Gut flora
Encyclopedia
The human body
Human body
The human body is the entire structure of a human organism, and consists of a head, neck, torso, two arms and two legs.By the time the human reaches adulthood, the body consists of close to 100 trillion cells, the basic unit of life...
, consisting of about 100 trillion cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
, carries about ten times as many microorganisms in the intestine
Intestine
In human anatomy, the intestine is the segment of the alimentary canal extending from the pyloric sphincter of the stomach to the anus and, in humans and other mammals, consists of two segments, the small intestine and the large intestine...
s. The metabolic activities performed by these bacteria resemble those of an organ, leading some to liken gut bacteria to a "forgotten" organ. It is estimated that these gut flora have around 100 times as many gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s in aggregate as there are in the human genome
Human genome
The human genome is the genome of Homo sapiens, which is stored on 23 chromosome pairs plus the small mitochondrial DNA. 22 of the 23 chromosomes are autosomal chromosome pairs, while the remaining pair is sex-determining...
.
Bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
make up most of the flora in the colon
Colon (anatomy)
The colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a...
and up to 60% of the dry mass of feces
Feces
Feces, faeces, or fæces is a waste product from an animal's digestive tract expelled through the anus or cloaca during defecation.-Etymology:...
. Somewhere between 300 and 1000 different species
Species
In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are...
live in the gut, with most estimates at about 500. However, it is probable that 99% of the bacteria come from about 30 or 40 species. Fungi and protozoa
Protozoa
Protozoa are a diverse group of single-cells eukaryotic organisms, many of which are motile. Throughout history, protozoa have been defined as single-cell protists with animal-like behavior, e.g., movement...
also make up a part of the gut flora, but little is known about their activities.
Research suggests that the relationship between gut flora
Flora (microbiology)
In microbiology, flora refers to the collective bacteria and other microorganisms in an ecosystem . While the term microflora is widely used, it is technically a misnomer since the word root flora pertains to the kingdom plantae...
and humans is not merely commensal
Commensalism
In ecology, commensalism is a class of relationship between two organisms where one organism benefits but the other is neutral...
(a non-harmful coexistence), but rather a symbiotic relationship. Though people can survive without gut flora, the microorganisms perform a host of useful functions, such as fermenting
Fermentation (biochemistry)
Fermentation is the process of extracting energy from the oxidation of organic compounds, such as carbohydrates, using an endogenous electron acceptor, which is usually an organic compound. In contrast, respiration is where electrons are donated to an exogenous electron acceptor, such as oxygen,...
unused energy substrates, training the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
, preventing growth of harmful, pathogenic bacteria, regulating the development of the gut, producing vitamins for the host (such as biotin
Biotin
Biotin, also known as Vitamin H or Coenzyme R, is a water-soluble B-complex vitamin discovered by Bateman in 1916. It is composed of a ureido ring fused with a tetrahydrothiophene ring. A valeric acid substituent is attached to one of the carbon atoms of the tetrahydrothiophene ring...
and vitamin K
Vitamin K
Vitamin K is a group of structurally similar, fat soluble vitamins that are needed for the posttranslational modification of certain proteins required for blood coagulation and in metabolic pathways in bone and other tissue. They are 2-methyl-1,4-naphthoquinone derivatives...
), and producing hormones to direct the host to store fats. However, in certain conditions, some species are thought to be capable of causing disease
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
by producing infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
or increasing cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
risk for the host.
Over 99% of the bacteria in the gut are anaerobes, but in the cecum
Cecum
The cecum or caecum is a pouch, connecting the ileum with the ascending colon of the large intestine. It is separated from the ileum by the ileocecal valve or Bauhin's valve, and is considered to be the beginning of the large intestine. It is also separated from the colon by the cecocolic...
, aerobic bacteria reach high densities.
Types
Human microbiome project
The Human Microbiome Project is a United States National Institutes of Health initiative with the goal of identifying and characterizing the microorganisms which are found in association with both healthy and diseased humans . Launched in 2008, it is a five-year project, best characterized as a...
. In 2009, scientists from INRA (France) highlighted the existence of a small number of species shared by all individuals constituting the human intestinal microbiota phylogenetic core .
Most bacteria belong to the genera Bacteroides
Bacteroides
Bacteroides is a genus of Gram-negative, bacillus bacteria. Bacteroides species are non-endospore-forming, anaerobes, and may be either motile or non-motile, depending on the species. The DNA base composition is 40-48% GC. Unusual in bacterial organisms, Bacteroides membranes contain sphingolipids...
, Clostridium
Clostridium
Clostridium is a genus of Gram-positive bacteria, belonging to the Firmicutes. They are obligate anaerobes capable of producing endospores. Individual cells are rod-shaped, which gives them their name, from the Greek kloster or spindle...
