Gut microbiota

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"Enteric bacteria" redirects here. For other uses, see Enteric bacteria (disambiguation).

Escherichia coli, one of the many species of bacteria present in the human gut

Gut microbiota are the microorganisms, including bacteria and archaea, that live in

the digestive tracts of vertebrates including humans, and of insects.[1][2] Alternative terms
include gut flora (an outdated term that technically refers to plants)
and gut microbiome. The gastrointestinal metagenome (sometimes defined as
the microbiome) is the aggregate of all the genomes of gut microbiota.[3][4] In the human,
the gut is the main location of human microbiota.[5] The gut microbiota has broad
impacts, including effects on colonization, resistance to pathogens, maintaining
the intestinal epithelium, metabolizing dietary and pharmaceutical compounds,
controlling immune function, and even behavior through the gut-brain axis.
The microbial composition of the gut microbiota varies across regions of the digestive
tract. The colon contains the highest microbial density recorded in any habitat on Earth,
representing between 300 and 1000 different species.[6] However, 99% of gut bacteria
come from about 30 or 40 species.[7] Bacteria also make up to 60% of the dry mass
of feces.[8] Over 99% of the bacteria in the gut are anaerobes, but in the cecum, aerobic
bacteria reach high densities.[5] It is estimated that the human gut microbiota have
around a hundred times as many genes as there are in the human genome.

Contents

 1Overview
 2Classifications
o 2.1Enterotype
 3Composition
o 3.1Bacteriome
 3.1.1Stomach
  3.1.2Intestines
o 3.2Mycobiome
o 3.3Virome
 4Variation
o 4.1Age
o 4.2Diet
o 4.3Geography
 4.3.1Malnourishment
o 4.4Race and ethnicity
o 4.5Socioeconomic status
 5Acquisition in human infants
 6Functions
o 6.1Direct inhibition of pathogens
o 6.2Development of enteric protection and immune
system
o 6.3Metabolism
 6.3.1Pharmacomicrobiomics
o 6.4Gut-brain axis
 7Alterations in microbiota balance
o 7.1Effects of antibiotic use
o 7.2Pregnancy
o 7.3Probiotics, prebiotics, synbiotics, and
pharmabiotics
o 7.4Research
o 7.5Effects of exercise
 8Role in disease
o 8.1Ulcers
o 8.2Bowel perforation
o 8.3Inflammatory bowel diseases
o 8.4Irritable bowel syndrome
o 8.5Other inflammatory or autoimmune conditions
 8.5.1Asthma
 8.5.2Diabetes mellitus type 1
o 8.6Obesity and metabolic syndrome
o 8.7Liver disease
o 8.8Cancer
o 8.9Neuropsychiatric
 9Other animals
 10See also
 11Notes
 12References
 13Further reading

Overview[edit]
In humans, the gut microbiota has the largest numbers of bacteria and the greatest
number of species compared to other areas of the body. [9] In humans, the gut flora is
established at one to two years after birth, by which time the intestinal epithelium and
the intestinal mucosal barrier that it secretes have co-developed in a way that is tolerant
to, and even supportive of, the gut flora and that also provides a barrier to pathogenic
organisms.[10][11]
The relationship between some gut flora and humans is not merely commensal (a non-
harmful coexistence), but rather a mutualistic relationship.[5]: 700  Some human gut
microorganisms benefit the host by fermenting dietary fiber into short-chain fatty
acids (SCFAs), such as acetic acid and butyric acid, which are then absorbed by the
host.[9][12] Intestinal bacteria also play a role in synthesizing vitamin B and vitamin K as
well as metabolizing bile acids, sterols, and xenobiotics.[5][12] The systemic importance of
the SCFAs and other compounds they produce are like hormones and the gut flora itself
appears to function like an endocrine organ,[12] and dysregulation of the gut flora has
been correlated with a host of inflammatory and autoimmune conditions. [9][13]
The composition of human gut microbiota changes over time, when the diet changes,
and as overall health changes.[9][13] A systematic review from 2016 examined the
preclinical and small human trials that have been conducted with certain commercially
available strains of probiotic bacteria and identified those that had the most potential to
be useful for certain central nervous system disorders.[14]

Classifications[edit]
The microbial composition of the gut microbiota varies across the digestive tract. In
the stomach and small intestine, relatively few species of bacteria are generally present.
[6][15]
 The colon, in contrast, contains the highest microbial density recorded in any habitat
on Earth[16] with up to 1012 cells per gram of intestinal content.[6] These bacteria represent
between 300 and 1000 different species.[6][15] However, 99% of the bacteria come from
about 30 or 40 species.[7] As a consequence of their abundance in the intestine, bacteria
also make up to 60% of the dry mass of feces.[8] Fungi, protists, archaea,
and viruses are also present in the gut flora, but less is known about their activities. [17]
Over 99% of the bacteria in the gut are anaerobes, but in the cecum, aerobic
bacteria reach high densities.[5] It is estimated that these gut flora have around a
hundred times as many genes in total as there are in the human genome.[18]

Candida albicans, a dimorphic fungus that grows as a yeast in the gut

Many species in the gut have not been studied outside of their hosts because most
cannot be cultured.[15][7][19] While there are a small number of core species of microbes
shared by most individuals, populations of microbes can vary widely among different
individuals.[20] Within an individual, microbe populations stay fairly constant over time,
even though some alterations may occur with changes in lifestyle, diet and age. [6]
[21]
 The Human Microbiome Project has set out to better describe the microbiota of the
human gut and other body locations.
The four dominant bacterial phyla in the human gut
are Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria.[22] Most bacteria
belong to the genera Bacteroides, Clostridium, Faecalibacterium,[6]
[7]
 Eubacterium, Ruminococcus, Peptococcus, Peptostreptococcus, and Bifidobacterium.
[6][7]
 Other genera, such as Escherichia and Lactobacillus, are present to a lesser extent.
[6]
 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. [15]
Fungal genera that have been detected in the gut
include Candida, Saccharomyces, Aspergillus, Penicillium, Rhodotorula, Trametes, Ple
ospora, Sclerotinia, Bullera, and Galactomyces, among others.[23][24] Rhodotorula is most
frequently found in individuals with inflammatory bowel disease while Candida is most
frequently found in individuals with hepatitis B cirrhosis and chronic hepatitis B. [23]
Archaea constitute another large class of gut flora which are important in the
metabolism of the bacterial products of fermentation.
Industralization is associated with changes in the microbiota and the reduction of
diversity could drive certain species to extinction; in 2018, researchers proposed
a biobank repository of human microbiota.[25]
Enterotype[edit]
An enterotype is a classification of living organisms based on its
bacteriological ecosystem in the human gut microbiome not dictated by age, gender,
body weight, or national divisions.[26] There are indications that long-term diet influences
enterotype.[27] Three human enterotypes have been proposed,[26][28] but their value has
been questioned.[29]

