Colonization resistance is the mechanism whereby the human microbiome protects itself against incursion by new and often harmful microorganisms. [1] [2]
Colonization resistance was first identified in 1967, and it was initially referred to as antibiotic associated susceptibility. It was observed that animals being treated with the antibiotic streptomycin were susceptible to Salmonella enterica at doses 10,000 fold lower than the standard minimal infectious dose. [3] This led to investigations about the mechanisms utilized by endogenous microbial populations that conferred protection against exogenous pathogens attempting to colonize the gut flora.
It has been observed that colonization resistance can occur within the host in a 'direct' or 'indirect' manner. [4] The former refers to particular components of the microbiota directly competing with exogenous pathogens for nutritional niches (e.g. E. coli directly competes with Citrobacter rodentium for carbohydrates in the intestinal lumen [5] ) or by producing growth inhibitors (e.g. Bacteroides thuringiensis can secrete bacteriocin that directly targets spore-forming Clostridium difficile , thus inhibiting its growth through an unknown mechanism), [6] that directly inhibits the colonizing pathogen. Indirect colonization resistance is thought to be mediated through the induction of immune responses in the host that concomitantly inhibit the colonizing pathogen. An example of this has been observed with B. thetaiotaomicron, which can induce the host to produce antimicrobial C-type lectins REGIIIγ and REGIIIβ, both anti-microbial peptides that target gram-positive bacteria. [7]
Scientists found that gut infections increase its microbiota's resistance to subsequent infections, that taurine is used in as a nutrient to nourish and train the microbiota for this by potentiating its production of sulfide and that the exogenous supply of taurine can induce this microbiota alteration. [8] [9]
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 gastrointestinal tract, skin, mammary glands, seminal fluid, uterus, ovarian follicles, lung, saliva, oral mucosa, conjunctiva, and the biliary 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.
Clostridioides difficile infection, also known as Clostridium difficile infection, is a symptomatic infection due to the spore-forming bacterium Clostridioides difficile. Symptoms include watery diarrhea, fever, nausea, and abdominal pain. It makes up about 20% of cases of antibiotic-associated diarrhea. Antibiotics can contribute to detrimental changes in gut microbiota; specifically, they decrease short-chain fatty acid absorption which results in osmotic, or watery, diarrhea. Complications may include pseudomembranous colitis, toxic megacolon, perforation of the colon, and sepsis.
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.
Fecal microbiota transplant (FMT), also known as a stool transplant, is the process of transferring fecal bacteria and other microbes from a healthy individual into another individual. FMT is an effective treatment for Clostridioides difficile infection (CDI). For recurrent CDI, FMT is more effective than vancomycin alone, and may improve the outcome after the first index infection.
Virulence factors are cellular structures, molecules and regulatory systems that enable microbial pathogens to achieve the following:
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.
Vaginal flora, vaginal microbiota or vaginal microbiome are the microorganisms that colonize the vagina. They were discovered by the German gynecologist Albert Döderlein in 1892 and are part of the overall human flora. The amount and type of bacteria present have significant implications for an individual's overall health. The primary colonizing bacteria of a healthy individual are of the genus Lactobacillus, such as L. crispatus, and the lactic acid they produce is thought to protect against infection by pathogenic species.
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.
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.
Pediococcus acidilactici is a species of Gram-positive cocci that is often found in pairs or tetrads. P. acidilactici is a homofermentative bacterium that can grow in a wide range of pH, temperature, and osmotic pressure, therefore being able to colonize the digestive tract. It has emerged as a potential probiotic that has shown promising results in animal and human experiments, though some of the results are limited. They are commonly found in fermented vegetables, fermented dairy products, and meat.
Clostridium cadaveris is an enteric, gas-forming, motile, strictly anaerobic gram-positive bacterium of the genus Clostridium. First described by Klein in 1899, it was noted to be the most prominent bacteria during human decomposition; historically it was described as "putrefying flora".
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.
Clostridioides difficile is a bacterium known for causing serious diarrheal infections, and may also cause colon cancer. It is known also as C. difficile, or C. diff, and is a Gram-positive species of spore-forming bacteria. Clostridioides spp. are anaerobic, motile bacteria, ubiquitous in nature and especially prevalent in soil. Its vegetative cells are rod-shaped, pleomorphic, and occur in pairs or short chains. Under the microscope, they appear as long, irregular cells with a bulge at their terminal ends. Under Gram staining, C. difficile cells are Gram-positive and show optimum growth on blood agar at human body temperatures in the absence of oxygen. C. difficile is catalase- and superoxide dismutase-negative, and produces up to three types of toxins: enterotoxin A, cytotoxin B and Clostridioides difficile transferase. Under stress conditions, the bacteria produce spores that are able to tolerate extreme conditions that the active bacteria cannot tolerate.
Proteobiotics are natural metabolites which are produced by fermentation process of specific probiotic strains. These small oligopeptides were originally discovered in and isolated from culture media used to grow probiotic bacteria and may account for some of the health benefits of probiotics.
Janelle S. Ayres is an American immunologist and microbiologist, member of the NOMIS Center for Immunobiology and Microbial Pathogenesis and Helen McLoraine Developmental Chair at the Salk Institute for Biological Sciences. Her research focuses on the relation of host-pathogen interactions with the microbiome.
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.
Trevor Lawley FMedSci is a Faculty member and Group Leader in the Host-Microbiota Interactions Lab at the Wellcome Sanger Institute (WSI). He is also co-founder and Chief Scientific Officer of the biotech company Microbiotica.
The poultry microbiome is an understudied, yet extremely impactful part of the poultry industry. Poultry is defined as any avian species used for production purposes such as food or down feathers. The United States consumes more poultry, specifically broiler meat, than any other type of protein. Worldwide, poultry makes up 33% of consumed meat. This makes poultry extremely valuable and the impact of the poultry microbiome on health and production even more valuable. Antonie van Leeuwenhoek was the first to notice microbes inside animals through stool samples giving light to further research into the gut microbiome. His discovery lead to the ever evolving study of the microbiota and microbiome. The microbiota is the entirety of living organisms including bacteria, viruses, fungi, and archaea in an environment. The microbiome is the combination of the microbiota and the additional activities in that system including metabolites and chemicals in a habitat. Much of the work done to characterize the poultry microbiome has been accomplished over the past decade and was done through the use of 16s rRNA sequencing.