, Fusobacterium
Fusobacterium
Fusobacterium is a genus of filamentous, anaerobic, Gram-negative bacteria, similar to Bacteroides.Fusobacterium contribute to several human diseases, including periodontal diseases, Lemierre's syndrome, and topical skin ulcers...
, Eubacterium, Ruminococcus
Ruminococcus
Ruminococcus is a genus of bacteria in the class Clostridia. They are anaerobic, gram-positive gut microbes. One or more species in this genus are found in significant numbers in the intestines of humans. The type species is R. flavefaciens...
, Peptococcus, Peptostreptococcus
Peptostreptococcus
Peptostreptococcus is a genus of anaerobic, Gram-positive, non-spore forming bacteria. The cells are small, spherical, and can occur in short chains, in pairs or individually. Peptostreptococcus are slow-growing bacteria with increasing resistance to antimicrobial drugs.The most frequently...
, and Bifidobacterium
Bifidobacterium
Bifidobacterium is a genus of Gram-positive, non-motile, often branched anaerobic bacteria. They are ubiquitous, endosymbiotic inhabitants of the gastrointestinal tract, vagina and mouth of mammals and other animals. Bifidobacteria are one of the major genera of bacteria that make up the colon...
. Other genera, such as Escherichia
Escherichia
Escherichia is a genus of Gram-negative, non-spore forming, facultatively anaerobic, rod-shaped bacteria from the family Enterobacteriaceae. In those species which are inhabitants of the gastrointestinal tracts of warm-blooded animals, Escherichia species provide a portion of the...
and Lactobacillus
Lactobacillus
Lactobacillus is a genus of Gram-positive facultative anaerobic or microaerophilic rod-shaped bacteria. They are a major part of the lactic acid bacteria group, named as such because most of its members convert lactose and other sugars to lactic acid. They are common and usually benign...
, are present to a lesser extent. Species from the genus Bacteroides alone constitute about 30% of all bacteria in the gut, suggesting that this genus is especially important in the functioning of the host.
The currently known genera of fungi of the gut flora include Candida
Candida (genus)
Candida is a genus of yeasts. Many species are harmless commensals or endosymbionts of animal hosts including humans, but other species, or harmless species in the wrong location, can cause disease. Candida albicans can cause infections in humans and other animals, especially in immunocompromised...
, Saccharomyces
Saccharomyces
Saccharomyces is a genus in the kingdom of fungi that includes many species of yeast. Saccharomyces is from Greek σάκχαρ and μύκης and means sugar fungus. Many members of this genus are considered very important in food production. One example is Saccharomyces cerevisiae, which is used in making...
, Aspergillus
Aspergillus
Aspergillus is a genus consisting of several hundred mold species found in various climates worldwide. Aspergillus was first catalogued in 1729 by the Italian priest and biologist Pier Antonio Micheli...
, and Penicillium
Penicillium
Penicillium is a genus of ascomycetous fungi of major importance in the natural environment as well as food and drug production. Members of the genus produce penicillin, a molecule that is used as an antibiotic, which kills or stops the growth of certain kinds of bacteria inside the body...
.
An enterotype
Enterotype
An enterotype is a classification of living organisms based on its bacteriological ecosystem in the human gut microbiome. The discovery of three human enterotypes was announced in the April 2011 issue of Nature by Peer Bork and his associates....
is a classification of living organisms based on its bacteriological ecosystem
Ecosystem
An ecosystem is a biological environment consisting of all the organisms living in a particular area, as well as all the nonliving , physical components of the environment with which the organisms interact, such as air, soil, water and sunlight....
in the human gut microbiome. Three human enterotypes have been discovered.
Acquisition of gut flora in human infants
The gastrointestinal tractGastrointestinal tract
The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
of a normal fetus
Fetus
A fetus is a developing mammal or other viviparous vertebrate after the embryonic stage and before birth.In humans, the fetal stage of prenatal development starts at the beginning of the 11th week in gestational age, which is the 9th week after fertilization.-Etymology and spelling variations:The...
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 may have bacterial strains derived from the mothers' feces
Feces
Feces, faeces, or fæces is a waste product from an animal's digestive tract expelled through the anus or cloaca during defecation.-Etymology:...
in the upper gastrointestinal tract. Infants born by caesarean section
Caesarean section
A Caesarean section, is a surgical procedure in which one or more incisions are made through a mother's abdomen and uterus to deliver one or more babies, or, rarely, to remove a dead fetus...
may also be exposed to their mothers' microflora, but the initial exposure is most likely to be from the surrounding environment such as the air, other infants, and the nursing staff, which serve as vectors for transfer. The primary gut flora in infants born by caesarean delivery may be disturbed for up to six months after birth, whereas vaginally born infants take up to one month for their intestinal microflora to be well established. 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 108 to 1010 per gram of feces
Feces
Feces, faeces, or fæces is a waste product from an animal's digestive tract expelled through the anus or cloaca during defecation.-Etymology:...
