Microbial symbiosis and immunity

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MRSA (yellow) enguled by neutrophil (purple) Photo Source: National Institute of Allergy and Infectious Diseases MRSA, Ingestion by Neutrophil.jpg
MRSA (yellow) enguled by neutrophil (purple) Photo Source: National Institute of Allergy and Infectious Diseases

Long-term close-knit interactions between symbiotic microbes and their host can alter host immune system responses to other microorganisms, including pathogens, and are required to maintain proper homeostasis. [1] The immune system is a host defense system consisting of anatomical physical barriers as well as physiological and cellular responses, which protect the host against harmful microorganisms while limiting host responses to harmless symbionts. Humans are home to 1013 to 1014 bacteria, roughly equivalent to the number of human cells, [2] and while these bacteria can be pathogenic to their host most of them are mutually beneficial to both the host and bacteria.

Contents

The human immune system consists of two main types of immunity: innate and adaptive. The innate immune system is made of non-specific defensive mechanisms against foreign cells inside the host including skin as a physical barrier to entry, activation of the complement cascade to identify foreign bacteria and activate necessary cell responses, and white blood cells that remove foreign substances. The adaptive immune system, or acquired immune system, is a pathogen-specific immune response that is carried out by lymphocytes through antigen presentation on MHC molecules to distinguish between self and non-self antigens.

Microbes can promote the development of the host's immune system in the gut and skin, and may help to prevent pathogens from invading. Some release anti-inflammatory products, protecting against parasitic gut microbes. Commensals promote the development of B cells that produce a protective antibody, Immunoglobulin A (IgA). This can neutralize pathogens and exotoxins, and promote the development of immune cells and mucosal immune response. However, microbes have been implicated in human diseases including inflammatory bowel disease, obesity, and cancer.

General principles

Microbial symbiosis relies on interspecies communication. [3] between the host and microbial symbionts. Immunity has been historically characterized in multicellular organisms as being controlled by the host immune system, where a perceived foreign substance or cell stimulates an immune response. The end result of this response can vary from clearing of a harmful pathogen to tolerance of a beneficial microbe to an autoimmune response that harms the host itself.

Symbiotic microorganisms have more recently been shown to also be involved in this immune response indicating that the immune response is not isolated to host cells alone. These beneficial microorganisms have been implicated in inhibiting growth of pathogens in the gut and anti-cancer immunity among other responses.

Gastrointestinal tract

Clostridium difficile from stool sample Clostridium difficile 01.jpg
Clostridium difficile from stool sample

The human gastrointestinal tract (GI tract) consists of the mouth, pharynx, esophagus, stomach, small intestine, and large intestine, and is a 9-meter-long continuous tube; the largest body surface area exposed to the external environment. The intestine offers nutrients and protection to microbes, enabling them to thrive with an intestinal microbial community of 1014 beneficial and pathogenic bacteria, archaea, viruses, and eukaryotes. In return many of these microbes complete important functions for the host including breakdown of fiber [4] and production of vitamins [5] where gut microbes have at least a role in the production of vitamins such as A, B2, B3, B5, B12, C, D and K.

In the human gut the immune system comes into contact with a large number of foreign microbes, both beneficial and pathogenic. The immune system is capable of protecting the host from these pathogenic microbes without starting unnecessary and harmful immune responses to stimuli. The gastrointestinal microbiota has a direct effect on the human body's immune responses. meaning a regular microbiota is necessary for a healthy host immune system as the body is more susceptible to infectious and non-infectious diseases.