Composition[edit]
See also: Human microbiome §  Gastrointestinal tract
Bacteriome[edit]
Stomach[edit]
Due to the high acidity of the stomach, most microorganisms cannot survive there. The
main bacterial inhabitants of the stomach
include: Streptococcus, Staphylococcus, Lactobacillus, Peptostreptococcus.[5]: 720  Helicob
acter pylori is a gram-negative spiral bacterium that establishes on gastric
mucosa causing chronic gastritis, and peptic ulcer disease, and is
a carcinogen for gastric cancer.[5]: 904 
Intestines[edit]

Bacteria commonly found in the human colon[30]

 Bacterium Incidence (%)

Bacteroides fragilis 100

Bacteroides melaninogenicus 100

Bacteroides oralis 100

Enterococcus faecalis 100

Escherichia coli 100

Enterobacter  sp. 40–80

Klebsiella sp. 40–80

Bifidobacterium bifidum 30–70

Staphylococcus aureus 30–50

Lactobacillus 20–60

Clostridium perfringens 25–35

Proteus mirabilis 5–55

Clostridium tetani 1–35

 Clostridium septicum 5–25

Pseudomonas aeruginosa 3–11

Salmonella enterica 3–7

Faecalibacterium prausnitzii ?common

Peptostreptococcus  sp. ?common

Peptococcus  sp. ?common

The small intestine contains a trace amount of microorganisms due to the proximity and
influence of the stomach. Gram-positive cocci and rod-shaped bacteria are the
predominant microorganisms found in the small intestine. [5] However, in the distal portion
of the small intestine alkaline conditions support gram-negative bacteria of
the Enterobacteriaceae.[5] The bacterial flora of the small intestine aid in a wide range of
intestinal functions. The bacterial flora provide regulatory signals that enable the
development and utility of the gut. Overgrowth of bacteria in the small intestine can lead
to intestinal failure.[31] In addition the large intestine contains the largest bacterial
ecosystem in the human body.[5] About 99% of the large intestine and feces flora are
made up of obligate anaerobes such as Bacteroides and Bifidobacterium.[32] Factors that
disrupt the microorganism population of the large intestine include antibiotics, stress,
and parasites.[5]
Bacteria make up most of the flora in the colon[33] and 60% of the dry mass of feces.
[6]
 This fact makes feces an ideal source of gut flora for any tests and experiments by
extracting the nucleic acid from fecal specimens, and bacterial 16S rRNA gene
sequences are generated with bacterial primers. This form of testing is also often
preferable to more invasive techniques, such as biopsies.
Five phyla dominate the intestinal
microbiota: bacteroidetes, firmicutes, actinobacteria, proteobacteria,
and verrucomicrobia—with bacteroidetes and firmicutes constituting 90% of the
composition.[34] Somewhere between 300[6] and 1000 different species live in the gut,
[15]
 with most estimates at about 500.[35][36] However, it is probable that 99% of the bacteria
come from about 30 or 40 species, with Faecalibacterium prausnitzii (phylum firmicutes)
being the most common species in healthy adults.[7][37]
Research suggests that the relationship between gut flora and humans is not
merely commensal (a non-harmful coexistence), but rather is
a mutualistic, symbiotic relationship.[15] Though people can survive with no gut flora,[35] the
microorganisms perform a host of useful functions, such as fermenting unused energy
substrates, training the immune system via end products of metabolism
like propionate and acetate, preventing growth of harmful species, 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. [5] Extensive modification and
imbalances of the gut microbiota and its microbiome or gene collection are associated
with obesity.[38] However, in certain conditions, some species are thought to be capable
of causing disease by causing infection or increasing cancer risk for the host.[6][33]
Mycobiome[edit]
Further information: Mycobiome
Fungi and protists also make up a part of the gut flora, but less is known about their
activities.[39]
Virome[edit]
Further information: Virome
The human virome is mostly bacteriophages.[40]