. During the first week of life, these bacteria create a reducing environment favorable for the subsequent bacterial succession
Ecological succession
Ecological succession, is the phenomenon or process by which a community progressively transforms itself until a stable community is formed. It is a fundamental concept in ecology, and refers to more or less predictable and orderly changes in the composition or structure of an ecological community...
of strict anaerobic species
Anaerobic organism
An anaerobic organism or anaerobe is any organism that does not require oxygen for growth. It could possibly react negatively and may even die if oxygen is present...
mainly belonging to the genera Bifidobacterium
Bifidobacterium
Bifidobacterium is a genus of Gram-positive, non-motile, often branched anaerobic bacteria. They are ubiquitous, endosymbiotic inhabitants of the gastrointestinal tract, vagina and mouth of mammals and other animals. Bifidobacteria are one of the major genera of bacteria that make up the colon...
, Bacteroides
Bacteroides
Bacteroides is a genus of Gram-negative, bacillus bacteria. Bacteroides species are non-endospore-forming, anaerobes, and may be either motile or non-motile, depending on the species. The DNA base composition is 40-48% GC. Unusual in bacterial organisms, Bacteroides membranes contain sphingolipids...
, Clostridium
Clostridium
Clostridium is a genus of Gram-positive bacteria, belonging to the Firmicutes. They are obligate anaerobes capable of producing endospores. Individual cells are rod-shaped, which gives them their name, from the Greek kloster or spindle...
, and Ruminococcus
Ruminococcus
Ruminococcus is a genus of bacteria in the class Clostridia. They are anaerobic, gram-positive gut microbes. One or more species in this genus are found in significant numbers in the intestines of humans. The type species is R. flavefaciens...
. Breast-fed
Weaning
Weaning is the process of gradually introducing a mammal infant, either human or animal, to what will be its adult diet and withdrawing the supply of its mother's milk.The process takes place only in mammals, as only mammals produce milk...
babies become dominated by bifidobacteria, possibly due to the contents of bifidobacterial growth factors
Bifidus Factor
A Bifidus factor is a compound that specifically enhances the growth of bifidobacteria in either a product or in the intestines of humans and/or animals. Several products have been marketed as bifidogenic factors, such as several prebiotics and methyl-N-acetyl D-glucosamine in human milk . The...
in breast milk. In contrast, the microbiota of formula-fed
Infant formula
Infant formula is a manufactured food designed and marketed for feeding to babies and infants under 12 months of age, usually prepared for bottle-feeding or cup-feeding from powder or liquid . The U.S...
infants is more diverse, with high numbers of Enterobacteriaceae
Enterobacteriaceae
The Enterobacteriaceae is a large family of bacteria that includes many of the more familiar pathogens, such as Salmonella, Escherichia coli, Yersinia pestis, Klebsiella and Shigella. This family is the only representative in the order Enterobacteriales of the class Gammaproteobacteria in the...
, enterococci, bifidobacteria, Bacteroides
Bacteroides
Bacteroides is a genus of Gram-negative, bacillus bacteria. Bacteroides species are non-endospore-forming, anaerobes, and may be either motile or non-motile, depending on the species. The DNA base composition is 40-48% GC. Unusual in bacterial organisms, Bacteroides membranes contain sphingolipids...
, and clostridia
Clostridium
Clostridium is a genus of Gram-positive bacteria, belonging to the Firmicutes. They are obligate anaerobes capable of producing endospores. Individual cells are rod-shaped, which gives them their name, from the Greek kloster or spindle...
. By the second year of life, the fecal microflora resemble that of adults.
Functions
Bacteria in the gut fulfill a host of useful functions for humans, including digestion of unutilized energy substrates, stimulating cell growth, repressing the growth of harmful microorganisms, training the immune system to respond only to pathogenPathogen
A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...
s, and defending against some diseases.
Carbohydrate fermentation and absorption
Without gut flora, the human body would be unable to utilize some of the undigested carbohydrateCarbohydrate
A carbohydrate is an organic compound with the empirical formula ; that is, consists only of carbon, hydrogen, and oxygen, with a hydrogen:oxygen atom ratio of 2:1 . However, there are exceptions to this. One common example would be deoxyribose, a component of DNA, which has the empirical...
s it consumes, because some types of gut flora have enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s that human cells lack for breaking down certain polysaccharide
Polysaccharide
Polysaccharides are long carbohydrate molecules, of repeated monomer units joined together by glycosidic bonds. They range in structure from linear to highly branched. Polysaccharides are often quite heterogeneous, containing slight modifications of the repeating unit. Depending on the structure,...
s. Rodents raised in a sterile environment and lacking in gut flora need to eat 30% more calories just to remain the same weight as their normal counterparts. Carbohydrates that humans cannot digest
Digestion
Digestion is the mechanical and chemical breakdown of food into smaller components that are more easily absorbed into a blood stream, for instance. Digestion is a form of catabolism: a breakdown of large food molecules to smaller ones....