Regulation of immune responses

Commensal bacteria in the GI tract survive despite the abundance of local immune cells. [6] Homeostasis in the intestine requires stimulation of toll-like receptors by commensal microbes. [6] When mice are raised in germ-free conditions, they lack circulating antibodies, and cannot produce mucus, antimicrobial proteins, or mucosal T-cells. [6] Additionally, mice raised in germ-free conditions lack tolerance and often suffer from hypersensitivity reactions. [6] Maturation of the GI tract is mediated by pattern recognition receptors (PRRs), which recognize non-self pathogen associated molecular patterns (PAMPs) including bacterial cell wall components and nucleic acids. [7] These data suggest that commensal microbes aid in intestinal homeostasis and immune system development. [6]

To prevent constant activation of immune cells and resulting inflammation, hosts and bacteria have evolved to maintain intestinal homeostasis and immune system development. [8] For example, the human symbiont Bacteroides fragilis produces polysaccharide A (PSA), which binds to toll-like receptor 2 (TLR-2) on CD4+ T cells. [9] While TLR2 signaling can activate clearance of peptides, PSA induces an anti-inflammatory response when it binds to TLR2 on CD4+ T cells. [9] Through TLR2 binding, PSA suppresses pro-inflammatory TH17 responses, promoting tolerance and establishing commensal gut colonization. [9]

Commensal gut microbes create a variety of metabolites that bind aryl hydrocarbon receptors (AHR). AHR is a ligand-inducible transcription factor found in immune and epithelial cells and binding of AHR is required for normal immune activation as the lack of AHR binding has been shown to cause over activation of immune cells. [1] These microbial metabolites are crucial for protecting the host from unnecessary inflammation in the gut.

Development of isolated lymphoid tissues

Microbes trigger development of isolated lymphoid follicles in the small intestine of humans and mice, which are sites of mucosal immune response. Isolated lymphoid follicles (ILFs) collect antigens through M cells, develop germinal centers, and contain many B cells. [10] Gram-negative commensal bacteria trigger the development of inducible lymphoid follicles by releasing peptidogylcans containing diaminopimelic acid during cell division. [10] The peptidoglycans bind to the NOD1 receptor on intestinal epithelial cells. [10] As a result, the intestinal epithelial cells express chemokine ligand 20 (CCL20) and Beta defensin 3. [10] CCL20 and Beta-defensin 3 activate cells which mediate the development of isolated lymphoid tissues, including lymphoid tissue inducer cells and lymphoid tissue organizer cells. [10]

Additionally, there are other mechanisms by which commensals promote maturation of isolated lymphoid follicles. For example, commensal bacteria products bind to TLR2 and TLR4, which results in NF-κB mediated transcription of TNF, which is required for the maturation of mature isolated lymphoid follicles. [11]

Protection against pathogens

Microbes can prevent growth of harmful pathogens by altering pH, consuming nutrients required for pathogen survival, and secreting toxins and antibodies that inhibit growth of pathogens. [12]

Immunoglobulin A

IgA prevents entry and colonization of pathogenic bacteria in the gut. It can be found as a monomer, dimer, or tetramer, allowing it to bind multiple antigens simultaneously. [13] IgA coats pathogenic bacterial and viral surfaces (immune exclusion), preventing colonization by blocking their attachment to mucosal cells, and can also neutralize PAMPs. [8] [14] IgA promotes the development of TH17 and FOXP3+ regulatory T cells. [15] [16] Given its critical function in the GI tract, the number of IgA-secreting plasma cells in the jejunum is greater than the total plasma cell population of the bone marrow, lymph, and spleen combined. [13]

Microbiota-derived signals recruit IgA-secreting plasma cells to mucosal sites. [8] For example, bacteria on the apical surfaces of epithelial cells are phagocytosed by dendritic cells located beneath peyer's patches and in the lamina propria, ultimately leading to differentiation of B cells into plasma cells that secrete IgA specific for intestinal bacteria. [17] The role of microbiota-derived signals in recruiting IgA-secreting plasma cells was confirmed in experiments with antibiotic-treated specific pathogen free and MyD88 KO mice, which have limited commensals and a decreased ability to respond to commensals. The number of intestinal CD11b+ IgA+ plasma cells was reduced in these mice, suggesting the role of commensals in recruiting IgA-secreting plasma cells. [18] Based on this evidence commensal microbes can protect the host from harmful pathogens by stimulating IgA production.

