Thehuman microbiome is the aggregate of allmicrobiota that reside on or withinhuman tissues andbiofluids along with the correspondinganatomical sites in which they reside,[1][2] including thegastrointestinal tract,skin,mammary glands,seminal fluid,uterus,ovarian follicles,lung,saliva,oral mucosa,conjunctiva, and thebiliary tract. Types ofhuman microbiota includebacteria,archaea,fungi,protists, andviruses. Thoughmicro-animals can also live on the human body, they are typically excluded from this definition. In the context ofgenomics, the termhuman microbiome is sometimes used to refer to the collectivegenomes of resident microorganisms;[3] however, the termhuman metagenome has the same meaning.[1]
The human body hosts many microorganisms, with approximately the sameorder of magnitude of non-human cells as human cells.[4] Some microorganisms that humans host arecommensal, meaning they co-exist without harming humans; others have amutualistic relationship with their human hosts.[3]: 700 [5] Conversely, some non-pathogenic microorganisms can harm human hosts via themetabolites they produce, liketrimethylamine, which the human body converts totrimethylamine N-oxide viaFMO3-mediated oxidation.[6][7] 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 deemednormal flora ornormal microbiota.[3]
During early life, the establishment of a diverse and balanced human microbiota plays a critical role in shaping an individual's long-term health.[8] 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.[9] There are several beneficial species of bacteria and potential probiotics present inbreast milk.[10] 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.[11] 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.[12]
TheHuman 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.[3] It reached a milestone in 2012 when it published its initial results.[13]
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Though widely known asflora ormicroflora, this is amisnomer in technical terms, since the word rootflora pertains to plants, andbiota refers to the total collection of organisms in a particular ecosystem. Recently, the more appropriate termmicrobiota is applied, though its use has not eclipsed the entrenched use and recognition offlora with regard to bacteria and other microorganisms. Both terms are being used in different literature.[5]
The number ofbacterial cells in thehuman body is estimated to be around 38 trillion, while the estimate forhuman cells is around 30 trillion.[14][15][16][17] The number ofbacterial genes is estimated to be 2 million, 100 times the number of approximately 20,000human genes.[18][19][20]
The problem of elucidating the human microbiome is essentially identifying the members of a microbial community, which includes bacteria, eukaryotes, and viruses.[21] This is done primarily usingdeoxyribonucleic acid (DNA)-based studies, thoughribonucleic acid (RNA), protein and metabolite based studies are also performed.[21][22] DNA-based microbiome studies typically can be categorized as either targetedamplicon studies or, more recently,shotgunmetagenomic studies. The former focuses on specific known marker genes and is primarily informative taxonomically, while the latter is an entire metagenomic approach which can also be used to study the functional potential of the community.[21] One of the challenges that is present in human microbiome studies, but not in other metagenomic studies, is to avoid including the host DNA in the study.[23]
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.[24][25] 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.[5]
On 13 June 2012, a major milestone of the HMP was announced by theNational Institutes of Health (NIH) directorFrancis Collins.[13] The announcement was accompanied with a series of coordinated articles published inNature[26][27] and several journals in thePublic 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 thegenera.[28]
The statistical analysis is essential to validate the obtained results (ANOVA can be used to size the differences between the groups); if it is paired with graphical tools, the outcome is easily visualized and understood.[29]
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 recoveredgenes 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 againstorthologs databases.[30]
It is a technique that exploitsprimers to target a specific genetic region and enables to determine the microbialphylogenies. The genetic region is characterized by a highly variable region which can confer detailed identification; it is delimited by conserved regions, which function asbinding sites for primers used inPCR. The main gene used to characterizebacteria andarchaea is16SrRNA gene, while fungi identification is based onInternal Transcribed Spacer (ITS). The technique is fast and not so expensive and enables to obtain a low-resolution classification of a microbial sample; it is optimal for samples that may be contaminated by host DNA. Primer affinity varies among all DNA sequences, which may result in biases during the amplification reaction; indeed, low-abundance samples are susceptible to overamplification errors, since the other contaminating microorganisms result to be over-represented in case of increasing the PCR cycles. Therefore, the optimization of primer selection can help to decrease such errors, although it requires complete knowledge of the microorganisms present in the sample, and their relative abundances.[31]
