Gut microbiota
Introduction
Gut microbiota are the microorganisms that are found living in the digestive tracts of humans. Alternative terms
include gut flora and gut microbiome. The gastro intestinal metagenome is the aggregate of all the genomes of gut microbiota. In the human, the gut is the main location of human microbiota.
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
relationship between some gut flora and humans is not merely commensal, a non-harmful coexistence but
rather a mutualistic relationship. 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. Intestinal bacteria also play a role in
synthesizing vitamin B and vitamin K as well as metabolizing bile acids, sterols, and xenobiotics. 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, and dysregulation of the gut flora has been correlated
with a host of inflammatory and autoimmune conditions.
Composition
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. However, 99% of gut bacteria
come from about 30 or 40 species. Bacteria also make up to 60% of the dry
mass of feces.
Over 99% of
the bacteria in the gut are anaerobes, but in the cecum, aerobic bacteria reach high densities. It
is estimated that the human gut microbiota have around a hundred times as
many genes as there are in the human genome.
In humans,
the gut microbiota has the largest numbers of bacteria and the greatest number
of species compared to other areas of the body. 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.
The
composition of human gut microbiota changes over time, when the diet changes,
and as overall health changes. 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.
The colon, in contrast, contains the highest
microbial density recorded in any habitat on Earth with up to 1012 cells
per gram of intestinal content.
These
bacteria represent between 300 and 1000 different species. However, 99% of the bacteria come from about 30 or 40
species. As a consequence of their abundance in the intestine, bacteria
also make up to 60% of the dry mass of feces. Fungi, protists, archaea, and viruses are
also present in the gut flora, but less is known about their activities.
Over
99% of the bacteria in the gut are anaerobes, but in the cecum, aerobic bacteria reach high densities. It is estimated that these
gut flora have around a hundred times as many genes in total as there are in
the human genome.
Many
species in the gut have not been studied outside of their hosts because most
cannot be cultured. While there are a small number of core species of
microbes shared by most individuals, populations of microbes can vary widely
among different individuals. Within an individual, microbe populations
stay fairly constant over time, even though some alterations may occur with
changes in lifestyle, diet and age.
Types
Bacteria
The
four dominant bacterial phyla in the human gut are-
Most
bacteria belong to the following genera
Other
genera, such as Escherichia
and Lactobacillus, 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.
Fungi
Fungal
genera that have been detected in the gut include
·
Candida
·
Trametes
·
Bullera
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.
Archaea constitute another large class
of gut flora which are important in the metabolism of the bacterial products of
fermentation.
Enterotype
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. There are
indications that long-term diet influences enterotype. Three human enterotypes
have been proposed.
·
Type 1 is characterized
by high levels of Bacteroides
·
Type 2 has few Bacteroides but Prevotella are common
·
Type 3 has high levels
of Ruminococcus
Stomach
Due to the
high acidity of the stomach, most microorganisms cannot survive there. The main
bacterial inhabitants of the stomach include Streptococcus, Staphylococcus, Lactobacillus and
Peptostreptococcus. Helicobacter 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.
Intestines
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. However, in the distal
portion of the small intestine alkaline conditions support gram-negative
bacteria of the Enterobacteriaceae.
The bacterial
flora of the small intestine helps in a wide range of intestinal functions. The
bacterial flora provides regulatory signals that enable the development and
utility of the gut. Overgrowth of bacteria in the small intestine can lead to
intestinal failure. In addition the large intestine contains the largest
bacterial ecosystem in the human body.
About 99% of
the large intestine and feces flora are made up of obligate anaerobes such
as Bacteroides and Bifidobacterium.
Factors that disrupt the microorganism population of the large intestine
include antibiotics, stress, and parasites.
Bacteria make
up most of the flora in the colon and 60% of the dry mass of feces. 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:
Bacteroidota
and Bacillota constitute 90% of the
composition. Somewhere between 300 and 1000 different species 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, with Faecalibacterium prausnitzii (phylum firmicutes) being the
most common species in healthy adults.
Relation with humans
The relationship
between gut flora and humans is not merely commensal (a non-harmful coexistence),
but rather is a mutualistic, symbiotic relationship. Though
people can survive with no gut flora 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.
Extensive
modification and imbalances of the gut microbiota and its microbiome or gene
collection are associated with obesity. However, in certain conditions, some
species are thought to be capable of causing disease by causing infection or increasing cancer risk for the host.