Antimicrobial peptides

Nisin amino acid structure Nisin 2d amino structure.JPG
Nisin amino acid structure

Members of the microbiota are capable of producing antimicrobial peptides, protecting humans from excessive intestinal inflammation and microbial-associated diseases. Various commensals (primarily Gram-positive bacteria), secrete bacteriocins, peptides which bind to receptors on closely related target cells, forming ion-permeable channels and pores in the cell wall. [19] The resulting efflux of metabolites and cell contents and dissipation of ion gradients causes bacterial cell death. [19] However, bacteriocins can also induce death by translocating into the periplasmic space and cleaving DNA non-specifically (colicin E2), inactivating the ribosome (colicin E3), inhibiting synthesis of peptidoglycan, a major component of the bacterial cell wall (colicin M). [19]

Bacteriocins have immense potential to treat human disease. For example, diarrhea in humans can be caused by a variety of factors, but is often caused by bacteria such as Clostridium difficile. [19] Microbispora strain ATCC PTA-5024 secretes the bacteriocin microbisporicin, which kills Clostridia by targeting prostaglandin synthesis. [20] Additionally, bacteriocins are particularly promising due to their difference in mechanisms than antibiotics meaning many antibiotic-resistant bacteria are not resistant to these bacteriocins. For example, in vitro growth of methicillin-resistant S. aureus (MRSA) was inhibited by the bacteriocin nisin A, produced by Lactococcus lactis. [19] [21] Nisin A inhibits methicillin-resistant S. aureus by binding to the precursor to bacterial cell wall synthesis, lipid II. This hinders the ability to synthesize the cell wall, resulting in increased membrane permeability, disruption of electrochemical gradients, and possible death. [22]

Fortification fucose

The intestinal epithelium in humans is reinforced with carbohydrates like fucose expressed on the apical surface of epithelial cells. [23] Bacteroides thetaiotaomicron , a bacterial species in the ileum and colon, stimulates the gene encoding fucose, Fut2, in intestinal epithelial cells. [23] In this mutualistic interaction, the intestinal epithelial barrier is fortified and humans are protected against invasion of destructive microbes, while B. thetaiotaomicron benefits because of it can use fucose for energy production and its role in bacterial gene regulation. [23]

Skin

Staphylococcus epidermidis under a scanning electron microscope Staphylococcus epidermidis lores.jpg
Staphylococcus epidermidis under a scanning electron microscope

The skin microbiota is vital as a line of defense against infection, a physical barrier between the environment and the inside of the host. Commensal microbes that live on the skin, such as Staphylococcus epidermidis, produce antimicrobial peptides (AMPs) that aid the host immune system. [24] These AMPs signal immune responses and maintain an inflammatory homeostasis by modulating the release of cytokines. [24] S. epidermidis secretes a small molecule AMP which leads to increased expression of Human β-defensins. [24] S.epidermidis also stimulates IL-17A+ CD8+ T cells production that increases host immunity. [25]

Exposure to these skin commensal bacteria early in development is crucial for host tolerance of these microbes as T cell encounters allow commensal antigen presentation to be common during development. [26] S. epidermidis and other important microflora work similarly to support homeostasis and general health in areas all over the human body such as the oral cavity, vagina, gastrointestinal tract, and oropharynx. [24]

Role in disease

An equilibrium of  symbionts  and pathobionts is critical to fight off outside pathogens and avoid many harmful disorders. Dysbiosis, or imbalances in the bacterial composition of the intestine, has been implicated in inflammatory bowel disease, obesity, and allergic diseases in humans and other animals. [27]

Cancer

Killer T-cells surround cancer cell Killer T cells surround a cancer cell.png
Killer T-cells surround cancer cell