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 intoOperational 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 discardSNPs because they would get clustered into a single OTU. Another approach isOligotyping, 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.[31]
Another important step in the analysis is to assign a taxonomic name to microbial sequences in the data. This can be done usingmachine 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.[31]
Many methods that exploit phylogenetic inference use the16SRNA gene for Archea and Bacteria and the18SRNA gene for Eukaryotes.Phylogenetic comparative methods (PCS) are based on the comparison of multiple traits among microorganisms; the principle is: the closely they are related, the higher number of traits they share. Usually PCS are coupled with phylogenetic generalized least square (PGLS) or other statistical analysis to get more significant results. Ancestral state reconstruction is used in microbiome studies to impute trait values for taxa whose traits are unknown. This is commonly performed withPICRUSt, which relies on available databases.Phylogenetic variables are chosen by researchers according to the type of study: through the selection of some variables with significant biological informations, it is possible to reduce the dimension of the data to analyse.[32]
Phylogenetic aware distance is usually performed withUniFrac 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 byhorizontal 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.[32]
Microbial communities develop in a very complex dynamic which can be viewed and analyzed as an ecosystem. The ecological interactions between microbes govern its change, equilibrium and stability, and can be represented by a population dynamic model.[33]The ongoing study of ecological features of the microbiome is growing rapidly and allows to understand the fundamental properties of the microbiome. Understanding the underlying rules of microbial community could help with treating diseases related to unstable microbial communities.A very basic question is if different humans, who share different microbial communities, have the same underlying microbial dynamics.[34] Increasing evidence and indications have found that the dynamics is indeed universal.[35] This question is a basic step that will allow scientists to develop treatment strategies, based on the complex dynamics of human microbial communities.There are more important properties on which considerations should be taken into account for developing interventions strategies for controlling the human microbial dynamics.[36] Controlling the microbial communities could result in solving very bad and harmful diseases.
Populations of microbes (such asbacteria andyeasts) inhabit the skin and mucosal surfaces in various parts of the body. Their role forms part of normal, healthy human physiology, however if microbe numbers grow beyond their typical ranges (often due to a compromised immune system) or if microbes populate (such as through poor hygiene or injury) areas of the body normally not colonized or sterile (such as the blood, or the lower respiratory tract, or the abdominal cavity), disease can result (causing, respectively, bacteremia/sepsis, pneumonia, and peritonitis).[37]
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.[38][39]
It is estimated that 500 to 1,000species of bacteria live in the human gut but belong to just a few phyla:Bacillota andBacteroidota dominate but there are alsoPseudomonadota,Verrucomicrobiota,Actinobacteriota,Fusobacteriota, and "Cyanobacteria".[40]
A number of types of bacteria, such asActinomyces viscosus andA. naeslundii, live in the mouth, where they are part of a sticky substance calledplaque. If this is not removed by brushing, it hardens intocalculus (also called tartar). The same bacteria also secrete acids that dissolvetooth enamel, causingtooth decay.[citation needed]
Thevaginal microflora consist mostly of variouslactobacillus species. It was long thought that the most common of these species wasLactobacillus acidophilus, but it has later been shown thatL. iners is in fact most common, followed byL. crispatus. Other lactobacilli found in the vagina areL. jensenii,L. delbruekii andL. gasseri. Disturbance of the vaginal flora can lead to infections such asbacterial vaginosis andcandidiasis.[41]
Archaea are present in the human gut, but, in contrast to the enormous variety ofbacteria in this organ, the numbers of archaeal species are much more limited.[42] The dominant group are themethanogens, particularlyMethanobrevibacter smithii andMethanosphaera stadtmanae.[43] However, colonization by methanogens is variable, and only about 50% of humans have easily detectable populations of these organisms.[44]