without bacterial help include certain starches, fiber, oligosaccharides and sugar
Sugar
Sugar is a class of edible crystalline carbohydrates, mainly sucrose, lactose, and fructose, characterized by a sweet flavor.Sucrose in its refined form primarily comes from sugar cane and sugar beet...
s that the body failed to digest and absorb like lactose
Lactose
Lactose is a disaccharide sugar that is found most notably in milk and is formed from galactose and glucose. Lactose makes up around 2~8% of milk , although the amount varies among species and individuals. It is extracted from sweet or sour whey. The name comes from or , the Latin word for milk,...
in the case of lactose intolerance
Lactose intolerance
Lactose intolerance, also called lactase deficiency or hypolactasia, is the inability to digest and metabolize lactose, a sugar found in milk...
and sugar alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
s, mucus
Mucus
In vertebrates, mucus is a slippery secretion produced by, and covering, mucous membranes. Mucous fluid is typically produced from mucous cells found in mucous glands. Mucous cells secrete products that are rich in glycoproteins and water. Mucous fluid may also originate from mixed glands, which...
produced by the gut, and proteins. A further result is flatulence
Flatulence
Flatulence is the expulsion through the rectum of a mixture of gases that are byproducts of the digestion process of mammals and other animals. The medical term for the mixture of gases is flatus, informally known as a fart, or simply gas...
, specifically due to the metabolism of oligosaccharide
Oligosaccharide
An oligosaccharide is a saccharide polymer containing a small number of component sugars, also known as simple sugars...
s (notably from bean
Bean
Bean is a common name for large plant seeds of several genera of the family Fabaceae used for human food or animal feed....
s) by many different species.
Bacteria turn carbohydrates they ferment into short chain fatty acid
Short chain fatty acid
Short-chain fatty acids are a sub-group of fatty acids with aliphatic tails of less than six carbons. They include:* Acetic acid* Propionic acid* Isobutyric acid * Butyric acid* Isovaleric acid...
s, or SCFAs, by a form of fermentation called saccharolytic fermentation. Products include acetic acid
Acetic acid
Acetic acid is an organic compound with the chemical formula CH3CO2H . It is a colourless liquid that when undiluted is also called glacial acetic acid. Acetic acid is the main component of vinegar , and has a distinctive sour taste and pungent smell...
, propionic acid
Propionic acid
Propanoic acid is a naturally occurring carboxylic acid with chemical formula CH3CH2COOH. It is a clear liquid with a pungent odor...
and butyric acid
Butyric acid
Butyric acid , also known under the systematic name butanoic acid, is a carboxylic acid with the structural formula CH3CH2CH2-COOH. Salts and esters of butyric acid are known as butyrates or butanoates...
. These materials can be used by host cells, providing a major source of useful energy and nutrients for humans, as well as helping the body to absorb essential dietary minerals such as calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
, magnesium
Magnesium
Magnesium is a chemical element with the symbol Mg, atomic number 12, and common oxidation number +2. It is an alkaline earth metal and the eighth most abundant element in the Earth's crust and ninth in the known universe as a whole...
and iron
Iron
Iron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...
. Gases and organic acid
Organic acid
An organic acid is an organic compound with acidic properties. The most common organic acids are the carboxylic acids, whose acidity is associated with their carboxyl group –COOH. Sulfonic acids, containing the group –SO2OH, are relatively stronger acids. The relative stability of the conjugate...
s, such as lactic acid
Lactic acid
Lactic acid, also known as milk acid, is a chemical compound that plays a role in various biochemical processes and was first isolated in 1780 by the Swedish chemist Carl Wilhelm Scheele. Lactic acid is a carboxylic acid with the chemical formula C3H6O3...
, are also produced by saccharolytic fermentation. Acetic acid is used by muscle
Muscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...
, propionic acid helps the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
produce ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
, and butyric acid provides energy to gut cells and may prevent cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
. Evidence also indicates that bacteria enhance the absorption and storage of lipids and produce and then facilitate the body to absorb needed vitamins like vitamin K
Vitamin K
Vitamin K is a group of structurally similar, fat soluble vitamins that are needed for the posttranslational modification of certain proteins required for blood coagulation and in metabolic pathways in bone and other tissue. They are 2-methyl-1,4-naphthoquinone derivatives...
.
Another, less favorable type of fermentation, proteolytic fermentation, breaks down proteins like enzymes, dead host and bacterial cells, and collagen
Collagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
and elastin
Elastin
Elastin is a protein in connective tissue that is elastic and allows many tissues in the body to resume their shape after stretching or contracting. Elastin helps skin to return to its original position when it is poked or pinched. Elastin is also an important load-bearing tissue in the bodies of...
found in food, and can produce toxins and carcinogen
Carcinogen
A carcinogen is any substance, radionuclide, or radiation that is an agent directly involved in causing cancer. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes...
s in addition to SCFAs. Thus, a diet lower in protein reduces exposure to toxins.