Gut microbes may play a role in cancer development through a variety of mechanisms. Sulfate-reducing bacteria produce hydrogen sulfide, which results in genomic DNA damage. [28] Higher rates of colon cancer are associated with higher amounts of sulfate-reducing bacteria in the gut. [28] Additionally, anaerobic bacteria in the colon transform primary bile acids into secondary bile acid which has been implicated in colorectal carcinogenesis. [28] Gut bacteria metabolites such as short-chain fatty acids (SCFAs), B vitamins and N1, N12-diacetylspermine have also been implicated in suppressing colorectal cancer. [1] Gram-negative bacteria produce lipopolysaccharide (LPS), which binds to TLR-4 and through TGF-β signaling, leads to the expression of growth factors and inflammatory mediators that promote neoplasia. [28]

Members of a healthy gut microbiome have been shown to increase interferon-γ-producing CD8 T-cells and tumor-infiltrating dendritic cells (TILs) in the intestine. [29] Not only do these CD8 T-cells enhance resistance against intracellular pathogens such as Listeria monocytogenes but they also have been shown to be important in anti-cancer immunity specifically against MC38 adenocarcinoma where they along with the TILs increase MHC I expression. [29]

Allergic and immune disorders

Figure A shows the location of the lungs and airways in the body. Figure B shows a cross-section of a normal airway. Figure C shows a cross-section of an airway during asthma symptoms. Asthma attack-illustration NIH.jpg
Figure A shows the location of the lungs and airways in the body. Figure B shows a cross-section of a normal airway. Figure C shows a cross-section of an airway during asthma symptoms.

The human microbiome modulates the host immune in positive ways to help defend itself from potential pathogens but can also lead to immune overreactions to foreign substances, even sometimes attacking the host itself. Inflammatory bowel disease (IBD) and asthma are two disorders that have been found to be impacted by microbiota metabolites causing immune reactions. Short-chain fatty acids (SCFAs) have been linked to a decrease in allergic inflammation in asthma [30] while both SCFAs and B vitamins have been shown to decrease IBD inflammation. [31]

SCFAs (acetate, butyrate and propionate) are metabolites created by bacteria in the gut, these molecules then inhibit histone deacetylases (HDACs) as well as G protein-coupled receptors, acting as signaling molecules. [1] Inhibition of HDACs downregulates nuclear factor-κB (NF-κB) and the pro-inflammatory tumor necrosis factor (TNF) as well as having anti-inflammatory effects on macrophages and dendritic cells. [1]

Activation of mucosal immunity and the intestinal microbiota may contribute to inflammatory bowel disease. Many bacteria cause inflammation in the gut including Escherichia coli, which replicate in macrophages and secretes cytokine tumor necrosis factor. [32] However, some bacteria, including the human symbiont B. fragilis, may prevent colitis by producing polysaccharide A (PSA). [33] PSA induces production of IL-10, an immunosuppressive cytokine that suppresses inflammation. [34] Treatment of bone-marrow-derived dendritic cells and naïve CD4+ T cells with purified PSA resulted in increased IL-10 production. [34]

To mimic colitis and activate inflammatory T cells in an experimental condition, wild-type mice were treated with trinitrobenzen sulphonic acid (TNBS). [34] Thereafter, these mice were given PSA orally. Pro-inflammatory cytokine expression (IL-17a and TNFα) in CD4+ cells was measured with ELISA. The researchers found that compared to the CD4+ cells in the control mice, CD4+ cells in PSA-treated mice produced reduced levels of the pro-inflammatory cytokines IL-17a and TNFα. [34] Furthermore, after intestinal colonization with B. fragilis, IL-23 expression by splenocytes was markedly reduced. [34] These data suggest that PSA secreted by B. fragilis suppresses the inflammatory process during colitis by leading to increased production of IL-10 and decreased production of IL-17, TNFα, and IL-23. [34]

Commensal bacteria may also regulate immune responses that cause allergies. For example, commensal bacteria stimulate TLR4, which may inhibit allergic responses to food. [35]