Variation[edit]
Age[edit]
It has been demonstrated that there are common patterns of microbiome composition
evolution during life.[41] In general, the diversity of microbiota composition of fecal
samples is significantly higher in adults than in children, although interpersonal
differences are higher in children than in adults. [42] Much of the maturation of microbiota
into an adult-like configuration happens during the three first years of life. [42]
As the microbiome composition changes, so does the composition of bacterial proteins
produced in the gut. In adult microbiomes, a high prevalence of enzymes involved in
fermentation, methanogenesis and the metabolism of arginine, glutamate, aspartate
and lysine have been found. In contrast, in infant microbiomes the dominant enzymes
are involved in cysteine metabolism and fermentation pathways. [42]
Diet[edit]
Studies and statistical analyses have identified the different bacterial genera in gut
microbiota and their associations with nutrient intake. Gut microflora is mainly
composed of three enterotypes: Prevotella, Bacteroides, and Ruminococcus. There is
an association between the concentration of each microbial community and diet. For
example, Prevotella is related to carbohydrates and simple sugars, while Bacteroides is
associated with proteins, amino acids, and saturated fats. Specialist microbes that
break down mucin survive on their host's carbohydrate excretions. [43] One enterotype will
dominate depending on the diet. Altering the diet will result in a corresponding change
in the numbers of species.[27] A 2021 study suggests that childhood diet and exercise can
substantially affect adult microbiome composition and diversity. The authors show that
mice on a high-fat diet as juveniles have lower bacterial diversity as adults after a
washout period equivalent to six human years. [44][45][46]
Geography[edit]
Gut microbiome composition depends on the geographic origin of populations.
Variations in a trade-off of Prevotella, the representation of the urease gene, and the
representation of genes encoding glutamate synthase/degradation or other enzymes
involved in amino acids degradation or vitamin biosynthesis show significant differences
between populations from the US, Malawi, or Amerindian origin.[42]
The US population has a high representation of enzymes encoding the degradation
of glutamine and enzymes involved in vitamin and lipoic acid biosynthesis; whereas
Malawi and Amerindian populations have a high representation of enzymes encoding
glutamate synthase and they also have an overrepresentation of α-amylase in their
microbiomes. As the US population has a diet richer in fats than Amerindian or
Malawian populations which have a corn-rich diet, the diet is probably the main
determinant of the gut bacterial composition.[42]
Further studies have indicated a large difference in the composition of microbiota
between European and rural African children. The fecal bacteria of children
from Florence were compared to that of children from the small rural village
of Boulpon in Burkina Faso. The diet of a typical child living in this village is largely
lacking in fats and animal proteins and rich in polysaccharides and plant proteins. The
fecal bacteria of European children were dominated by Firmicutes and showed a
marked reduction in biodiversity, while the fecal bacteria of the Boulpon children was
dominated by Bacteroidetes. The increased biodiversity and different composition of gut
flora in African populations may aid in the digestion of normally indigestible plant
polysaccharides and also may result in a reduced incidence of non-infectious colonic
diseases.[47]
On a smaller scale, it has been shown that sharing numerous common environmental
exposures in a family is a strong determinant of individual microbiome composition. This
effect has no genetic influence and it is consistently observed in culturally different
populations.[42]
Malnourishment[edit]
Malnourished children have less mature and less diverse gut microbiota than healthy
children, and changes in the microbiome associated with nutrient scarcity can in turn be
a pathophysiological cause of malnutrition.[48][49] Malnourished children also typically have
more potentially pathogenic gut flora, and more yeast in their mouths and throats.
[50]
 Altering diet may lead to changes in gut microbiota composition and diversity. [43]
Race and ethnicity[edit]
Researchers with the American Gut Project and Human Microbiome Project found that
twelve microbe families varied in abundance based on the race or ethnicity of the
individual. The strength of these associations is limited by the small sample size: the
American Gut Project collected data from 1,375 individuals, 90% of whom were white.
[51]
 The Healthy Life in an Urban Setting (HELIUS) study in Amsterdam found that those
of Dutch ancestry had the highest level of gut microbiota diversity, while those of South
Asian and Surinamese descent had the lowest diversity. The study results suggested
that individuals of the same race or ethnicity have more similar microbiomes than
individuals of different racial backgrounds.[51]
Socioeconomic status[edit]
As of 2020, at least two studies have demonstrated a link between an
individual's socioeconomic status (SES) and their gut microbiota. A study
in Chicago found that individuals in higher SES neighborhoods had greater microbiota
diversity. People from higher SES neighborhoods also had more
abundant Bacteroides bacteria. Similarly, a study of twins in the United Kingdom found
that higher SES was also linked with a greater gut diversity. [51]

Acquisition in human infants[edit]

The establishment of a gut flora is crucial to the health of an adult, as well as the
functioning of the gastrointestinal tract. [52] In humans, a gut flora similar to an adult's is
formed within one to two years of birth as microbiota are acquired through parent-to-
child transmission and transfer from food, water, and other environmental sources. [53][10]
The traditional view of the gastrointestinal tract of a normal fetus is that it is sterile,
although this view has been challenged in the past few years. [54] Multiple lines of
evidence have begun to emerge that suggest there may be bacteria in the intrauterine
environment. In humans, research has shown that microbial colonization may occur in
the fetus[55] with one study showing Lactobacillus and Bifidobacterium species were
present in placental biopsies.[56] Several rodent studies have demonstrated the presence
of bacteria in the amniotic fluid and placenta, as well as in the meconium of babies born
by sterile cesarean section.[57][58] In another study, researchers administered a culture of
bacteria orally to a pregnant dam, and detected the bacteria in the offspring, likely
resulting from transmission between the digestive tract and amniotic fluid via the blood
stream.[59] However, researchers caution that the source of these intrauterine bacteria,
whether they are alive, and their role, is not yet understood. [60][56]
During birth and rapidly thereafter, bacteria from the mother and the surrounding
environment colonize the infant's gut. [10] The exact sources of bacteria is not fully
understood, but may include the birth canal, other people (parents, siblings, hospital
workers), breastmilk, food, and the general environment with which the infant interacts.
[61]
 However, as of 2013, it remains unclear whether most colonizing arises from the
mother or not.[10] Infants born by caesarean section 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.[55] During the first year of life, the composition of the gut flora is generally
simple and changes a great deal with time and is not the same across individuals. [10] The
initial bacterial population are generally facultative anaerobic organisms; investigators
believe that these initial colonizers decrease the oxygen concentration in the gut, which
in turn allows obligately anaerobic bacteria like Bacteroides, Actinobacteria,
and Firmicutes to become established and thrive.[10] Breast-fed babies become
dominated by bifidobacteria, possibly due to the contents of bifidobacterial growth
factors in breast milk, and by the fact that breast milk carries prebiotic components,
allowing for healthy bacterial growth. [56][62] In contrast, the microbiota of formula-
fed infants is more diverse, with high numbers
of Enterobacteriaceae, enterococci, bifidobacteria, Bacteroides, and clostridia.[63]
Caesarean section, antibiotics, and formula feeding may alter the gut microbiome
composition.[56] Children treated with antibiotics have less stable, and less diverse floral
communities.[64] Caesarean sections have been shown to be disruptive to mother-
offspring transmission of bacteria, which impacts the overall health of the offspring by
raising risks of disease such as celiacs, asthma, and type 1 diabetes. [56] This further
evidences the importance of a healthy gut microbiome. Various methods of microbiome
restoration are being explored, typically involving exposing the infant to maternal vaginal
contents, and oral probiotics.[56]

Functions[edit]
When the study of gut flora began in 1995,[65] it was thought to have three key roles:
direct defense against pathogens, fortification of host defense by its role in developing
and maintaining the intestinal epithelium and inducing antibody production there, and
metabolizing otherwise indigestible compounds in food; subsequent work discovered its
role in training the developing immune system, and yet further work focused on its role
in the gut-brain axis.[66]
Direct inhibition of pathogens[edit]
The gut flora community plays a direct role in defending against pathogens by fully
colonising the space, making use of all available nutrients, and by secreting compounds
that kill or inhibit unwelcome organisms that would compete for nutrients with it, these
compounds are known as cytokines.[67] Different strains of gut bacteria cause the
production of different cytokines. Cytokines are chemical compounds produced by our
immune system for initiating the inflammatory response against infections. Disruption of
the gut flora allows competing organisms like Clostridium difficile to become established
that otherwise are kept in abeyance.[67]
Development of enteric protection and immune system[edit]

