Wynne"/> On the other hand, using [[probiotic]]s, bacteria consumed as part of the diet that impart health benefits (aside from just [[nutrition]]), helps treat IBD.
==Alterations in balance==
===Effects of antibiotic use===
Altering the numbers of gut bacteria, for example by taking [[broad-spectrum antibiotic]]s, may affect the host's health and ability to digest food.<ref name="Carman">Carman RJ, Simon MA, Fernández H, Miller MA, and Bartholomew MJ. 2004. Ciprofloxacin at low levels disrupts colonization resistance of human fecal microflora growing in chemostats. ''Regulatory Toxicology and Pharmacology'', Volume 40, Issue 3, December, Pages 319-326. PMID 15546686. Accessed [[September 7]], [[2007]]</ref> People may take the drugs to cure bacterial illnesses or may unintentionally consume significant amounts of [[antibiotic]]s by eating the meat of animals to which they were fed.<ref name="Carman"/> Antibiotics can cause [[antibiotic-associated diarrhea]] (AAD) by irritating the [[bowel]] directly, changing the levels of gut flora, or allowing [[pathogen]]ic bacteria to grow.<ref name="Beaugerie L and Petit JC"/> Another harmful effect of antibiotics is the increase in numbers of [[antibiotic-resistant bacteria]] found after their use, which, when they invade the host, cause illnesses that are difficult to treat with antibiotics.<ref name="Carman"/>
Changing the numbers and species of gut flora can reduce the body's ability to ferment carbohydrates and metabolize [[bile]] acids and may cause diarrhea. Carbohydrates that are not broken down may absorb too much water and cause runny stools, or lack of SCFAs produced by gut flora could cause the diarrhea.<ref name="Beaugerie L and Petit JC"/>
A reduction in levels of native bacterial species also disrupts their ability to inhibit the growth of harmful species such as ''C. difficile'' and ''[[Salmonella kedougou]]'', and these species can get out of hand, though their overgrowth may be incidental and not be the true cause of diarrhea.<ref name="Beaugerie L and Petit JC"/><ref name="Carman"/><ref name="Guarner and Malagelada 2003b"/>
Gut flora composition also changes in severe illnesses, due not only to antibiotic use but also to such factors as [[ischemia]] of the gut, failure to eat, and [[immune compromise]]. Negative effects from this have led to interest in [[selective digestive tract decontamination]] (SDD), a treatment to kill only pathogenic bacteria and allow the reestablishment of healthy ones.<ref name="Knight">Knight DJW and Girling KJ. 2003. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12781578 Gut flora in health and disease.] ''The Lancet'', Volume 361, Issue 9371, Page 1831. Accessed [[January 7]], [[2007]]</ref>
===Probiotics & Prebiotics ===
Since the lack of gut flora can have such harmful health effects, the use of [[probiotics]] has anti-[[inflammation|inflammatory]] effects in the gut and may be useful for improving health. [[Prebiotic (nutrition)|Prebiotics]] are dietary components that can help foster the growth of microorganisms in the gut, which may lead to better health.<ref name="Guarner and Malagelada, 2003a"/>
==Role in disease==
Bacteria in the digestive tract have pathogenic properties in addition to their health-inducing ones: they can produce [[toxin]]s and [[carcinogen]]s<ref name="University of Glasgow"/> and have been implicated in such conditions as [[multisystem organ failure]], [[sepsis]], [[colon cancer]], and IBD.<ref name="Guarner and Malagelada 2003b"/> A major factor in health is the balance of bacterial numbers; if the numbers grow too high or low, it will result in harm to the host. The host has [[enzyme]]s to regulate this balance.<ref name="University of Glasgow"/>
===Cancer===
Some [[genus|genera]] of bacteria, such as ''Bacteroides'' and ''Clostridium'', have been associated with an increase in [[tumor]] growth rate, while other genera like ''Lactobacillus'' and ''Bifidobacteria'' are known to prevent tumor formation.<ref name="Guarner and Malagelada 2003b"/>
===Translocation===
Helpful bacteria can be very harmful to the host if they get outside of the intestinal tract.<ref name="Sears"/><ref name="University of Glasgow"/><ref name="Vedantam"/> [[Translocation]], which occurs when bacteria leave the gut through its [[mucosa]]l lining, the border between the [[lumen]] of the gut and the inside of the body,<ref name="Steinhoff"/><ref name="Suenaert">Suenaert P, Bulteel V, Lemmens L, Noman M, Geypens B, Assche GV, Geboes K, Ceuppens JL and Rutgeert P. 2002. Anti-tumor necrosis factor treatment restores the gut barrier in Crohn’s disease. ''The American Journal of Gastroenterology'', Volume 97, Issue 8, Pages 2000-2004. PMID 12190167. Accessed [[September 7]], [[2007]]</ref> can occur in a number of different diseases.<ref name="Vedantam"/><ref name="Guarner and Malagelada, 2003a"/> It can be caused by too much growth of bacteria in the small intestine, reduced immunity of the human, or increased gut lining permeability.<ref name="Guarner and Malagelada, 2003a"/> The gut can become more permeable in diseases like [[cirrhosis]], which is damaging due in part to the activity of gut flora.<ref name="Garcia-Tsao">Garcia-Tsao G and Wiest R. 2004. Gut microflora in the pathogenesis of the complications of cirrhosis. ''Best Practice & Research Clinical Gastroenterology'', Volume 18, Issue 2, Pages 353-372. PMID 15123075. Accessed [[September 7]], [[2007]]</ref>
If the gut is perforated, bacteria can invade the body, causing a potentially fatal infection. Aerobic bacteria can make infection by anaerobes worse by using up all available oxygen and creating an environment favorable to anaerobes.<ref name="Vedantam"/>
