The human microbiome is the aggregate of all microbiota that reside on or within and along with the corresponding anatomical sites in which they reside, including the gastrointestinal tract, Human skin, , seminal fluid, uterus, , lung, saliva, oral mucosa, conjunctiva, and the biliary tract. Types of human microbiota include Bacterium, archaea, Fungus, , and viruses. Though 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 of resident microorganisms;
The human body hosts many microorganisms, with approximately the same order of magnitude of non-human cells as human cells. Some microorganisms that humans host are commensalism, meaning they co-exist without harming humans; others have a mutualistic relationship with their human hosts. Conversely, some non-pathogenic microorganisms can harm human hosts via the metabolites they produce, like trimethylamine, which the human body converts to trimethylamine N-oxide via FMO3-mediated oxidation. Certain microorganisms perform tasks that are known to be useful to the human host, but the role of most of them is not well understood. Those that are expected to be present, and that under normal circumstances do not cause disease, are sometimes deemed normal flora or normal microbiota.
During early life, the establishment of a diverse and balanced human microbiota plays a critical role in shaping an individual's long-term health.Smith A, et al. (2019). "The role of the microbiota in the development of allergies and asthma." Current Allergy and Asthma Reports, 19(8), 38. Studies have shown that the composition of the gut microbiota during infancy is influenced by various factors, including mode of delivery, breastfeeding, and exposure to environmental factors.Jackson KD, et al. (2016). "Gut microbiota associations with common diseases and prescription medications in a population-based cohort." Nature Communications, 7, 11622. There are several beneficial species of bacteria and potential probiotics present in breast milk. Research has highlighted the beneficial effects of a healthy microbiota in early life, such as the promotion of immune system development, regulation of metabolism, and protection against pathogenic microorganisms.Yatsunenko T, et al. (2012). "Human gut microbiome viewed across age and geography." Nature, 486(7402), 222-227. Understanding the complex interplay between the human microbiota and early life health is crucial for developing interventions and strategies to support optimal microbiota development and improve overall health outcomes in individuals.Sjögren YM, et al. (2009). "Influence of early gut microbiota on the maturation of childhood mucosal and systemic immune responses." Clinical and Experimental Allergy, 39(12), 1842-1851.
The Human Microbiome Project (HMP) took on the project of sequencing the genome of the human microbiota, focusing particularly on the microbiota that normally inhabit the skin, mouth, nose, digestive tract, and vagina. It reached a milestone in 2012 when it published its initial results.
Aside from simply elucidating the composition of the human microbiome, one of the major questions involving the human microbiome is whether there is a "core", that is, whether there is a subset of the community that is shared among most humans. If there is a core, then it would be possible to associate certain community compositions with disease states, which is one of the goals of the HMP. It is known that the human microbiome (such as the gut microbiota) is highly variable both within a single subject and among different individuals, a phenomenon which is also observed in mice.
On 13 June 2012, a major milestone of the HMP was announced by the National Institutes of Health (NIH) director Francis Collins. The announcement was accompanied with a series of coordinated articles published in Nature and several journals in the Public Library of Science (PLoS) on the same day. By mapping the normal microbial make-up of healthy humans using genome sequencing techniques, the researchers of the HMP have created a reference database and the boundaries of normal microbial variation in humans. From 242 healthy U.S. volunteers, more than 5,000 samples were collected from tissues from 15 (men) to 18 (women) body sites such as mouth, nose, skin, lower intestine (stool), and vagina. All the DNA, human and microbial, were analyzed with DNA sequencing machines. The microbial genome data were extracted by identifying the bacterial specific ribosomal RNA, 16S rRNA. The researchers calculated that more than 10,000 microbial species occupy the human ecosystem, and they have identified 81–99% of the genera.
Once a metagenome is assembled, it is possible to infer the functional potential of the microbiome. The computational challenges for this type of analysis are greater than for single genomes, because usually metagenomes assemblers have poorer quality, and many recovered are non-complete or fragmented. After the gene identification step, the data can be used to carry out a functional annotation by means of multiple alignment of the target genes against orthologs databases.
Marker gene analysis can be influenced by the primer choice; in this kind of analysis, it is desirable to use a well-validated protocol (such as the one used in the Earth Microbiome Project). The first thing to do in a marker gene amplicon analysis is to remove sequencing errors; a lot of sequencing platforms are very reliable, but most of the apparent sequence diversity is still due to errors during the sequencing process. To reduce this phenomenon a first approach is to cluster sequences into Operational taxonomic unit (OTUs): this process consolidates similar sequences (a 97% similarity threshold is usually adopted) into a single feature that can be used in further analysis steps; this method however would discard SNPs because they would get clustered into a single OTU. Another approach is Oligotyping, which includes position-specific information from 16s rRNA sequencing to detect small nucleotide variations and from discriminating between closely related distinct taxa. These methods give as an output a table of DNA sequences and counts of the different sequences per sample rather than OTU.