As of 2007, no clear examples of archaealpathogens were known,[45][46] although a relationship has been proposed between the presence of some methanogens and humanperiodontal disease.[47]Methane-dominant small intestinal bacterial overgrowth (SIBO) is also predominantly caused by methanogens, andMethanobrevibacter smithii in particular.[48]
Fungi, in particularyeasts, are present in the human gut.[49][50][51][52] The best-studied of these areCandida species due to their ability to become pathogenic inimmunocompromised and even in healthy hosts.[50][51][52] Yeasts are also present on the skin,[49] such asMalassezia species, where they consume oils secreted from thesebaceous glands.[53][54]
Viruses, especially bacterial viruses (bacteriophages), colonize various body sites. These colonized sites include the skin,[55] gut,[56] lungs,[57] and oral cavity.[58] Virus communities have been associated with some diseases, and do not simply reflect the bacterial communities.[59][60][61]
In January 2024, biologists reported the discovery of "obelisks", a new class ofviroid-like elements, and "oblins", their related group of proteins, in the human microbiome.[62][63]
A study of 20 skin sites on each of ten healthy humans found 205 identified genera in 19 bacterial phyla, with most sequences assigned to four phyla:Actinomycetota (51.8%),Bacillota (24.4%),Pseudomonadota (16.5%), andBacteroidota (6.3%).[64] A large number of fungal genera are present on healthy human skin, with some variability by region of the body; however, during pathological conditions, certain genera tend to dominate in the affected region.[49] For example,Malassezia is dominant inatopic dermatitis andAcremonium is dominant on dandruff-affected scalps.[49]
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.[3]
A small number of bacteria and fungi are normally present in theconjunctiva.[49][65] Classes of bacteria include Gram-positive cocci (e.g.,Staphylococcus andStreptococcus) and Gram-negative rods and cocci (e.g.,Haemophilus andNeisseria) are present.[65] Fungal genera includeCandida,Aspergillus, andPenicillium.[49] Thelachrymal glands continuously secrete, keeping the conjunctiva moist, while intermittent blinking lubricates the conjunctiva and washes away foreign material. Tears contain bactericides such aslysozyme, so that microorganisms have difficulty in surviving the lysozyme and settling on theepithelial surfaces.
 Tryptophanase- expressing bacteria Intestinal immune cells Neuroprotectant: ↓Activation ofglial cells andastrocytes ↓4-Hydroxy-2-nonenal levels ↓DNA damage –Antioxidant –Inhibitsβ-amyloid fibril formation Maintains mucosal reactivity: ↑IL-22 production Associated withvascular disease: ↑Oxidative stress ↑Smooth muscle cellproliferation ↑Aortic wall thickness andcalcification Associated withchronic kidney disease: ↑Renal dysfunction –Uremic toxin  |
In humans, the composition of the gastrointestinal microbiome is established during birth.[70] Birth byCesarean section or vaginal delivery also influences the gut's microbial composition. Babies born through the vaginal canal have non-pathogenic, beneficial gut microbiota similar to those found in the mother.[71] However, the gut microbiota of babies delivered by C-section harbors more pathogenic bacteria such asEscherichia coli andStaphylococcus and it takes longer to develop non-pathogenic, beneficial gut microbiota.[72]
The relationship between somegut microbiota and humans is not merelycommensal (a non-harmful coexistence), but rather amutualistic relationship.[3] Some human gut microorganisms benefit the host byfermentingdietary fiber intoshort-chain fatty acids (SCFAs), such asacetic acid andbutyric acid, which are then absorbed by the host.[5][73] Intestinalbacteria also play a role in synthesizingvitamin B andvitamin K as well as metabolizingbile acids,sterols, andxenobiotics.[3][73] The systemic importance of the SCFAs and other compounds they produce are likehormones and the gut flora itself appears to function like anendocrine organ,[73] and dysregulation of the gut flora has been correlated with a host of inflammatory and autoimmune conditions.[5][74]
The composition of human gut microbiota changes over time, when the diet changes, and as overall health changes.[5][74] Asystematic review of 15 humanrandomized controlled trials from July 2016 found that certain commercially available strains of probiotic bacteria from theBifidobacterium andLactobacillusgenera (B. longum,B. breve,B. infantis,L. helveticus,L. rhamnosus,L. plantarum, andL. casei), whentaken 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 certaincentral nervous system disorders – includinganxiety,depression,autism spectrum disorder, andobsessive–compulsive disorder – and improves certain aspects ofmemory.[75]