Metabolic disorders

Major metabolic diseases have been found to be impacted by gut microbiota metabolites, including heart disease, kidney disease, type 2 diabetes and obesity. [1] Breakdown of L-carnitine from red meat by gut microbes into trimethylamine N-oxide (TMAO) has been associated with atherosclerosis, which can lead to obesity, heart disease and type 2 diabetes [36] while both heart and kidney disease events can be predicted by high free p-Cresol levels. [37] SCFAs modulates renin secretion by binding Olfr78, lowering blood pressure and decreasing the risk of kidney disease. [38]

Studies with germ-free mice have suggested that the absence of gut microbes protects against obesity. [39] While the exact mechanism by which microbes play a role in obesity has yet to be elucidated, it has been hypothesized that the intestinal microbiota is involved in converting food to usable energy and fat storage. [39]

Neurological disorders

Gut microbiota impacts many facets of human health, even neurological disorders that can be caused by molecule or hormone imbalance. Autism spectrum disorder (ASD), [1] central nervous system dysfunction [1] and depression [40] have all been found to be impacted by the microbiota.

Blood-brain barrier transport Blood-brain barrier transport en.png
Blood-brain barrier transport

While ASD is regularly described by behavioral differences it also can present with gastrointestinal symptoms. [41] Dysbiosis of the GI tract has been noted in some ASD individuals, leading to an increased intestinal permeability. [41] In the mouse model mice with ASD and GI tract dysbiosis (maternal immune activation) increased intestinal permeability was found as was corrected by the introduction of human gut bacterial symbiont B. fragilis. [41]

Microglia development have a pivotal role in central nervous system dysfunction, bacterial metabolite SCFAs regulate microglia homeostasis that is crucial for regular CNS development. [42] Also pivotal for brain development is the creation of tight junctions at the blood-brain barrier in order to control passage between the blood and brain. Germ-free mice have increased blood-brain barrier permeability due to decreased expression of tight junction proteins occludin and claudin-5 as compared to normal gut microbiota mice. [43]

Butyrate-producing bacteria and the dopamine metabolite 3,4-dihydroxyphenylacetic acid have been linked to higher quality of life indicators while γ-aminobutyric acid has been linked to higher levels of depression. [40]

Related Research Articles

<span class="mw-page-title-main">Immunoglobulin A</span> Antibody that plays a crucial role in the immune function of mucous membranes

Immunoglobulin A is an antibody that plays a role in the immune function of mucous membranes. The amount of IgA produced in association with mucosal membranes is greater than all other types of antibody combined. In absolute terms, between three and five grams are secreted into the intestinal lumen each day. This represents up to 15% of total immunoglobulins produced throughout the body.

Gut-associated lymphoid tissue (GALT) is a component of the mucosa-associated lymphoid tissue (MALT) which works in the immune system to protect the body from invasion in the gut.

<span class="mw-page-title-main">Gut microbiota</span> Community of microorganisms in the gut

Gut microbiota, gut microbiome, or gut flora are the microorganisms, including bacteria, archaea, fungi, and viruses, that live in the digestive tracts of animals. The gastrointestinal metagenome is the aggregate of all the genomes of the gut microbiota. The gut is the main location of the human microbiome. 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.

<span class="mw-page-title-main">Paneth cell</span> Anti-microbial epithelial cell of the small intestine

Paneth cells are cells in the small intestine epithelium, alongside goblet cells, enterocytes, and enteroendocrine cells. Some can also be found in the cecum and appendix. They are located below the intestinal stem cells in the intestinal glands and the large eosinophilic refractile granules that occupy most of their cytoplasm.

Immune tolerance, also known as immunological tolerance or immunotolerance, refers to the immune system's state of unresponsiveness to substances or tissues that would otherwise trigger an immune response. It arises from prior exposure to a specific antigen and contrasts the immune system's conventional role in eliminating foreign antigens. Depending on the site of induction, tolerance is categorized as either central tolerance, occurring in the thymus and bone marrow, or peripheral tolerance, taking place in other tissues and lymph nodes. Although the mechanisms establishing central and peripheral tolerance differ, their outcomes are analogous, ensuring immune system modulation.