Another important step in the analysis is to assign a taxonomic name to microbial sequences in the data. This can be done using machine learning approaches that can reach an accuracy at genus-level of about 80%. Other popular analysis packages provide support for taxonomic classification using exact matches to reference databases and should provide greater specificity, but poor sensitivity. Unclassified microorganism should be further checked for organelle sequences.
Phylogenetic aware distance is usually performed with UniFrac or similar tools, such as Soresen's index or Rao's D, to quantify the differences between the different communities. All this methods are negatively affected by horizontal gene transmission (HGT), since it can generate errors and lead to the correlation of distant species. There are different ways to reduce the negative impact of HGT: the use of multiple genes or computational tools to assess the probability of putative HGT events.
The Human Microbiome Project found that individuals host thousands of bacterial types, different body sites having their own distinctive communities. Skin and vaginal sites showed smaller diversity than the mouth and gut, these showing the greatest richness. The bacterial makeup for a given site on a body varies from person to person, not only in type, but also in abundance. Bacteria of the same species found throughout the mouth are of multiple subtypes, preferring to inhabit distinctly different locations in the mouth. Even the enterotypes in the human gut, previously thought to be well understood, are from a broad spectrum of communities with blurred taxon boundaries. PLoS Human Microbiome Project Collection Manuscript Summaries 13 June 2012
It is estimated that 500 to 1,000 species of bacteria live in the human gut but belong to just a few phyla: Bacillota and Bacteroidota dominate but there are also Pseudomonadota, Verrucomicrobiota, Actinobacteriota, Fusobacteriota, and "Cyanobacteria".
A number of types of bacteria, such as Actinomyces viscosus and A. naeslundii, live in the mouth, where they are part of a sticky substance called Dental plaque. If this is not removed by brushing, it hardens into calculus (also called tartar). The same bacteria also secrete acids that dissolve tooth enamel, causing tooth decay.
The Vaginal flora consist mostly of various lactobacillus species. It was long thought that the most common of these species was Lactobacillus acidophilus, but it has later been shown that L. iners is in fact most common, followed by L. crispatus. Other lactobacilli found in the vagina are L. jensenii, L. delbruekii and L. gasseri. Disturbance of the vaginal flora can lead to infections such as bacterial vaginosis and candidiasis.
As of 2007, no clear examples of archaeal were known, although a relationship has been proposed between the presence of some methanogens and human periodontal disease. Methane-dominant small intestinal bacterial overgrowth (SIBO) is also predominantly caused by methanogens, and Methanobrevibacter smithii in particular.
In January 2024, biologists reported the discovery of "obelisks", a new class of viroid, and "oblins", their related group of proteins, in the human microbiome.
The skin acts as a barrier to deter the invasion of pathogenic microbes. The human skin contains microbes that reside either in or on the skin and can be residential or transient. Resident microorganism types vary in relation to skin type on the human body. A majority of microbes reside on superficial cells on the skin or prefer to associate with glands. These glands such as oil or sweat glands provide the microbes with water, amino acids, and fatty acids. In addition, resident bacteria that associated with oil glands are often Gram-positive and can be pathogenic.
The relationship between some gut microbiota and humans is not merely commensalism (a non-harmful coexistence), but rather a mutualistic relationship. Some human gut microorganisms benefit the host by fermentation 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 , , and . The systemic importance of the SCFAs and other compounds they produce are like hormones and the gut flora itself appears to function like an gland, and dysregulation of the gut flora has been correlated with a host of inflammatory and autoimmune conditions.
The composition of human gut microbiota changes over time, when the diet changes, and as overall health changes. A systematic review of 15 human randomized controlled trials from July 2016 found that certain commercially available strains of probiotic bacteria from the Bifidobacterium and Lactobacillus genera ( B. longum, B. breve, B. infantis, L. helveticus, L. rhamnosus, L. plantarum, and L. casei), when taken by mouth in daily doses of 109–1010 colony forming units (CFU) for 1–2 months, possess treatment efficacy (i.e., improves behavioral outcomes) in certain central nervous system disorders – including anxiety, depression, autism spectrum disorder, and obsessive–compulsive disorder – and improves certain aspects of memory.
Fungal genera that have been detected in the vagina include Candida, Pichia, Eurotium, Alternaria, Rhodotorula, and Cladosporium, among others.
Anaerobic bacteria in the oral cavity include: Actinomyces, Arachnia, Bacteroides, Bifidobacterium, Eubacterium, Fusobacterium, Lactobacillus, Leptotrichia, Peptococcus, Peptostreptococcus, Propionibacterium, Selenomonas, Treponema, and Veillonella. Genera of fungi that are frequently found in the mouth include Candida, Cladosporium, Aspergillus, Fusarium, Glomus, Alternaria, Penicillium, and Cryptococcus, among others.