Thegenitourinary system appears to have a microbiota,[76][77] which is an unexpected finding in light of the long-standing use of standard clinicalmicrobiological culture methods to detectbacteria in urine when people show signs of aurinary tract infection; it is common for these tests to show no bacteria present.[78] It appears that commonculture methods do not detect many kinds of bacteria and othermicroorganisms that are normally present.[78] As of 2017,sequencing methods were used to identify these microorganisms to determine if there are differences in microbiota between people with urinary tract problems and those who are healthy.[76][77][79] To properly assess the microbiome of the bladder as opposed to the genitourinary system, the urine specimen should be collected directly from the bladder, which is often done with acatheter.[80]
Vaginal microbiota refers to those species and genera that colonize the vagina. These organisms play an important role in protecting against infections and maintaining vaginal health.[81] The most abundant vaginal microorganisms found in premenopausal women are from the genusLactobacillus, which suppress pathogens by producinghydrogen peroxide and lactic acid.[51][81][82] Bacterialspecies composition and ratios vary depending on the stage of themenstrual cycle.[83][84][needs update] Ethnicity also influences vaginal flora. The occurrence of hydrogen peroxide-producing lactobacilli is lower in African American women and vaginal pH is higher.[85] Other influential factors such as sexual intercourse and antibiotics have been linked to the loss of lactobacilli.[82] Moreover, studies have found that sexual intercourse with a condom does appear to change lactobacilli levels, and does increase the level ofEscherichia coli within the vaginal flora.[82] Changes in the normal, healthy vaginal microbiota is an indication of infections,[86] such ascandidiasis orbacterial vaginosis.[82]Candida albicans inhibits the growth ofLactobacillus species, whileLactobacillus species which produce hydrogen peroxide inhibit the growth and virulence ofCandida albicans in both the vagina and the gut.[49][51][52]
Fungal genera that have been detected in the vagina includeCandida,Pichia,Eurotium,Alternaria,Rhodotorula, andCladosporium, among others.[49]
Until recently theplacenta was considered to be a sterile organ but commensal, nonpathogenic bacterial species and genera have been identified that reside in the placental tissue.[87][88][89] However, the existence of a microbiome in the placenta is controversial as criticized in several researches. So called "placental microbiome" is likely derived from contamination of regents because low-biomass samples are easily contaminated.[90][91][92]
Until recently, the upper reproductive tract of women was considered to be a sterile environment. A variety of microorganisms inhabit the uterus of healthy, asymptomatic women of reproductive age. The microbiome of the uterus differs significantly from that of the vagina and gastrointestinal tract.[93]
The environment present in the human mouth allows the growth of characteristic microorganisms found there. It provides a source of water and nutrients, as well as a moderate temperature.[3] Resident microbes of the mouth adhere to the teeth and gums to resist mechanical flushing from the mouth to stomach where acid-sensitive microbes are destroyed byhydrochloric acid.[3][51]
Anaerobic bacteria in the oral cavity include:Actinomyces,Arachnia,Bacteroides,Bifidobacterium,Eubacterium,Fusobacterium,Lactobacillus,Leptotrichia,Peptococcus,Peptostreptococcus,Propionibacterium,Selenomonas,Treponema, andVeillonella.[94][needs update] Genera of fungi that are frequently found in the mouth includeCandida,Cladosporium,Aspergillus,Fusarium,Glomus,Alternaria,Penicillium, andCryptococcus, among others.[49]
Bacteria accumulate on both the hard and soft oral tissues inbiofilm allowing them to adhere and strive in the oral environment while protected from the environmental factors and antimicrobial agents.[95] Saliva plays a key biofilm homeostatic role allowing recolonization of bacteria for formation and controlling growth by detaching biofilm buildup.[96] It also provides a means of nutrients and temperature regulation. The location of the biofilm determines the type of exposed nutrients it receives.[97]
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 betweendental plaque bacteria and the innate host defense system.[98]
This dynamic between host oral cavity and oral microbes plays a key role in health and disease as it provides entry into the body.[99]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.[99][95] 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.[95] Systemic diseases such as diabetes and cardiovascular diseases has been correlated to poor oral health.[99] Of particular interest is the role of oral microorganisms in the two major dental diseases:dental caries andperiodontal disease.[98] Pathogen colonization at the periodontium cause an excessive immune response resulting in a periodontal pocket- a deepened space between the tooth and gingiva.[95] This acts as a protected blood-rich reservoir with nutrients for anaerobic pathogens.[95] Systemic disease at various sites of the body can result from oral microbes entering the blood bypassing periodontal pockets and oral membranes.[99]