Microfold cells are found in the gut-associated lymphoid tissue (GALT) of the Peyer's patches in the small intestine, and in the mucosa-associated lymphoid tissue (MALT) of other parts of the gastrointestinal tract. These cells are known to initiate mucosal immunity responses on the apical membrane of the M cells and allow for transport of microbes and particles across the epithelial cell layer from the gut lumen to the lamina propria where interactions with immune cells can take place.

Dysbiosis is characterized by a disruption to the microbiome resulting in an imbalance in the microbiota, changes in their functional composition and metabolic activities, or a shift in their local distribution. For example, a part of the human microbiota such as the skin flora, gut flora, or vaginal flora, can become deranged, with normally dominating species underrepresented and normally outcompeted or contained species increasing to fill the void. Similar to the human gut microbiome, diverse microbes colonize the plant rhizosphere, and dysbiosis in the rhizosphere, can negatively impact plant health. Dysbiosis is most commonly reported as a condition in the gastrointestinal tract or plant rhizosphere.

<span class="mw-page-title-main">Intraepithelial lymphocyte</span>

Intraepithelial lymphocytes (IEL) are lymphocytes found in the epithelial layer of mammalian mucosal linings, such as the gastrointestinal (GI) tract and reproductive tract. However, unlike other T cells, IELs do not need priming. Upon encountering antigens, they immediately release cytokines and cause killing of infected target cells. In the GI tract, they are components of gut-associated lymphoid tissue (GALT).

<span class="mw-page-title-main">Microbiota</span> Community of microorganisms

Microbiota are the range of microorganisms that may be commensal, mutualistic, or pathogenic found in and on all multicellular organisms, including plants. Microbiota include bacteria, archaea, protists, fungi, and viruses, and have been found to be crucial for immunologic, hormonal, and metabolic homeostasis of their host.

<span class="mw-page-title-main">Mucosal immunology</span> Field of study

Mucosal immunology is the study of immune system responses that occur at mucosal membranes of the intestines, the urogenital tract, and the respiratory system. The mucous membranes are in constant contact with microorganisms, food, and inhaled antigens. In healthy states, the mucosal immune system protects the organism against infectious pathogens and maintains a tolerance towards non-harmful commensal microbes and benign environmental substances. Disruption of this balance between tolerance and deprivation of pathogens can lead to pathological conditions such as food allergies, irritable bowel syndrome, susceptibility to infections, and more.

Segmented filamentous bacteria or CandidatusSavagella are members of the gut microbiota of rodents, fish and chickens, and have been shown to potently induce immune responses in mice. They form a distinct lineage within the Clostridiaceae and the name Candidatus Savagella has been proposed for this lineage.

The lung microbiota is the pulmonary microbial community consisting of a complex variety of microorganisms found in the lower respiratory tract particularly on the mucous layer and the epithelial surfaces. These microorganisms include bacteria, fungi, viruses and bacteriophages. The bacterial part of the microbiota has been more closely studied. It consists of a core of nine genera: Prevotella, Sphingomonas, Pseudomonas, Acinetobacter, Fusobacterium, Megasphaera, Veillonella, Staphylococcus, and Streptococcus. They are aerobes as well as anaerobes and aerotolerant bacteria. The microbial communities are highly variable in particular individuals and compose of about 140 distinct families. The bronchial tree for instance contains a mean of 2000 bacterial genomes per cm2 surface. The harmful or potentially harmful bacteria are also detected routinely in respiratory specimens. The most significant are Moraxella catarrhalis, Haemophilus influenzae, and Streptococcus pneumoniae. They are known to cause respiratory disorders under particular conditions namely if the human immune system is impaired. The mechanism by which they persist in the lower airways in healthy individuals is unknown.

Colonization resistance is the mechanism whereby the intestinal microbiota protects itself against incursion by new and often harmful microorganisms.

