The human microbiome is the aggregate of all microbiota that reside on or within human tissues and biofluids along with the corresponding anatomical sites in which they reside, including the skin, mammary glands, seminal fluid, uterus, ovarian follicles, lung, saliva, oral mucosa, conjunctiva, biliary tract, and gastrointestinal tract. Types of human microbiota include bacteria, archaea, fungi, protists, and viruses. Though micro-animals can also live on the human body, they are typically excluded from this definition. In the context of genomics, the term human microbiome is sometimes used to refer to the collective genomes of resident microorganisms; however, the term human metagenome has the same meaning.
In medicine, the hygiene hypothesis states that early childhood exposure to particular microorganisms protects against allergies by strengthening the immune system. In particular, a lack of such exposure is thought to lead to poor immune tolerance. The time period for exposure begins before birth and ends at school age.
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.
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.
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. Dysbiosis is most commonly reported as a condition in the gastrointestinal tract.
Pyroptosis is a highly inflammatory form of lytic programmed cell death that occurs most frequently upon infection with intracellular pathogens and is likely to form part of the antimicrobial response. This process promotes the rapid clearance of various bacterial, viral, fungal and protozoan infections by removing intracellular replication niches and enhancing the host's defensive responses. Pyroptosis can take place in immune cells and is also reported to occur in keratinocytes and some epithelial cells.
Damage-associated molecular patterns (DAMPs) are molecules within cells that are a component of the innate immune response released from damaged or dying cells due to trauma or an infection by a pathogen. They are also known as danger signals, and alarmins because they serve as warning signs to alert the organism to any damage or infection to its cells. DAMPs are endogenous danger signals that are discharged to the extracellular space in response to damage to the cell from mechanical trauma or a pathogen. Once a DAMP is released from the cell, it promotes a noninfectious inflammatory response by binding to a pattern recognition receptor. Inflammation is a key aspect of the innate immune response; it is used to help mitigate future damage to the organism by removing harmful invaders from the affected area and start the healing process. As an example, the cytokine IL-1α is a DAMP that originates within the nucleus of the cell which, once released to the extracellular space, binds to the PRR IL-1R, which in turn initiates an inflammatory response to the trauma or pathogen that initiated the release of IL-1α. In contrast to the noninfectious inflammatory response produced by DAMPs, pathogen-associated molecular patterns initiate and perpetuate the infectious pathogen-induced inflammatory response. Many DAMPs are nuclear or cytosolic proteins with defined intracellular function that are released outside the cell following tissue injury. This displacement from the intracellular space to the extracellular space moves the DAMPs from a reducing to an oxidizing environment, causing their functional denaturation, resulting in their loss of function. Outside of the aforementioned nuclear and cytosolic DAMPs, there are other DAMPs originated from different sources, such as mitochondria, granules, the extracellular matrix, the endoplasmic reticulum, and the plasma membrane.
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. 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, and while these bacteria can be pathogenic to their host most of them are mutually beneficial to both the host and bacteria.
Inflammasomes are cytosolic multiprotein oligomers of the innate immune system responsible for the activation of inflammatory responses. Activation and assembly of the inflammasome promotes proteolytic cleavage, maturation and secretion of pro-inflammatory cytokines interleukin 1β (IL-1β) and interleukin 18 (IL-18), as well as cleavage of gasdermin D. The N-terminal fragment resulting from this cleavage induces a pro-inflammatory form of programmed cell death distinct from apoptosis, referred to as pyroptosis, and is responsible for secretion of the mature cytokines, presumably through the formation of pores in the plasma membrane. Additionally, inflammasomes can be incorporated into larger cell death-inducing complexes called PANoptosomes, which drive another distinct form of pro-inflammatory cell death called PANoptosis.
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.
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.
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.
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.
Metatranscriptomics is the set of techniques used to study gene expression of microbes within natural environments, i.e., the metatranscriptome.
Yasmine Belkaid is an Algerian immunologist and senior investigator at the National Institute of Allergy and Infectious Diseases (NIAID) and adjunct professor at the University of Pennsylvania. She is best known for her work studying host-microbe interactions in tissues and immune regulation to microbes. Belkaid currently serves as the director of the NIAID Microbiome program. On 29 March 2023, she was appointed as President of the Pasteur Institute for a six-year term, starting from January 2024.
Inflammaging is a chronic, sterile, low-grade inflammation that develops with advanced age, in the absence of overt infection, and may contribute to clinical manifestations of other age-related pathologies. Inflammaging is thought to be caused by a loss of control over systemic inflammation resulting in chronic overstimulation of the innate immune system. Inflammaging is a significant risk factor in mortality and morbidity in aged individuals.
Thirumala-Devi Kanneganti is an immunologist and is the Rose Marie Thomas Endowed Chair, Vice Chair of the Department of Immunology, and Member at St. Jude Children's Research Hospital. She is also Director of the Center of Excellence in Innate Immunity and Inflammation at St. Jude Children's Research Hospital. Her research interests include investigating fundamental mechanisms of innate immunity, including inflammasomes and inflammatory cell death, PANoptosis, in infectious and inflammatory disease and cancer.
Eran Elinav is an Israeli immunologist and microbiota researcher at the Weizmann Institute of Science and the DKFZ.
Eric P. Skaar is an American microbiologist, the Ernest W. Goodpasture Professor of Pathology, Microbiology and Immunology at Vanderbilt University Medical Center, and a University Distinguished Professor at Vanderbilt University.
A pathobiont is an organism that is native to the host's microbiome that under certain environmental or genetic changes can become pathogenic and induce disease.