Persistent proper oral hygiene is the primary method for preventing oral and systemic disease.[99] It reduces the density of biofilm and overgrowth of potential pathogenic bacteria resulting in disease.[97] 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.[97] Use of antibiotics could treat already spreading infection but ineffective against bacteria within biofilms.[97]
The healthy nasal microbiome is dominated byCorynebacterium andStaphylococcus species. The mucosal microbiome plays a critical role in modulating viral infection.[100]
Much like the oral cavity, the upper and lower respiratory system possess mechanical deterrents to remove microbes. Goblet cells produce mucus which traps microbes and moves them out of the respiratory system via continuously movingciliated epithelial cells.[3] In addition, a bactericidal effect is generated by nasal mucus which contains the enzyme lysozyme.[3] The upper and lower respiratory tract appears to have its own set of microbiota.[101] Pulmonary bacterial microbiota belong to 9 major bacterial genera:Prevotella,Sphingomonas,Pseudomonas,Acinetobacter,Fusobacterium,Megasphaera,Veillonella,Staphylococcus, andStreptococcus. Some of the bacteria considered "normal biota" in the respiratory tract can cause serious disease especially in immunocompromised individuals; these includeStreptococcus pyogenes,Haemophilus influenzae,Streptococcus pneumoniae,Neisseria meningitidis, andStaphylococcus aureus.[citation needed] Fungal genera that compose the pulmonary mycobiome includeCandida,Malassezia,Neosartorya,Saccharomyces, andAspergillus, among others.[49]
Unusual distributions of bacterial and fungal genera in the respiratory tract is observed in people withcystic fibrosis.[49][102] Their bacterial flora often contains antibiotic-resistant and slow-growing bacteria, and the frequency of these pathogens changes in relation to age.[102]
Traditionally the biliary tract has been considered to be normally sterile, and the presence of microorganisms in bile is a marker of pathological process. This assumption was confirmed by failure in allocation of bacterial strains from the normal bile duct. Papers began emerging in 2013 showing that the normal biliary microbiota is a separate functional layer which protects a biliary tract from colonization by exogenous microorganisms.[103]
Human bodies rely on the innumerable bacterial genes as the source of essential nutrients.[104] Both metagenomic and epidemiological studies indicate vital roles for the human microbiome in preventing a wide range of diseases, from type 2 diabetes and obesity to inflammatory bowel disease, Parkinson's disease, and even mental health conditions like depression.[105] A symbiotic relationship between thegut microbiota and different bacteria may influence an individual's immune response.[106] Metabolites generated by gut microbes appear to be causative factors in type 2 diabetes.[107] Although in its infancy, microbiome-based treatment is also showing promise, most notably for treating drug-resistantC. difficileArchived 7 December 2019 at theWayback Machine infection[108] and in diabetes treatment.[109]
An overwhelming presence of the bacteria,C. difficile, leads to an infection of the gastrointestinal tract, normally associated to dysbiosis with the microbiota believed to have been caused by the administration of antibiotics. Use of antibiotics eradicates the beneficial gut flora within the gastrointestinal tract, which normally prevents pathogenic bacteria from establishing dominance.[110] Traditional treatment forC. difficile infections includes an additional regime of antibiotics, however, efficacy rates average between 20 and 30%.[111] Recognizing the importance of healthy gut bacteria, researchers turned to a procedure known asfecal microbiota transplant (FMT), where patients experiencing gastrointestinal diseases, such asC. difficile infection (CDI), receive fecal content from a healthy individual in hopes of restoring a normal functioning intestinal microbiota.[112] Fecal microbiota transplant is approximately 85–90% effective in people with CDI for whom antibiotics have not worked or in whom the disease recurs following antibiotics.[113][114] Most people with CDI recover with one FMT treatment.[115][110][116]
Although cancer is generally a disease of host genetics and environmental factors, microorganisms are implicated in some 20% of human cancers.[117] Particularly for potential factors incolon cancer, bacterial density is one million times higher than in thesmall intestine, and approximately 12-fold more cancers occur in the colon compared to the small intestine, possibly establishing a pathogenic role for microbiota in colon andrectal cancers.[118] Microbial density may be used as aprognostic tool in assessment of colorectal cancers.[118]
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.[117] Tumors arising at boundary surfaces, such as the skin,oropharynx and respiratory, digestive andurogenital tracts, harbor a microbiota. Substantial microbe presence at a tumor site does not establish association or causal links. Instead, microbes may find tumoroxygen tension or nutrient profile supportive. Decreased populations of specific microbes or inducedoxidative stress may also increase risks.[117][118] Of the around 1030 microbes on earth, ten are designated by theInternational Agency for Research on Cancer as human carcinogens.[117] Microbes may secrete proteins or other factors directly drive cell proliferation in the host, or mayup- ordown-regulate the host immune system including driving acute or chronic inflammation in ways that contribute to carcinogenesis.[117]