Factors affecting Gut Biome
Age
It has been
demonstrated that there are common patterns of microbiome composition evolution
during life. 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. Much of
the maturation of microbiota into an adult-like configuration happens during
the three first years of life.
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.
Geography
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 different origins.
Also 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.
Nutrition
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.
Malnourished
children also typically have more potentially pathogenic gut flora, and
more yeast in their mouths and throats. Altering diet
may lead to changes in gut microbiota composition and diversity.
Ethnicity
Twelve
microbe families are found varied in abundance based on the race or ethnicity
of the individual. Individuals of the same race or ethnicity have more similar
microbiomes than individuals of different racial backgrounds.
Socioeconomic status
Studies have
demonstrated a link between an individual's socioeconomic
status (SES)
and their gut microbiota.
Functions
(1) Direct defense against pathogens
(2) Fortification of host defense by its
role in developing and maintaining the intestinal
epithelium and
inducing antibody production there
(3) Metabolizing otherwise indigestible compounds
in food
(4) Its role in the gut-brain axis is also proved
(5) Fermenting unused energy substrates
(6) Training the immune system via end products of metabolism
like propionate and acetate,
(7) Preventing growth of harmful species,
(8) Producing vitamins for the host (such
as biotin and vitamin K)
(9) Producing hormones to direct the host
to store fats
Direct inhibition of pathogens
The gut flora
community plays a direct role in defending against pathogens by fully
colonizing 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. 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.
Enteric protection and immune system
In humans, a
gut flora similar to an adult's is formed within one to two years of birth. 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, commensal
microorganisms and also provides a barrier to pathogenic
ones. 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.
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. The GALT that
develops is tolerant to gut flora species, but not to other
microorganisms. 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.
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.
Different bacterial species that appear in gut flora have been shown to be able to drive the immune system to create cytokines selectively; Bacteroides fragilis and some Clostridia species appear to drive an anti-inflammatory response, while some segmented filamentous bacteria drive the production of inflammatory cytokines. Gut flora can also regulate the production of antibodies by the immune system.
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. These signaling molecules interact with B cells to induce class
switching to IgA. 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. Ultimately, IgA maintains a
healthy environment between the host and gut bacteria. These cytokines and
antibodies can have effects outside the gut, in the lungs and other tissues.
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. SCFAs stimulate a rapid
increase in the production of innate immune cells like neutrophils, basophils and eosinophils. These cells are part of the
innate immune system that tries to limit the spread of infection.
Metabolism
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. 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.
Bacteria turn
carbohydrates they ferment into short-chain
fatty acids by
a form of fermentation called saccharolytic fermentation. Products include acetic acid, propionic acid and butyric acid. These materials can be used by
host cells, providing a major source of energy and nutrients.
Gases which
are involved in signaling and may cause flatulence and organic acids, such as lactic acid, are also produced by
fermentation. Acetic acid is used by muscle, propionic acid facilitates liver production
of ATP, and butyric acid provides energy to
gut cells.
Gut flora
also synthesize vitamins like biotin and folate, and facilitate absorption of dietary minerals, including magnesium, calcium, and
iron.
Methanobrevibacter smithii is a member of domain Archaea, and is the most abundant methane producing archaeal species in the human microbiota.
Gut
microbiota also serve as a source of Vitamins K and B12 that are not produced
by the body or produced in little amount.
Pharmacomicrobiomics
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. Since the total
number of microbial and viral cells in the human body (over 100 trillion)
greatly outnumber Homo sapiens cells
(tens of trillions) 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
·
microbial
drug metabolism affecting a drug's clinical efficacy and toxicity profile
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. The microbial
metabolism of drugs can sometimes inactivate the drug.
Probiotics,
prebiotics, synbiotics, and pharmabiotics
Probiotics are microorganisms that are believed to provide
health benefits when consumed.
Prebiotics- These 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.
Synbiotics- It refers to food ingredients or dietary
supplements combining
probiotics and prebiotics in a form of synergism.
Pharmabiotics- The term is used in various ways, to
mean:
a. pharmaceutical
formulations (standardized
manufacturing that can obtain regulatory approval as a drug) of
probiotics, prebiotics, or synbiotics
b. probiotics
that have been genetically engineered or otherwise optimized for best
performance (shelf life, survival in the digestive tract, etc.)
c. the
natural products of gut flora metabolism (vitamins, etc.)
No comments:
Post a Comment