Innate lymphoid cells (ILCs) are the most recently discovered family of innate immune cells, derived from common lymphoid progenitors (CLPs). In response to pathogenic tissue damage, ILCs contribute to immunity via the secretion of signalling molecules, and the regulation of both innate and adaptive immune cells. ILCs are primarily tissue resident cells, found in both lymphoid, and non- lymphoid tissues, and rarely in the blood. They are particularly abundant at mucosal surfaces, playing a key role in mucosal immunity and homeostasis. Characteristics allowing their differentiation from other immune cells include the regular lymphoid morphology, absence of rearranged antigen receptors found on T cells and B cells, and phenotypic markers usually present on myeloid or dendritic cells.

Skin immunity is a property of skin that allows it to resist infections from pathogens. In addition to providing a passive physical barrier against infection, the skin also contains elements of the innate and adaptive immune systems which allows it to actively fight infections. Hence the skin provides defense in depth against infection.

The altered Schaedler flora (ASF) is a community of eight bacterial species: two lactobacilli, one Bacteroides, one spiral bacterium of the Flexistipes genus, and four extremely oxygen sensitive (EOS) fusiform-shaped species. The bacteria are selected for their dominance and persistence in the normal microflora of mice, and for their ability to be isolated and grown in laboratory settings. Germ-free animals, mainly mice, are colonized with ASF for the purpose of studying the gastrointestinal (GI) tract. Intestinal mutualistic bacteria play an important role in affecting gene expression of the GI tract, immune responses, nutrient absorption, and pathogen resistance. The standardized microbial cocktail enabled the controlled study of microbe and host interactions, role of microbes, pathogen effects, and intestinal immunity and disease association, such as cancer, inflammatory bowel disease, diabetes, and other inflammatory or autoimmune diseases. Also, compared to germfree animals, ASF mice have fully developed immune system, resistance to opportunistic pathogens, and normal GI function and health, and are a great representation of normal mice.

<span class="mw-page-title-main">Intestinal mucosal barrier</span>

The intestinal mucosal barrier, also referred to as intestinal barrier, refers to the property of the intestinal mucosa that ensures adequate containment of undesirable luminal contents within the intestine while preserving the ability to absorb nutrients. The separation it provides between the body and the gut prevents the uncontrolled translocation of luminal contents into the body proper. Its role in protecting the mucosal tissues and circulatory system from exposure to pro-inflammatory molecules, such as microorganisms, toxins, and antigens is vital for the maintenance of health and well-being. Intestinal mucosal barrier dysfunction has been implicated in numerous health conditions such as: food allergies, microbial infections, irritable bowel syndrome, inflammatory bowel disease, celiac disease, metabolic syndrome, non-alcoholic fatty liver disease, diabetes, and septic shock.

<span class="mw-page-title-main">Type 3 innate lymphoid cells</span>

Type 3 innate lymphoid cells (ILC3) are immune cells from the lymphoid lineage that are part of the innate immune system. These cells participate in innate mechanisms on mucous membranes, contributing to tissue homeostasis, host-commensal mutualism and pathogen clearance. They are part of a heterogeneous group of innate lymphoid cells, which is traditionally divided into three subsets based on their expression of master transcription factors as well as secreted effector cytokines - ILC1, ILC2 and ILC3.

<i>Bacteroides thetaiotaomicron</i> Species of bacterium

Bacteroides thetaiotaomicron is a gram-negative, rod shaped obligate anaerobic bacterium that is a prominent member of the normal gut microbiome in the distal intestines. Its proteome, consisting of 4,779 members, includes a system for obtaining and breaking down dietary polysaccharides that would otherwise be difficult to digest. B. thetaiotaomicron is also an opportunistic pathogen, meaning it may become virulent in immunocompromised individuals. It is often used in research as a model organism for functional studies of the human microbiota.

<span class="mw-page-title-main">Yasmine Belkaid</span> Algerian immunologist

Yasmine Belkaid is an immunologist, currently President of the Institut Pasteur. She has Algerian citizenship by her father and French citizenship by her mother, and she also holds US citizenship.

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