Beneficial flora increase the gut's absorption of water, reduce counts of damaging bacteria, increase growth of human gut cells, and stimulate growth of indigenous bacteria.
Trophic effects
Another benefit of SCFAs is that they increase growth of intestinal epithelial cells and control their proliferation and differentiation. They may also cause lymphoid tissue near the gut to grow. Bacterial cells also alter intestinal growth by changing the expression of cell surface proteins such as sodium/glucose transporters. In addition, changes they make to cells may prevent injury to the gut mucosa from occurring.Repression of pathogenic microbial growth
Yeast
Yeasts are eukaryotic micro-organisms classified in the kingdom Fungi, with 1,500 species currently described estimated to be only 1% of all fungal species. Most reproduce asexually by mitosis, and many do so by an asymmetric division process called budding...
s and bacterial species such as Clostridium difficile
Clostridium difficile
Clostridium difficile , also known as "CDF/cdf", or "C...
(the overgrowth of which can cause pseudomembranous colitis
Pseudomembranous colitis
Pseudomembranous colitis, a cause of antibiotic-associated diarrhea , is an infection of the colon. It is often, but not always, caused by the bacterium Clostridium difficile. Because of this, the informal name C. difficile colitis is also commonly used. The illness is characterized by...
) are unable to grow excessively due to competition from helpful gut flora species adhering to the mucosal lining of the intestine, thus animals without gut flora are infected
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
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.
Helpful bacteria prevent the growth of pathogenic species by competing for nutrition and attachment sites to the epithelium
Epithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...
of the colon. Symbiotic bacteria are more at home in this ecological niche and are thus more successful in the competition. Indigenous gut floras also produce bacteriocins, which are proteinaceous toxins that inhibit growth of similar bacterial strains, substances that kill harmful microbes and the levels of which can be regulated by enzymes produced by the host.
The process of fermentation, since it produces lactic acid and different fatty acid
Fatty acid
In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...
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.
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.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
Weaning
Weaning is the process of gradually introducing a mammal infant, either human or animal, to what will be its adult diet and withdrawing the supply of its mother's milk.The process takes place only in mammals, as only mammals produce milk...
from predominantly facultative anaerobic species, such as Streptococci and Escherichia coli
Escherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
, to mostly obligate anaerobic species.
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
Radiation
In physics, radiation is a process in which energetic particles or energetic waves travel through a medium or space. There are two distinct types of radiation; ionizing and non-ionizing...
. TLRs are one of the two classes of pattern-recognition receptors (PRR) that provide the intestine the ability to discriminate between the pathogenic and commensal bacteria. These PRRs identify the pathogens that have crossed the mucosal barriers and trigger a set of responses that take action against the pathogen, which involve three main immunosensory cells: surface enterocytes, M cells and dendritic cells.
The other class of PRRs are known as the nucleotide-binding oligomerization domain/caspase recruitment domain isoforms (NOD/CARD), which are cytoplasmic proteins that recognize endogenous or microbial molecules or stress responses and forms oligomers that activate inflammatory caspases. This would result in the cleavage and activation of important inflammatory cytokines and/or activate NF-κB signaling pathway to induce the production of inflammatory molecules.
Bacteria can influence the phenomenon known as oral tolerance, in which the immune system is less sensitive to an antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
(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 allergies
Allergy
An Allergy is a hypersensitivity disorder of the immune system. Allergic reactions occur when a person's immune system reacts to normally harmless substances in the environment. A substance that causes a reaction is called an allergen. These reactions are acquired, predictable, and rapid...
and auto-immune disease.
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.
Metabolic function
The resident gut microflora positively control the intestinal epithelial cell differentiation and proliferation through the production of short-chain fatty acids. They also mediate other metabolic effects such as the syntheses of vitamins like biotin and folate, as well as absorption of ions including magnesium, calcium and iron.The gut flora plays a major role in metabolizing dietary carcinogens, the microcomponents and the macrocomponents. The microcomponents are genotoxic, and the major focus is on recent advances in heterocyclic amines (HCAs), which are produced by cooking proteinaceous food, such as meat and fish, which can then induce tumors in organs like the breast, colon and prostate. HCAs are naturally occurring; therefore, the complete avoidance of them is impractical, which is why the metabolic function of gut flora of such components is of great importance to our body, as this would help in prevention of such tumors that are difficult to avoid. The macrocomponents consists of the excessive intake of fat and sodium chloride, which can later promote tumors, such as in breasts and colons, from fat and gastric carcinogenesis from sodium chloride.