Concerning the relationship of immune function and development of inflammation,mucosal surface barriers are subject to environmental risks and must rapidly repair to maintainhomeostasis. 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.[117] For example, cancer-associated microbes appear to activate NF-κΒ signaling within the tumor microenvironment. Other pattern recognition receptors, such asnucleotide-binding oligomerization domain–like receptor (NLR) family membersNOD-2,NLRP3,NLRP6 andNLRP12, may play a role in mediating colorectal cancer.[117] LikewiseHelicobacter pylori appears to increase the risk of gastric cancer, due to its driving a chronic inflammatory response in the stomach.[117][118]
Inflammatory bowel disease consists of two different diseases: ulcerative colitis and Crohn's disease and both of these diseases present with disruptions in the gut microbiota (also known asdysbiosis). This dysbiosis presents itself in the form of decreased microbial diversity in the gut,[119][120] and is correlated to defects in host genes that changes the innate immune response in individuals.[119]
TheHIV disease progression influences the composition and function of the gut microbiota, with notable differences between HIV-negative, HIV-positive, and post-ART HIV-positive populations.[citation needed] HIV decreases the integrity of the gut epithelial barrier function by affectingtight junctions. This breakdown allows for translocation across the gut epithelium, which is thought to contribute to increases in inflammation seen in people with HIV.[121]
Vaginal microbiota plays a role in the infectivity of HIV, with an increased risk of infection and transmission when the woman hasbacterial vaginosis, a condition characterized by an abnormal balance of vaginal bacteria.[122] The enhanced infectivity is seen with the increase inpro-inflammatory cytokines andCCR5 + CD4+ cells in the vagina. However, a decrease in infectivity is seen with increased levels of vaginalLactobacillus, which promotes an anti-inflammatory condition.[121]
Humans who are 100 years old or older, calledcentenarians, have a distinct gut microbiome. This microbiome is characteristically enriched inmicroorganisms that are able to synthesize novel secondarybile acids.[123] These secondary bile acids include various isoforms oflithocholic acid that may contribute to healthy aging.[123]
With death, the microbiome of the living body collapses and a different composition of microorganisms namednecrobiome establishes itself as an important active constituent of the complex physical decomposition process. Its predictable changes over time are thought to be useful to help determine the time of death.[124][125]
Studies in 2009 questioned whether the decline inbiota (includingmicrofauna) as a result of human intervention might impede human health, hospital safety procedures, food product design, and treatments of disease.[126]
Hygiene,[128]probiotics,[127]prebiotics,[129]synbiotics,[130]light therapy,[131] microbiota transplants (fecal[132] orskin[133]),antibiotics,[134]exercise,[135][136]diet,[137]breastfeeding,[138]aging[139] can change the human microbiome across various anatomical systems or regions such as skin and gut.
The human microbiome is transmitted between amother and herchildren, as well as between people living in the samehousehold.[140][141]
Primary research indicates that immediate changes in the microbiota may occur when a personmigrates from one country to another, such as whenThaiimmigrants settled in the United States[142] or whenLatin Americans immigrated into the United States.[143] Losses of microbiota diversity were greater inobese individuals andchildren of immigrants.[142][143]
A 2024 study suggests thatgut microbiota capable ofdigestingcellulose can be found in the human microbiome, and they are less abundant in people living inindustrialized societies.[144][145]
The sexome refers to microbes left on genitalia after penetrative sex. In the context offorensic science, the sexome can potentially aid in sexual assault casework for perpetrator identification when human male DNA is absent.[146]
Microbiome
This term refers to the entire habitat, including the microorganisms (bacteria, archaea, lower and higher eurkaryotes, and viruses), their genomes (i.e., genes), and the surrounding environmental conditions. This definition is based on that of "biome," the biotic and abiotic factors of given environments. Others in the field limit the definition of microbiome to the collection of genes and genomes of members of a microbiota. It is argued that this is the definition ofmetagenome, which combined with the environment constitutes the microbiome.
we review literature on trimethylamine (TMA), a microbiota-generated metabolite linked to atherosclerosis development.