Microfold cells transfer antigens (Ag) from the lumen of the gut to gut-associated lymphoid tissue (GALT)
via transcytosis and present them to different innate and adaptive immune cells.
In humans, a gut flora similar to an adult's is formed within one to two years of birth.
[10]
 As the gut flora gets established, the lining of the intestines – the intestinal epithelium
and the intestinal mucosal barrier that it secretes – develop as well, in a way that is
tolerant to, and even supportive of, commensalistic microorganisms to a certain extent
and also provides a barrier to pathogenic ones.[10] Specifically, goblet cells that produce
the mucosa proliferate, and the mucosa layer thickens, providing an outside mucosal
layer in which "friendly" microorganisms can anchor and feed, and an inner layer that
even these organisms cannot penetrate. [10][11] Additionally, the development of gut-
associated lymphoid tissue (GALT), which forms part of the intestinal epithelium and
which detects and reacts to pathogens, appears and develops during the time that the
gut flora develops and established.[10] The GALT that develops is tolerant to gut flora
species, but not to other microorganisms.[10] GALT also normally becomes tolerant to
food to which the infant is exposed, as well as digestive products of food, and gut
flora's metabolites (molecules formed from metabolism) produced from food. [10]
The human immune system creates cytokines that can drive the immune system to
produce inflammation in order to protect itself, and that can tamp down the immune
response to maintain homeostasis and allow healing after insult or injury.[10] Different
bacterial species that appear in gut flora have been shown to be able to drive the
immune system to create cytokines selectively; for example Bacteroides fragilis and
some Clostridia species appear to drive an anti-inflammatory response, while
some segmented filamentous bacteria drive the production of inflammatory cytokines.[10]
[68]
 Gut flora can also regulate the production of antibodies by the immune system.[10]
[69]
 One function of this regulation is to cause B cells to class switch to IgA. In most cases
B cells need activation from T helper cells to induce class switching; however, in
another pathway, gut flora cause NF-kB signaling by intestinal epithelial cells which
results in further signaling molecules being secreted. [70] These signaling molecules
interact with B cells to induce class switching to IgA. [70] IgA is an important type of
antibody that is used in mucosal environments like the gut. It has been shown that IgA
can help diversify the gut community and helps in getting rid of bacteria that cause
inflammatory responses.[71] Ultimately, IgA maintains a healthy environment between the
host and gut bacteria.[71] These cytokines and antibodies can have effects outside the
gut, in the lungs and other tissues.[10]
The immune system can also be altered due to the gut bacteria's ability to
produce metabolites that can affect cells in the immune system. For example short-
chain fatty acids (SCFA) can be produced by some gut bacteria through fermentation.
[72]
 SCFAs stimulate a rapid increase in the production of innate immune cells
like neutrophils, basophils and eosinophils.[72] These cells are part of the innate immune
system that try to limit the spread of infection.
Metabolism[edit]
Tryptophan metabolism by human gastrointestinal microbiota (
 v
 t
 e
)
Tryptophan
Clostridium
sporogenes
Lacto-
bacilli
Tryptophanase-
expressing
bacteria
IPA
I3A
Indole
Liver
Brain
IPA
I3A
Indole
Indoxyl
sulfate
AST-120
AhR
Intestinal
immune
cells
Intestinal
epithelium
PXR
Mucosal homeostasis:
↓TNF-α
↑Junction protein-
coding mRNAs
L cell
GLP-1
TJ
Neuroprotectant:
↓Activation of glial cells and astrocytes
↓4-Hydroxy-2-nonenal levels
↓DNA damage
–Antioxidant
–Inhibits β-amyloid fibril formation
Maintains mucosal reactivity:
↑IL-22 production
Associated with vascular disease:
↑Oxidative stress
↑Smooth muscle cell proliferation
↑Aortic wall thickness and calcification
Associated with chronic kidney disease:
↑Renal dysfunction
–Uremic toxin
Kidneys

This diagram shows the biosynthesis of bioactive compounds (indole and certain other derivatives) from tryptophan by
bacteria in the gut.[73] Indole is produced from tryptophan by bacteria that express tryptophanase.[73] Clostridium
sporogenes metabolizes tryptophan into indole and subsequently 3-indolepropionic acid (IPA),[74] a highly
potent neuroprotective antioxidant that scavenges hydroxyl radicals.[73][75][76] IPA binds to the pregnane X receptor (PXR) in
intestinal cells, thereby facilitating mucosal homeostasis and barrier function.[73] Following absorption from the intestine
and distribution to the brain, IPA confers a neuroprotective effect against cerebral ischemia and Alzheimer's disease.
[73]
 Lactobacillus species metabolize tryptophan into indole-3-aldehyde (I3A) which acts on the aryl hydrocarbon
receptor (AhR) in intestinal immune cells, in turn increasing interleukin-22 (IL-22) production.[73] Indole itself triggers the
secretion of glucagon-like peptide-1 (GLP-1) in intestinal L cells and acts as a ligand for AhR.[73] Indole can also be
metabolized by the liver into indoxyl sulfate, a compound that is toxic in high concentrations and associated with vascular
disease and renal dysfunction.[73] AST-120 (activated charcoal), an intestinal sorbent that is taken by mouth, adsorbs indole,
in turn decreasing the concentration of indoxyl sulfate in blood plasma. [73]