Preventing allergy
Bacteria are also implicated in preventing allergiesAllergy
An Allergy is a hypersensitivity disorder of the immune system. Allergic reactions occur when a person's immune system reacts to normally harmless substances in the environment. A substance that causes a reaction is called an allergen. These reactions are acquired, predictable, and rapid...
, an overreaction of the immune system to non-harmful antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
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 C. difficile
Clostridium difficile
Clostridium difficile , also known as "CDF/cdf", or "C...
and S. aureus and lower prevalence of Bacteroides and Bifidobacteria. 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 that overreacts to antigens. On the other hand, the differences in flora could be a result, not a cause, of the allergies.
Preventing inflammatory bowel disease
Another indicator that bacteria help train the immune system is the epidemiologyEpidemiology
Epidemiology is the study of health-event, health-characteristic, or health-determinant patterns in a population. It is the cornerstone method of public health research, and helps inform policy decisions and evidence-based medicine by identifying risk factors for disease and targets for preventive...
of Inflammatory Bowel Disease
Inflammatory bowel disease
In medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...
, or IBD, such as Crohn's Disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...
(CD). Some authors suggest that SCFAs prevent IBD. In addition, some forms of bacteria can prevent inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
. The incidence and prevalence of IBD is high in industrialized countries with a high standard of living
Standard of living
Standard of living is generally measured by standards such as real income per person and poverty rate. Other measures such as access and quality of health care, income growth inequality and educational standards are also used. Examples are access to certain goods , or measures of health such as...
and low in 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. Its incidence is inversely linked with poor sanitation during the first years of life and consumption of fruits, vegetables, and unprocessed foods. Also, the use of antibiotics, which kill native gut flora and harmful infectious pathogens alike, especially during childhood, is associated with inflammatory bowel disease. On the other hand, using probiotic
Probiotic
Probiotics are live microorganisms thought to be beneficial to the host organism. According to the currently adopted definition by FAO/WHO, probiotics are: "Live microorganisms which when administered in adequate amounts confer a health benefit on the host"...
s, bacteria consumed as part of the diet that impart health benefits (aside from just nutrition
Nutrition
Nutrition is the provision, to cells and organisms, of the materials necessary to support life. Many common health problems can be prevented or alleviated with a healthy diet....
), helps treat IBD.
Effects of antibiotic use
Altering the numbers of gut bacteria, for example by taking broad-spectrum antibioticBroad-spectrum antibiotic
The term broad-spectrum antibiotic refers to an antibiotic that acts against a wide range of disease-causing bacteria. A broad-spectrum antibiotic acts against both Gram-positive and Gram-negative bacteria, in contrast to a narrow-spectrum antibiotic, which is effective against specific families of...
s, may affect the host's health and ability to digest food. People may take the drugs to cure bacterial illnesses or may unintentionally consume significant amounts of antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
s by eating the meat of animals to which they were fed. Antibiotics can cause antibiotic-associated diarrhea
Antibiotic-associated diarrhea
Antibiotic-associated diarrhea results from an imbalance in the colonic microbiota caused by antibiotic therapy. Microbiota alteration changes carbohydrate metabolism with decreased short-chain fatty acid absorption and an osmotic diarrhea as a result...
(AAD) by irritating the bowel directly, changing the levels of gut flora, or allowing pathogen
Pathogen
A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...
ic bacteria to grow. 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.
Changing the numbers and species of gut flora can reduce the body's ability to ferment carbohydrates and metabolize bile
Bile
Bile or gall is a bitter-tasting, dark green to yellowish brown fluid, produced by the liver of most vertebrates, that aids the process of digestion of lipids in the small intestine. In many species, bile is stored in the gallbladder and upon eating is discharged into the duodenum...
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.
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.
Gut flora composition also changes in severe illnesses, due not only to antibiotic use but also to such factors as ischemia
Ischemia
In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...
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 re-establishment of healthy ones.
Pharmabiotics
Pharmabiotics is a generic term to encompass any form of therapeutic exploitation of the commensal flora, including the use of live probiotic bacteria, probiotic-derived biologically active metabolites, prebiotics, synbioticsSynbiotics
Synbiotics refer to nutritional supplements combining probiotics and prebiotics in a form of synergism, hence synbiotics.Probiotics are live bacteria which are intended to colonize the large intestine and confer physiological health benefits to the host...
or genetically modified commensal bacteria. Since the lack of gut flora can have such harmful health effects, the use of probiotics has anti-inflammatory
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
effects in the gut and may be useful for improving health. Prebiotics
Prebiotic (nutrition)
Prebiotics are non-digestible food ingredients that stimulate the growth and/or activity of bacteria in the digestive system in ways claimed to be beneficial to health. They were first identified and named by Marcel Roberfroid in 1995. As a functional food component, prebiotics, like probiotics,...
are dietary components that can help foster the growth of micro-organisms in the gut, which may lead to better health. There is evidence supporting a therapeutic role for probiotic strategies for treating mucosal inflammatory disorders such as IBD, atopy, infection, diarrhoea, cancer and arthritis.