Trimethylamine is exclusively a microbiota-derived product of nutrients (lecithin, choline, TMAO, L-carnitine) from normal diet, from which seems originate two diseases, trimethylaminuria (or Fish-Odor Syndrome) and cardiovascular disease through the proatherogenic property of its oxidized liver-derived form.
Candida species and other microorganisms are involved in this complicated fungal infection, butCandida albicans continues to be the most prevalent. In the past two decades, it has been observed an abnormal overgrowth in the gastrointestinal, urinary and respiratory tracts, not only in immunocompromised patients, but also related to nosocomial infections and even in healthy individuals. There is a widely variety of causal factors that contribute to yeast infection which means that candidiasis is a good example of a multifactorial syndrome.
In addition, GI fungal infection is reported even among those patients with normal immune status. Digestive system-related fungal infections may be induced by both commensal opportunistic fungi and exogenous pathogenic fungi. ...Candida sp. is also the most frequently identified species among patients with gastric IFI. ... It was once believed that gastric acid could kill microbes entering the stomach and that the unique ecological environment of the stomach was not suitable for microbial colonisation or infection. However, several studies using culture-independent methods confirmed that large numbers of acid-resistant bacteria belonging to eight phyla and up to 120 species exist in the stomach, such asStreptococcus sp.,Neisseria sp. andLactobacillus sp. etc.26, 27 Furthermore,Candida albicans can grow well in highly acidic environments,28 and some genotypes may increase the severity of gastric mucosal lesions.29
Small intestinal fungal overgrowth (SIFO) is characterized by the presence of excessive number of fungal organisms in the small intestine associated with gastrointestinal (GI) symptoms. Candidiasis is known to cause GI symptoms particularly in immunocompromised patients or those receiving steroids or antibiotics. However, only recently, there is emerging literature that an overgrowth of fungus in the small intestine of non-immunocompromised subjects may cause unexplained GI symptoms. Two recent studies showed that 26 % (24/94) and 25.3 % (38/150) of a series of patients with unexplained GI symptoms had SIFO. The most common symptoms observed in these patients were belching, bloating, indigestion, nausea, diarrhea, and gas. ... Fungal-bacterial interaction may act in different ways and may either be synergistic or antagonistic or symbiotic [29]. Some bacteria such asLactobacillus species can interact and inhibit both the virulence and growth ofCandida species in the gut by producing hydrogen peroxide [30]. Any damage to the mucosal barrier or disruption of GI microbiota with chemotherapy or antibiotic use, inflammatory processes, activation of immune molecules and disruption of epithelial repair may all cause fungal overgrowth [27].
Lactobacillus spp. convert tryptophan to indole-3-aldehyde (I3A) through unidentified enzymes [125].Clostridium sporogenes convert tryptophan to IPA [6], likely via a tryptophan deaminase. ... IPA also potently scavenges hydroxyl radicals
Production of IPA was shown to be completely dependent on the presence of gut microflora and could be established by colonization with the bacteriumClostridium sporogenes.
[Indole-3-propionic acid (IPA)] has previously been identified in the plasma and cerebrospinal fluid of humans, but its functions are not known. ... In kinetic competition experiments using free radical-trapping agents, the capacity of IPA to scavenge hydroxyl radicals exceeded that of melatonin, an indoleamine considered to be the most potent naturally occurring scavenger of free radicals. In contrast with other antioxidants, IPA was not converted to reactive intermediates with pro-oxidant activity.
These probiotics showed efficacy in improving psychiatric disorder-related behaviors including anxiety, depression, autism spectrum disorder (ASD), obsessive-compulsive disorder, and memory abilities, including spatial and non-spatial memory. Because many of the basic science studies showed some efficacy of probiotics on central nervous system function, this background may guide and promote further preclinical and clinical studies. ... According to the qualitative analyses of current studies, we can provisionally draw the conclusion that B. longum, B. breve, B. infantis, L. helveticus, L. rhamnosus, L. plantarum, and L. casei were most effective in improving CNS function, including psychiatric disease-associated functions (anxiety, depression, mood, stress response) and memory abilities
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