Without gut flora, the human body would be unable to utilize some of the
undigested carbohydrates it consumes, because some types of gut flora
have enzymes that human cells lack for breaking down certain polysaccharides.
[12]
 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.
[12]
 Carbohydrates that humans cannot digest without bacterial help include
certain starches, fiber, oligosaccharides, and sugars that the body failed to digest and
absorb like lactose in the case of lactose intolerance and sugar
alcohols, mucus produced by the gut, and proteins.[9][12]
Bacteria turn carbohydrates they ferment into short-chain fatty acids by a form of
fermentation called saccharolytic fermentation.[36] Products include acetic acid, propionic
acid and butyric acid.[7][36] These materials can be used by host cells, providing a major
source of energy and nutrients.[36] Gases (which are involved in signaling[77] and may
cause flatulence) and organic acids, such as lactic acid, are also produced by
fermentation.[7] Acetic acid is used by muscle, propionic acid facilitates liver production
of ATP, and butyric acid provides energy to gut cells.[36]
Gut flora also synthesize vitamins like biotin and folate, and facilitate absorption
of dietary minerals, including magnesium, calcium, and iron.[6][21] Methanobrevibacter
smithii is unique because it is not a species of bacteria, but rather a member
of domain Archaea, and is the most abundant methane-producing archaeal species in
the human gastrointestinal microbiota.[78]
Gut microbiota also serve as a source of Vitamins K and B12 that are not produced by
the body or produced in little amount. [79][80]
Pharmacomicrobiomics[edit]
The human metagenome (i.e., the genetic composition of an individual and all
microorganisms that reside on or within the individual's body) varies considerably
between individuals.[81][82] Since the total number of microbial and viral cells in the human
body (over 100 trillion) greatly outnumbers Homo sapiens cells (tens of trillions),[note 1][81]
[83]
 there is considerable potential for interactions between drugs and an individual's
microbiome, including: drugs altering the composition of the human microbiome, drug
metabolism by microbial enzymes modifying the drug's pharmacokinetic profile, and
microbial drug metabolism affecting a drug's clinical efficacy and toxicity profile.[81][82][84]
Apart from carbohydrates, gut microbiota can also metabolize other xenobiotics such as
drugs, phytochemicals, and food toxicants. More than 30 drugs have been shown to be
metabolized by gut microbiota.[85] The microbial metabolism of drugs can sometimes
inactivate the drug.[86]
Gut-brain axis[edit]
Main article: Gut-brain axis
The gut-brain axis is the biochemical signaling that takes place between
the gastrointestinal tract and the central nervous system.[66] That term has been
expanded to include the role of the gut flora in the interplay; the term "microbiome-gut-
brain axis" is sometimes used to describe paradigms explicitly including the gut flora. [66][87]
[88]
 Broadly defined, the gut-brain axis includes the central nervous
system, neuroendocrine and neuroimmune systems including the hypothalamic–
pituitary–adrenal axis (HPA axis), sympathetic and parasympathetic arms of
the autonomic nervous system including the enteric nervous system, the vagus nerve,
and the gut microbiota.[66][88]
A systematic review from 2016 examined the preclinical and small human trials that
have been conducted with certain commercially available strains of probiotic bacteria
and found that among those tested, Bifidobacterium and Lactobacillus genera (B.
longum, B. breve, B. infantis, L. helveticus, L. rhamnosus, L. plantarum, and L. casei),
had the most potential to be useful for certain central nervous system disorders.[14]

Alterations in microbiota balance[edit]

Effects of antibiotic use[edit]
Altering the numbers of gut bacteria, for example by taking broad-spectrum antibiotics,
may affect the host's health and ability to digest food. [89] Antibiotics can cause antibiotic-
associated diarrhea by irritating the bowel directly, changing the levels of microbiota, or
allowing pathogenic bacteria to grow.[7] 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. [89]
Changing the numbers and species of gut microbiota 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 microbiota could cause diarrhea. [7]
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.[6][7][89] Emerging treatment protocols for C. difficile infections involve
fecal microbiota transplantation of donor feces (see Fecal transplant).[90] Initial reports of
treatment describe success rates of 90%, with few side effects. Efficacy is speculated to
result from restoring bacterial balances of bacteroides and firmicutes classes of
bacteria.[91]
The composition of the gut microbiome 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, a treatment to kill only pathogenic bacteria and allow the re-
establishment of healthy ones.[92]
Antibiotics alter the population of the microbiota in the gastrointestinal tract, and this
may change the intra-community metabolic interactions, modify caloric intake by using
carbohydrates, and globally affects host metabolic, hormonal and immune homeostasis.
[93]

There is reasonable evidence that taking probiotics containing Lactobacillus species

may help prevent antibiotic-associated diarrhea and that taking probiotics
with Saccharomyces (e.g., Saccharomyces boulardii  ) may help to prevent Clostridium
difficile infection following systemic antibiotic treatment. [94]
Pregnancy[edit]
The gut microbiota of a woman changes as pregnancy advances, with the changes
similar to those seen in metabolic syndromes such as diabetes. The change in gut
microbiota causes no ill effects. The newborn's gut microbiota resemble the mother's
first-trimester samples. The diversity of the microbiome decreases from the first to third
trimester, as the numbers of certain species go up.[56][95]
Probiotics, prebiotics, synbiotics, and pharmabiotics[edit]
Probiotics are microorganisms that are believed to provide health benefits when
consumed.[96][97] With regard to gut microbiota, prebiotics are typically non-
digestible, fiber compounds that pass undigested through the upper part of
the gastrointestinal tract and stimulate the growth or activity of advantageous gut flora
by acting as substrate for them.[36][98]
Synbiotics refers to food ingredients or dietary supplements combining probiotics and
prebiotics in a form of synergism.[99]
The term "pharmabiotics" is used in various ways, to mean: pharmaceutical
formulations (standardized manufacturing that can obtain regulatory approval as a drug)
of probiotics, prebiotics, or synbiotics;[100] probiotics that have been genetically
engineered or otherwise optimized for best performance (shelf life, survival in the
digestive tract, etc.);[101] and the natural products of gut flora metabolism (vitamins, etc.).
[102]

There is some evidence that treatment with some probiotic strains of bacteria may be
effective in irritable bowel syndrome and chronic idiopathic constipation. Those
organisms most likely to result in a decrease of symptoms have included:

 Enterococcus faecium
 Lactobacillus plantarum
 Lactobacillus rhamnosus
 Propionibacterium freudenreichii
 Bifidobacterium breve
 Lactobacillus reuteri
 Lactobacillus salivarius
 Bifidobacterium infantis
 Streptococcus thermophilus[103][104][105]
Research[edit]
Tests for whether non-antibiotic drugs may impact human gut-associated bacteria were
performed by in vitro analysis on more than 1000 marketed drugs against 40 gut
bacterial strains, demonstrating that 24% of the drugs inhibited the growth of at least
one of the bacterial strains.[106]
Effects of exercise[edit]
Gut microbiota and exercise have recently been shown to be interconnected. Both
moderate and intense exercise are typically part of the training regimen of endurance
athletes, but they exert different effects on health. The interconnection between gut
microbiota and endurance sports depends upon exercise intensity and training status. [107]