Role in disease
Bacteria in the digestive tract have pathogenic properties in addition to their health-inducing ones: they can produce toxinToxin
A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...
s and carcinogen
Carcinogen
A carcinogen is any substance, radionuclide, or radiation that is an agent directly involved in causing cancer. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes...
s and have been implicated in such conditions as multisystem organ failure, sepsis
Sepsis
Sepsis is a potentially deadly medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection. The body may develop this inflammatory response by the immune system to microbes in the blood, urine, lungs, skin, or other tissues...
, colon cancer, and inflammatory bowel disease
Inflammatory bowel disease
In medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...
(IBD). 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
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s to regulate this balance.
Cancer
Some generaGenus
In biology, a genus is a low-level taxonomic rank used in the biological classification of living and fossil organisms, which is an example of definition by genus and differentia...
of bacteria, such as Bacteroides and Clostridium, have been associated with an increase in tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
growth rate, while other genera, such as Lactobacillus
Lactobacillus
Lactobacillus is a genus of Gram-positive facultative anaerobic or microaerophilic rod-shaped bacteria. They are a major part of the lactic acid bacteria group, named as such because most of its members convert lactose and other sugars to lactic acid. They are common and usually benign...
and Bifidobacteria, are known to prevent tumor formation.
Translocation
Helpful bacteria can be very harmful to the host if they get outside of the intestinal tract. TranslocationTranslocation
Translocation may refer to:* Chromosomal translocation, in genetics* Translocation in plants, transport of food or pesticides through phloem or xylem* Protein translocation or protein targeting, a process in protein biosynthesis...
, which occurs when bacteria leave the gut through its mucosal lining, the border between the lumen
Lumen (anatomy)
A lumen in biology is the inside space of a tubular structure, such as an artery or intestine...
of the gut and the inside of the body, can occur in a number of different diseases. It can be caused by too much growth of bacteria in the small intestine, reduced immunity of the host, or increased gut lining permeability. The gut can become more permeable in diseases like cirrhosis
Cirrhosis
Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrosis, scar tissue and regenerative nodules , leading to loss of liver function...
, which is damaging due in part to the activity of gut flora.
If the gut is perforated, bacteria can invade the body, causing a potentially fatal infection. Aerobic bacteria can make an infection worse by using up all available oxygen and creating an environment favorable to anaerobes.
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 the entire gut flora together or some specific types.It has been noted that though Ulcerative Colitis
Ulcerative colitis
Ulcerative colitis is a form of inflammatory bowel disease . Ulcerative colitis is a form of colitis, a disease of the colon , that includes characteristic ulcers, or open sores. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset...
and Crohn's disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...
(two types of IBD) probably have genetic
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
components, they are not inherited in a Mendelian
Mendelian inheritance
Mendelian inheritance is a scientific description of how hereditary characteristics are passed from parent organisms to their offspring; it underlies much of genetics...
fashion and are thus probably due to a complex set of factors rather than solely to a gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. Though neither bacterial colonization nor genetics
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
is sufficient to cause the disease, bacteria probably play a role in these disorders.
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 to prolonged inflammation. Tissue damage in IBD results from the immunological misperception of danger within the naturally occurring flora or due to failure of normal tolerance to pathogenic bacteria. It is still unclear whether the inflammation that occurs is due to a specific subset of intestinal microbes or due to a problem with the tolerance of commensal gut flora. Abnormal tight junction
Tight junction
Tight junctions, or zonula occludens, are the closely associated areas of two cells whose membranes join together forming a virtually impermeable barrier to fluid. It is a type of junctional complex present only in vertebrates...
s, which are supposed to prevent permeability, have been found in cells of patients with IBD. Because of the potentially harmful role of these bacteria, antibiotics are frequently prescribed to treat Crohn’s disease. 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. Conventional therapies for IBD primarily target the mucosal inflammatory responses by using pharmabiotics.
Colitis
It has been suggested that commensal bacteria are responsible for the development of colitisColitis
In medicine, colitis refers to an inflammation of the colon and is often used to describe an inflammation of the large intestine .Colitides may be acute and self-limited or chronic, i.e...
, since mice raised in a sterile environment do not get the disease. However, while some bacterial strains such as C. difficile and even normal gut bacteria cause colitis, others prevent the disease in mice.
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 BacteroidetesBacteroidetes
The phylum Bacteroidetes is composed of three large classes of bacteria that are widely distributed in the environment, including in soil, in sediments, sea water and in the guts and on the skin of animals....
and Firmicutes
Firmicutes
The Firmicutes are a phylum of bacteria, most of which have Gram-positive cell wall structure. A few, however, such as Megasphaera, Pectinatus, Selenomonas and Zymophilus, have a porous pseudo-outer-membrane that causes them to stain Gram-negative...