Bacteria accumulate on both the hard and soft oral tissues in biofilm allowing them to adhere and strive in the oral environment while protected from the environmental factors and antimicrobial agents. Saliva plays a key biofilm homeostatic role allowing recolonization of bacteria for formation and controlling growth by detaching biofilm buildup.
Oral bacteria have evolved mechanisms to sense their environment and evade or modify the host. However, a highly efficient innate host defense system constantly monitors the bacterial colonization and prevents bacterial invasion of local tissues. A dynamic equilibrium exists between dental plaque bacteria and the innate host defense system.
This dynamic between host oral cavity and oral microbes plays a key role in health and disease as it provides entry into the body.
A healthy equilibrium presents a symbiotic relationship where oral microbes limit growth and adherence of pathogens while the host provides an environment for them to flourish. Ecological changes such as change of immune status, shift of resident microbes and nutrient availability shift from a mutual to parasitic relationship resulting in the host being prone to oral and systemic disease. Systemic diseases such as diabetes and cardiovascular diseases has been correlated to poor oral health. Of particular interest is the role of oral microorganisms in the two major dental diseases: dental caries and periodontal disease. Pathogen colonization at the periodontium cause an excessive immune response resulting in a periodontal pocket- a deepened space between the tooth and gingiva. This acts as a protected blood-rich reservoir with nutrients for anaerobic pathogens. Systemic disease at various sites of the body can result from oral microbes entering the blood bypassing periodontal pockets and oral membranes.
Persistent proper oral hygiene is the primary method for preventing oral and systemic disease. It reduces the density of biofilm and overgrowth of potential pathogenic bacteria resulting in disease. However, proper oral hygiene may not be enough as the oral microbiome, genetics, and changes to immune response play a factor in developing chronic infections. Use of antibiotics could treat already spreading infection but ineffective against bacteria within biofilms.
Unusual distributions of bacterial and fungal genera in the respiratory tract is observed in people with cystic fibrosis. Their bacterial flora often contains antibiotic-resistant and slow-growing bacteria, and the frequency of these pathogens changes in relation to age.
The microbiota may affect carcinogenesis in three broad ways: (i) altering the balance of tumor cell proliferation and death, (ii) regulating immune system function, and (iii) influencing metabolism of host-produced factors, foods and pharmaceuticals. Tumors arising at boundary surfaces, such as the skin, oropharynx and respiratory, digestive and urogenital tracts, harbor a microbiota. Substantial microbe presence at a tumor site does not establish association or causal links. Instead, microbes may find tumor oxygen tension or nutrient profile supportive. Decreased populations of specific microbes or induced oxidative stress may also increase risks. Of the around 1030 microbes on earth, ten are designated by the International Agency for Research on Cancer as human carcinogens. Microbes may secrete proteins or other factors directly drive cell proliferation in the host, or may upregulation or downregulation the host immune system including driving acute or chronic inflammation in ways that contribute to carcinogenesis.
Concerning the relationship of immune function and development of inflammation, Mucous membrane surface barriers are subject to environmental risks and must rapidly repair to maintain homeostasis. Compromised host or microbiota resiliency also reduce resistance to malignancy, possibly inducing inflammation and cancer. Once barriers are breached, microbes can elicit proinflammatory or immunosuppressive programs through various pathways. For example, cancer-associated microbes appear to activate NF-κΒ signaling within the tumor microenvironment. Other pattern recognition receptors, such as nucleotide-binding oligomerization domain–like receptor (NLR) family members NOD-2, NLRP3, NLRP6 and NLRP12, may play a role in mediating colorectal cancer. Likewise Helicobacter pylori appears to increase the risk of gastric cancer, due to its driving a chronic inflammatory response in the stomach.
Vaginal microbiota plays a role in the infectivity of HIV, with an increased risk of infection and transmission when the woman has bacterial vaginosis, a condition characterized by an abnormal balance of vaginal bacteria. The enhanced infectivity is seen with the increase in pro-inflammatory cytokines and CCR5 + CD4+ cells in the vagina. However, a decrease in infectivity is seen with increased levels of vaginal Lactobacillus, which promotes an anti-inflammatory condition.
Analysis after the processing
Marker gene analysis
Phylogenetic analysis
Ecological Network analysis
Types
Bacteria
Archaea
Fungi
Viruses
Anatomical areas
Skin
Conjunctiva
Gastrointestinal tract
Urethra and bladder
Vagina
Placenta
Uterus
Oral cavity
Nasal cavity
Lung
Biliary tract
Disease and death
Clostridioides difficile infection
Cancer
Inflammatory bowel disease
Disorders of the gut-brain interaction
/ref>
Öhman, Lena, and Magnus Simrén. "Intestinal microbiota and its role in irritable bowel syndrome (IBS)." Current gastroenterology reports 15 (2013): 1-7.
Human immunodeficiency virus
Gut microbiome of centenarians
Death
Environmental health
Changes, modulation and transmission
Person-to-person transmission
Research
Migration
Cellulose digestion
Sexome
See also
Bibliography
External links
|
|