Role in disease[edit]
Bacteria in the digestive tract can contribute to and be affected by disease in various
ways. The presence or overabundance of some kinds of bacteria may contribute to
inflammatory disorders such as inflammatory bowel disease.[6] Additionally, metabolites
from certain members of the gut flora may influence host signalling pathways,
contributing to disorders such as obesity and colon cancer.[6] Alternatively, in the event
of a breakdown of the gut epithelium, the intrusion of gut flora components into other
host compartments can lead to sepsis.[6]
Ulcers[edit]
Helicobacter pylori infection can initiate formation of stomach ulcers when the bacteria
penetrate the stomach epithelial lining, then causing an inflammatory phagocytotic
response.[108] In turn, the inflammation damages parietal cells which release excessive
hydrochloric acid into the stomach and produce less of the protective mucus. [109] Injury to
the stomach lining, leading to ulcers, develops when gastric acid overwhelms the
defensive properties of cells and inhibits endogenous prostaglandin synthesis, reduces
mucus and bicarbonate secretion, reduces mucosal blood flow, and lowers resistance to
injury.[109] Reduced protective properties of the stomach lining increase vulnerability to
further injury and ulcer formation by stomach acid, pepsin, and bile salts. [108][109]
Bowel perforation[edit]
Normally-commensal bacteria can harm the host if they extrude from the intestinal tract.
[10][11]
 Translocation, which occurs when bacteria leave the gut through its mucosal lining,
can occur in a number of different diseases. [11] If the gut is perforated, bacteria invade
the interstitium, causing a potentially fatal infection.[5]: 715 
Inflammatory bowel diseases[edit]
The two main types of inflammatory bowel diseases, Crohn's disease and ulcerative
colitis, are chronic inflammatory disorders of the gut; the causes of these diseases are
unknown and issues with the gut flora and its relationship with the host have been
implicated in these conditions.[13][110][111][112] Additionally, it appears that interactions of gut
flora with the gut-brain axis have a role in IBD, with physiological stress mediated
through the hypothalamic–pituitary–adrenal axis driving changes to intestinal epithelium
and the gut flora in turn releasing factors and metabolites that trigger signaling in
the enteric nervous system and the vagus nerve.[4]
The diversity of gut flora appears to be significantly diminished in people with
inflammatory bowel diseases compared to healthy people; additionally, in people with
ulcerative colitis, Proteobacteria and Actinobacteria appear to dominate; in people with
Crohn's, Enterococcus faecium and several Proteobacteria appear to be over-
represented.[4]
There is reasonable evidence that correcting gut flora imbalances by taking probiotics
with Lactobacilli and Bifidobacteria can reduce visceral pain and gut inflammation in
IBD.[94]
Irritable bowel syndrome[edit]
Irritable bowel syndrome is a result of stress and chronic activation of the HPA axis; its
symptoms include abdominal pain, changes in bowel movements, and an increase in
proinflammatory cytokines. Overall, studies have found that the luminal and mucosal
microbiota are changed in irritable bowel syndrome individuals, and these changes can
relate to the type of irritation such as diarrhea or constipation. Also, there is a decrease
in the diversity of the microbiome with low levels of fecal Lactobacilli and Bifidobacteria,
high levels of facultative anaerobic bacteria such as Escherichia coli, and increased
ratios of Firmicutes: Bacteroidetes.[88]
Other inflammatory or autoimmune conditions[edit]
Allergy, asthma, and diabetes mellitus are autoimmune and inflammatory disorders of
unknown cause, but have been linked to imbalances in the gut flora and its relationship
with the host.[13] As of 2016 it was not clear if changes to the gut flora cause these auto-
immune and inflammatory disorders or are a product of or adaptation to them. [13][113]
Asthma[edit]
With asthma, two hypotheses have been posed to explain its rising prevalence in the
developed world. The hygiene hypothesis posits that children in the developed world
are not exposed to enough microbes and thus may contain lower prevalence of specific
bacterial taxa that play protective roles. [114] The second hypothesis focuses on
the Western pattern diet, which lacks whole grains and fiber and has an overabundance
of simple sugars.[13] Both hypotheses converge on the role of short-chain fatty acids
(SCFAs) in immunomodulation. These bacterial fermentation metabolites are involved in
immune signalling that prevents the triggering of asthma and lower SCFA levels are
associated with the disease.[114][115] Lacking protective genera such
as Lachnospira, Veillonella, Rothia and Faecalibacterium has been linked to reduced
SCFA levels.[114] Further, SCFAs are the product of bacterial fermentation of fiber, which
is low in the Western pattern diet.[13][115] SCFAs offer a link between gut flora and immune
disorders, and as of 2016, this was an active area of research. [13] Similar hypotheses
have also been posited for the rise of food and other allergies. [116]
Diabetes mellitus type 1[edit]
The connection between the gut microbiota and diabetes mellitus type 1 has also been
linked to SCFAs, such as butyrate and acetate. Diets yielding butyrate and acetate from
bacterial fermentation show increased Treg expression.[117] Treg cells downregulate effector
T cells, which in turn reduces the inflammatory response in the gut.[118] Butyrate is an
energy source for colon cells. butyrate-yielding diets thus decrease gut permeability by
providing sufficient energy for the formation of tight junctions.[119] Additionally, butyrate
has also been shown to decrease insulin resistance, suggesting gut communities low in
butyrate-producing microbes may increase chances of acquiring diabetes mellitus type
2.[120] Butyrate-yielding diets may also have potential colorectal cancer suppression
effects.[119]
Obesity and metabolic syndrome[edit]
The gut flora has also been implicated in obesity and metabolic syndrome due to the
key role it plays in the digestive process; the Western pattern diet appears to drive and
maintain changes in the gut flora that in turn change how much energy is derived from
food and how that energy is used.[112][121] One aspect of a healthy diet that is often lacking
in the Western-pattern diet is fiber and other complex carbohydrates that a healthy gut
flora require flourishing; changes to gut flora in response to a Western-pattern diet
appear to increase the amount of energy generated by the gut flora which may
contribute to obesity and metabolic syndrome. [94] There is also evidence that microbiota
influence eating behaviours based on the preferences of the microbiota, which can lead
to the host consuming more food eventually resulting in obesity. It has generally been
observed that with higher gut microbiome diversity, the microbiota will spend energy
and resources on competing with other microbiota and less on manipulating the host.
The opposite is seen with lower gut microbiome diversity, and these microbiotas may
work together to create host food cravings.[43]
Additionally, the liver plays a dominant role in blood glucose homeostasis by
maintaining a balance between the uptake and storage of glucose through the
metabolic pathways of glycogenesis and gluconeogenesis. Intestinal lipids regulate
glucose homeostasis involving a gut-brain-liver axis. The direct administration of lipids
into the upper intestine increases the long chain fatty acyl-coenzyme A (LCFA-CoA)
levels in the upper intestines and suppresses glucose production even under
subdiaphragmatic vagotomy or gut vagal deafferentation. This interrupts the neural
connection between the brain and the gut and blocks the upper intestinal lipids' ability to
inhibit glucose production. The gut-brain-liver axis and gut microbiota composition can
regulate the glucose homeostasis in the liver and provide potential therapeutic methods
to treat obesity and diabetes.[122]
Just as gut flora can function in a feedback loop that can drive the development of
obesity, there is evidence that restricting intake of calories (i.e., dieting) can drive
changes to the composition of the gut flora.[112]
Liver disease[edit]
As the liver is fed directly by the portal vein, whatever crosses the intestinal epithelium
and the intestinal mucosal barrier enters the liver, as do cytokines generated there.
[123]
 Dysbiosis in the gut flora has been linked with the development of cirrhosis and non-
alcoholic fatty liver disease.[123]
Cancer[edit]
Some genera of bacteria, such as Bacteroides and Clostridium, have been associated
with an increase in tumor growth rate, while other genera, such
as Lactobacillus and Bifidobacteria, are known to prevent tumor formation.[6] As of
December 2017 there was preliminary and indirect evidence that gut microbiota might
mediate response to PD-1 inhibitors; the mechanism was unknown.[124]
Neuropsychiatric[edit]
Main article: Gut-brain axis
Interest in the relationship between gut flora and neuropsychiatric issues was sparked
by a 2014 study showing that germ-free mice showed an exaggerated HPA axis
response to stress compared to non-GF laboratory mice. [66] As of January 2016, most of
the work that has been done on the role of gut flora in the gut-brain axis had been
conducted in animals, or characterizing the various neuroactive compounds that gut
flora can produce, and studies with humans measuring differences between people with
various psychiatric and neurological differences, or changes to gut flora in response to
stress, or measuring effects of various probiotics (dubbed "psychobiotics in this
context), had generally been small and could not be generalized; whether changes to
gut flora are a result of disease, a cause of disease, or both in any number of possible
feedback loops in the gut-brain axis, remained unclear. [66][94]
A systematic review from 2016 examined the preclinical and small human trials that
have been conducted with certain commercially available strains of probiotic bacteria
and found that among those tested, the genera Bifidobacterium and Lactobacillus (B.
longum, B. breve, B. infantis, L. helveticus, L. rhamnosus, L. plantarum, and L. casei)
had the most potential to be useful for certain central nervous system disorders. [14]