, which is shifted towards fewer Bacteroidetes
Bacteroidetes
The phylum Bacteroidetes is composed of three large classes of bacteria that are widely distributed in the environment, including in soil, in sediments, sea water and in the guts and on the skin of animals....
and more Firmicutes
Firmicutes
The Firmicutes are a phylum of bacteria, most of which have Gram-positive cell wall structure. A few, however, such as Megasphaera, Pectinatus, Selenomonas and Zymophilus, have a porous pseudo-outer-membrane that causes them to stain Gram-negative...
in obese mice.
The microbes occupying the human gut are also in direct relation to obesity
Obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
. A shift in the ratio between bacterial divisions Firmicutes
Firmicutes
The Firmicutes are a phylum of bacteria, most of which have Gram-positive cell wall structure. A few, however, such as Megasphaera, Pectinatus, Selenomonas and Zymophilus, have a porous pseudo-outer-membrane that causes them to stain Gram-negative...
and Bacteroidetes
Bacteroidetes
The phylum Bacteroidetes is composed of three large classes of bacteria that are widely distributed in the environment, including in soil, in sediments, sea water and in the guts and on the skin of animals....
can be observed in lean and obese individuals—in the latter, a shift towards Firmicutes
Firmicutes
The Firmicutes are a phylum of bacteria, most of which have Gram-positive cell wall structure. A few, however, such as Megasphaera, Pectinatus, Selenomonas and Zymophilus, have a porous pseudo-outer-membrane that causes them to stain Gram-negative...
can be observed. The ratio between Firmicutes
Firmicutes
The Firmicutes are a phylum of bacteria, most of which have Gram-positive cell wall structure. A few, however, such as Megasphaera, Pectinatus, Selenomonas and Zymophilus, have a porous pseudo-outer-membrane that causes them to stain Gram-negative...
and Bacteroidetes
Bacteroidetes
The phylum Bacteroidetes is composed of three large classes of bacteria that are widely distributed in the environment, including in soil, in sediments, sea water and in the guts and on the skin of animals....
dynamically reflects the overall weight condition of an individual, shifting towards Bacteroidetes
Bacteroidetes
The phylum Bacteroidetes is composed of three large classes of bacteria that are widely distributed in the environment, including in soil, in sediments, sea water and in the guts and on the skin of animals....
if an obese individual loses weight.
The mutual influence of gut flora composition and weight condition is connected to differences in the energy-reabsorbing potential of different ratios of Firmicutes
Firmicutes
The Firmicutes are a phylum of bacteria, most of which have Gram-positive cell wall structure. A few, however, such as Megasphaera, Pectinatus, Selenomonas and Zymophilus, have a porous pseudo-outer-membrane that causes them to stain Gram-negative...
and Bacteroidetes
Bacteroidetes
The phylum Bacteroidetes is composed of three large classes of bacteria that are widely distributed in the environment, including in soil, in sediments, sea water and in the guts and on the skin of animals....
, especially in the digestion of fatty acids and dietary polysaccharides, as shown by experiments wherein the (caecum) gut flora of obese mice were transplanted into germ-free recipient mice, leading to an increase in weight despite a decrease in food consumption.
See also
- Helminthic therapyHelminthic therapyHelminthic therapy, a type of immunotherapy, is the treatment of autoimmune diseases and immune disorders by means of deliberate infestation with a helminth or with the ova of a helminth. Helminths are parasitic worms such as hookworms and whipworms....
- List of human flora
- Segmented filamentous bacteriaSegmented filamentous bacteriaSegmented filamentous bacteria are members of the gut flora that potently induce immune responses. Although not taxonomically classified, they have been given a candidate name "Candidatus Arthromitus"...
- Skin floraSkin floraThe skin flora are the microorganisms which reside on the skin. Most research has been upon those that reside upon the 2 square metres of human skin. Many of them are bacteria of which there are around 1000 species upon human skin from 19 phyla. The total number of bacteria on an average human has...
- ProbioticProbioticProbiotics are live microorganisms thought to be beneficial to the host organism. According to the currently adopted definition by FAO/WHO, probiotics are: "Live microorganisms which when administered in adequate amounts confer a health benefit on the host"...
Further reading
Books- Hattner, J.A.T./Anderes, S. ”Gut Insight: probiotics and prebiotics for digestive health and well-being”, 2009, Hattner Nutrition. ISBN 9780578026152
Review articles
- De Preter, V. et al. ”The impact of pre- and/or probiotics on human colonic metabolism: Does it affect human health?”, Molecular Nutrition & Food Research (2011),55(1):46-57.
- Prakash, S. et al. “Gut microbiota: next frontier in understanding human health and development of biotherapeutics”, Biologics: Targets & Therapy (2011), 5:71-86.