===Inflammatory bowel disease===
Some suspect that IBD is due to a reduction in immune tolerance and subsequent overreaction of the host's immune system to harmful or non-harmful bacteria. IBD may be caused by all of the gut flora together or some specific types.<ref name="Wynne"/><ref name="Hugot">Hugot JP. 2004. Inflammatory bowel disease: a complex group of genetic disorders. ''Best Practice & Research Clinical Gastroenterology'', Volume 18, Issue 3, Pages 451-462. PMID 15157820. Accessed [[September 7]], [[2007]] </ref>
It has been noted that though [[Ulcerative Colitis]] and [[Crohn's disease]] (two types of IBD) probably have [[Genetics|genetic]] components, they are not inherited in a [[Mendelian inheritance|Mendelian]] fashion and are thus probably due to a complex set of factors rather than solely to a [[gene]].<ref name="Hugot"/> Though neither bacterial colonization nor [[genetics]] is sufficient to cause the disease, bacteria probably play a role in these disorders.<ref name="Hugot"/>
Some suspect that inflammation in IBD is due to increased permeability of the inner lining of the colon, which may allow bacteria to invade the tissues and cause an immune reaction that leads prolonged inflammation.<ref name="Steinhoff"/><ref name="Suenaert"/> Abnormal [[tight junction]]s, which are supposed to prevent permeability, have been found in cells of patients with IBD.<ref name="Suenaert"/> Because of the potentially harmful role of these bacteria, antibiotics are frequently prescribed to treat Crohn’s disease.<ref name="Keeley"/> However, inflammation could occur first and cause the increased intestinal permeability found in diseases such as Crohn's, so the causative role of bacteria is not clear.<ref name="Suenaert"/>
===Colitis===
It has been suggested that commensal bacteria are responsible for the development of [[colitis]], since mice raised in a [[aseptic|sterile]] environment do not get the disease.<ref name="Veltkamp">Veltkamp C, Tonkonogy SL, De Jong YP, Albright C, Grenther WB, Balish E, Terhorst C, and Sartor RB. 2001. Continuous stimulation by normal luminal bacteria is essential for the development and perpetuation of colitis in Tg(epsilon26) mice. ''Gastroenterology'', Volume 120, Issue 4, Pages 900-913. PMID 11231944. Accessed [[September 7]], [[2007]]</ref> However, while some bacterial strains such as ''C. difficile''<ref name="Guarner and Malagelada, 2003a"/> and even normal gut bacteria cause colitis,<ref name="Veltkamp"/> others prevent the disease in mice.<ref name="Guarner and Malagelada, 2003a"/>
===Obesity===
It is known from experiments on mice that obese mice lacking leptin, a lipid metabolism regulator (ob/ob mice), have a distinct gut flora compared to (normal) lean mice, reflected in a change in the ratio between bacteria from the divisions [[bacteroidetes]] and [[firmicutes]], which is shifted towards less [[bacteroidetes]] and more [[firmicutes]] in obese mice.
The microbes occupying the human gut are also in direct relation to [[obesity]]. A shift in the ratio between bacterial-divisions [[firmicutes]] and [[bacteroidetes]] can be observed in lean and obese individuals – in latter a shift towards firmicutes can be observed. The ratio between [[firmicutes]] and [[bacteroidetes]] dynamically reflects the overall weight-condition of an individual, shifting towards bacteroides if an obese individual loses weight.
The mutual influence of gut flora composition and weight-condition is connected to differences in the energy-resorption potential of different ratios of firmicutes and bacteroidetes, especially in the digestion of fatty acids and dietary polysaccharides, as shown by experiments wherein the (caecum) gut flora of obese mice was transplanted into germ free recipient mice, leading to an increase in weight despite a decrease in food consumption.<ref name="Ley, et al.">Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. ''Nature'', 2006 Volume 444, Issue 7122, Pages 1022-1023. PMID 17183309. Accessed [[September 7]], [[2007]]</ref><ref name="Turnbaugh, et al.">Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. 2006. An obesity-associated gut microbiome with increased capacity for energy harvest. ''Nature'', Volume 444, Issue 7122, Pages 1027-1031. PMID 17183312. Accessed [[September 7]], [[2007]]</ref><ref name="Bäckhed, et al.">Bäckhed F, Manchester JK, Semenkovich CF, Gordon JI. 2007. [http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17210919 Mechanisms underlying the resistance to diet-induced obesity in germ-free mice.] ''Proceedings of the National Academy of Sciences of the USA'', Volume 104, Issue 3, Pages 979-984. PMID 17210919. Accessed [[September 7]], [[2007]]</ref><ref name="Bäckhed F, et al.">Bäckhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, Semenkovich CF, Gordon JI. [http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=15505215 The gut microbiota as an environmental factor that regulates fat storage.] ''Proceedings of the National Academy of Sciences of the USA'', Volume 101, Issue 44, Pages 15718-15723. PMID 15505215. Accessed [[September 7]], [[2007]]</ref>
==Sources and notes==
{{Reflist|2}}
[[Category:Bacteriology]]
[[Category:Digestive system]]
[[Category:Firmicutes]]
[[Category:Gut flora|*]]
[[Category:Microbiology]]
[[Category:Environmental microbiology]]
[[bg:Чревна микрофлора]]
[[cs:Střevní mikroflóra]]
[[de:Darmflora]]
[[es:Flora intestinal]]
[[fr:Flore intestinale]]
[[hu:Bélflóra]]
[[lt:Žarnyno mikroflora]]
[[nl:Darmflora]]
[[pl:Flora bakteryjna jelita]]
[[pt:Flora intestinal]]
[[fi:Normaalifloora]]
[[sv:Tarmflora]]
[[tr:Bağırsak florası]]
[[uk:Флора кишечника]]