Other animals[edit]
The composition of the human gut microbiome is similar to that of the other great apes.
However, humans’ gut biota has decreased in diversity and changed in composition
since our evolutionary split from Pan.[125] Humans display increases in Bacteroidetes, a
bacterial phylum associated with diets high in animal protein and fat, and decreases in
Methanobrevibacter and Fibrobacter, groups that ferment complex plant
polysaccharides.[125] These changes are the result of the combined dietary, genetic, and
cultural changes humans have undergone since evolutionary divergence from Pan.
In addition to humans and vertebrates, some insects also possess complex and diverse
gut microbiota that play key nutritional roles. [2] Microbial communities associated with
termites can constitute a majority of the weight of the individuals and perform important
roles in the digestion of lignocellulose and nitrogen fixation.[126] These communities are
host-specific, and closely related insect species share comparable similarities in gut
microbiota composition.[127][128] In cockroaches, gut microbiota have been shown to
assemble in a deterministic fashion, irrespective of the inoculum;[129] the reason for this
host-specific assembly remains unclear. Bacterial communities associated with insects
like termites and cockroaches are determined by a combination of forces, primarily diet,
but there is some indication that host phylogeny may also be playing a role in the
selection of lineages.[127][128]
For more than 51 years it has been known that the administration of low doses of
antibacterial agents promotes the growth of farm animals to increase weight gain. [93]
In a study carried out on mice the ratio of Firmicutes and Lachnospiraceae was
significantly elevated in animals treated with subtherapeutic doses of different
antibiotics. By analyzing the caloric content of faeces and the concentration of small
chain fatty acids (SCFAs) in the GI tract, it was concluded that the changes in the
composition of microbiota lead to an increased capacity to extract calories from
otherwise indigestible constituents, and to an increased production of SCFAs. These
findings provide evidence that antibiotics perturb not only the composition of the GI
microbiome but also its metabolic capabilities, specifically with respect to SCFAs. [93]

See also[edit]

 Biology portal

 Medicine portal

 Colonisation resistance
 List of human flora
  List of microbiota species of the lower reproductive
tract of women
 Skin flora
 Verotoxin-producing Escherichia coli

Notes[edit]
1. ^ There is substantial variation in microbiome composition
and microbial concentrations by anatomical site. [81][82] Fluid
from the human colon – which contains the highest
concentration of microbes of any anatomical site – contains
approximately one trillion (10^12) bacterial cells/ml. [81]

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54. ^ Perez-Muñoz, Maria Elisa; Arrieta, Marie-Claire; Ramer-
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55. ^ Jump up to:a b Matamoros, Sebastien; Gras-Leguen,
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57. ^ Jiménez, Esther; Fernández, Leonides; Marín, María L;
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58. ^ Collado, Maria Carmen; Rautava, Samuli; Aakko, Juhani;
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59. ^ Jiménez, Esther; Marín, María L.; Martín, Rocío; Odriozola,
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60. ^ Perez-Muñoz, Maria Elisa; Arrieta, Marie-Claire; Ramer-
Tait, Amanda E; Walter, Jens (2017).  "A critical assessment
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Implications for research on the pioneer infant
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IPA also potently scavenges hydroxyl radicals
Table 2: Microbial metabolites: their synthesis, mechanisms of
action, and effects on health and disease
Figure 1: Molecular mechanisms of action of indole and its
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IPA metabolism diagram
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ID  6630247.  [Indole-3-propionic acid (IPA)] has previously
been identified in the plasma and cerebrospinal fluid of
humans, but its functions are not known. ... In kinetic
competition experiments using free radical-trapping agents,
the capacity of IPA to scavenge hydroxyl radicals exceeded
that of melatonin, an indoleamine considered to be the most
potent naturally occurring scavenger of free radicals. In
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77. ^ Hopper, Christopher P.; De La Cruz, Ladie Kimberly; Lyles,
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414.  doi:10.1089/omi.2014.0018.  PMC 4086029. PMID 2478
5449.  The hundred trillion microbes and viruses residing in
every human body, which outnumber human cells and
contribute at least 100 times more genes than those encoded
on the human genome (Ley et al., 2006), offer an immense
accessory pool for inter-individual genetic variation that has
been underestimated and largely unexplored (Savage, 1977;
Medini et al., 2008; Minot et al., 2011; Wylie et al., 2012).  ...
Meanwhile, a wealth of literature has long been available
about the biotransformation of xenobiotics, notably by gut
bacteria (reviewed in Sousa et al., 2008; Rizkallah et al.,
2010; Johnson et al., 2012; Haiser and Turnbaugh, 2013).
This valuable information is predominantly about drug
metabolism by unknown human-associated microbes;
however, only a few cases of inter-individual microbiome
variations have been documented [e.g., digoxin (Mathan et
al., 1989) and acetaminophen (Clayton et al., 2009)].
82. ^ Jump up to:a b c Cho I, Blaser MJ (March 2012). "The human
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The composition of the microbiome varies by anatomical site
(Figure 1). The primary determinant of community
composition is anatomical location: interpersonal variation is
substantial23,24  and is higher than the temporal variability seen
at most sites in a single individual25.  ... How does the
microbiome affect the pharmacology of medications? Can we
“micro-type” people to improve pharmacokinetics and/or
reduce toxicity? Can we manipulate the microbiome to
improve pharmacokinetic stability?
83. ^ Hutter T, Gimbert C, Bouchard F, Lapointe FJ
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9. doi:10.1186/s40168-015-0076-7.  PMC 4359430. PMID 25
774294. Some metagenomic studies have suggested that
less than 10% of the cells that comprise our bodies are Homo
sapiens cells. The remaining 90% are bacterial cells. The
description of this so-called human microbiome is of great
interest and importance for several reasons. For one, it helps
us redefine what a biological individual is. We suggest that a
human individual is now best described as a super-individual
 in which a large number of different species (including Homo
sapiens) coexist.
84. ^ Kumar K, Dhoke GV, Sharma AK, Jaiswal SK, Sharma VK
(January 2019). "Mechanistic elucidation of amphetamine
metabolism by tyramine oxidase from human gut microbiota
using molecular dynamics simulations".  Journal of Cellular
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13138. Particularly in the case of the human gut, which
harbors a large diversity of bacterial species, the differences
in microbial composition can significantly alter the metabolic
activity in the gut lumen.4 The differential metabolic activity
due to the differences in gut microbial species has been
recently linked with various metabolic disorders and
diseases.5-12 In addition to the impact of gut microbial diversity
or dysbiosis in various human diseases, there is an
increasing amount of evidence which shows that the gut
microbes can affect the bioavailability and efficacy of various
orally administrated drug molecules through promiscuous
enzymatic metabolism.13,14 ... The present study on the
atomistic details of amphetamine binding and binding affinity
to the tyramine oxidase along with the comparison with two
natural substrates of this enzyme namely tyramine and
phenylalanine provides strong evidence for the promiscuity ‐
based metabolism of amphetamine by the tyramine oxidase
enzyme of E. coli. The obtained results will be crucial in
designing a surrogate molecule for amphetamine that can
help either in improving the efficacy and bioavailability of the
amphetamine drug via competitive inhibition or in redesigning
the drug for better pharmacological effects. This study will
also have useful clinical implications in reducing the gut
microbiota caused variation in the drug response among
different populations.
85. ^ Sousa, Tiago; Paterson, Ronnie; Moore, Vanessa;
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Further reading[edit]
Review articles

 Maranduba, Carlos Magno da Costa; De Castro,

Sandra Bertelli Ribeiro; Souza, Gustavo Torres de;
Rossato, Cristiano; Da Guia, Francisco Carlos;
Valente, Maria Anete Santana; Rettore, João Vitor
Paes; Maranduba, Claudinéia Pereira; Souza,
Camila Maurmann de; Carmo, Antônio Márcio
Resende do; MacEdo, Gilson Costa; Silva,
Fernando de Sá (2015). "Intestinal Microbiota as
Modulators of the Immune System and
Neuroimmune System: Impact on the Host Health
and Homeostasis". Journal of Immunology
Research. 2015:
931574. doi:10.1155/2015/931574. PMC 4352473. 
PMID 25759850.
 De Preter, Vicky; Hamer, Henrike M; Windey, Karen;
Verbeke, Kristin (2011). "The impact of pre- and/or
probiotics on human colonic metabolism: Does it
affect human health?". Molecular Nutrition & Food
Research. 55 (1): 46–
57. doi:10.1002/mnfr.201000451. PMID 21207512.
 Prakash, Satya; Rodes, Laetitia; Coussa-Charley,
Michael; Tomaro-Duchesneau, Catherine; Tomaro-
Duchesneau, Catherine; Coussa-Charley; Rodes
(2011). "Gut microbiota: Next frontier in
understanding human health and development of
biotherapeutics". Biologics: Targets and Therapy. 5:
71–86. doi:10.2147/BTT.S19099. PMC 3156250. P
MID 21847343.
 Wu, G. D.; Chen, J.; Hoffmann, C.; Bittinger, K.;
Chen, Y.-Y.; Keilbaugh, S. A.; Bewtra, M.; Knights,
D.; Walters, W. A.; Knight, R.; Sinha, R.; Gilroy, E.;
Gupta, K.; Baldassano, R.; Nessel, L.; Li, H.;
 Bushman, F. D.; Lewis, J.D. (2011). "Linking Long-
Term Dietary Patterns with Gut Microbial
Enterotypes". Science. 334 (6052): 105–
08. Bibcode:2011Sci...334..105W. doi:10.1126/scie
nce.1208344. PMC 3368382. PMID 21885731.
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Human microbiota

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o In pregnancy
man flora
o In bacterial vaginosis

 Placenta

 Uterus

 Salivary

 Human virome

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ders and  Dysbiosis

herapies  Faecal transfer

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