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Microbiota

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,[2][3] and have been found to be crucial for immunologic, hormonal, and metabolic homeostasis of their host.

Diverse microbial communities of characteristic microbiota are part of plant microbiomes, and are found on the outside surfaces and in the internal tissues of the host plant, as well as in the surrounding soil.[1]

The term microbiome describes either the collective genomes of the microbes that reside in an ecological niche or else the microbes themselves.[4][5][6]

The microbiome and host emerged during evolution as a synergistic unit from epigenetics and genetic characteristics, sometimes collectively referred to as a holobiont.[7][8] The presence of microbiota in human and other metazoan guts has been critical for understanding the co-evolution between metazoans and bacteria.[9][10] Microbiota play key roles in the intestinal immune and metabolic responses via their fermentation product (short-chain fatty acid), acetate.[11]

Introduction edit

 
The predominant species of bacteria on human skin

All plants and animals, from simple life forms to humans, live in close association with microbial organisms.[12] Several advances have driven the perception of microbiomes, including:

  • the ability to perform genomic and gene expression analyses of single cells and of entire microbial communities in the disciplines of metagenomics and metatranscriptomics[13]
  • databases accessible to researchers across multiple disciplines[13]
  • methods of mathematical analysis suitable for complex data sets[13]

Biologists have come to appreciate that microbes make up an important part of an organism's phenotype, far beyond the occasional symbiotic case study.[13]

Types of microbe-host relationships edit

Commensalism, a concept developed by Pierre-Joseph van Beneden (1809–1894), a Belgian professor at the University of Louvain during the nineteenth century [14] is central to the microbiome, where microbiota colonize a host in a non-harmful coexistence. The relationship with their host is called mutualistic when organisms perform tasks that are known to be useful for the host,[15]: 700 [16] parasitic, when disadvantageous to the host. Other authors define a situation as mutualistic where both benefit, and commensal, where the unaffected host benefits the symbiont.[17] A nutrient exchange may be bidirectional or unidirectional, may be context dependent and may occur in diverse ways.[17] Microbiota that are expected to be present, and that under normal circumstances do not cause disease, are deemed normal flora or normal microbiota;[15] normal flora can not only be harmless, but can be protective of the host.[18]

Acquisition and change edit

The initial acquisition of microbiota in animals from mammalians to marine sponges is at birth, and may even occur through the germ cell line. In plants, the colonizing process can be initiated below ground in the root zone, around the germinating seed, the spermosphere, or originate from the above ground parts, the phyllosphere and the flower zone or anthosphere.[19] The stability of the rhizosphere microbiota over generations depends upon the plant type but even more on the soil composition, i.e. living and non living environment.[20] Clinically, new microbiota can be acquired through fecal microbiota transplant to treat infections such as chronic C. difficile infection.[21]

Microbiota by host edit

 
Pathogenic microbiota causing inflammation in the lung

Humans edit

The human microbiota includes bacteria, fungi, archaea and viruses. Micro-animals which live on the human body are excluded. The human microbiome refers to their collective genomes.[15]

Humans are colonized by many microorganisms; the traditional estimate was that humans live with ten times more non-human cells than human cells; more recent estimates have lowered this to 3:1 and even to about 1:1.[22][23][24][25]

In fact, these are so small that there are around 100 trillion microbiota on the human body.[26]

The Human Microbiome Project sequenced the genome of the human microbiota, focusing particularly on the microbiota that normally inhabit the skin, mouth, nose, digestive tract, and vagina.[15] It reached a milestone in 2012 when it published initial results.[27]

Non-human animals edit

  • Amphibians have microbiota on their skin.[28] Some species are able to carry a fungus named Batrachochytrium dendrobatidis, which in others can cause a deadly infection Chytridiomycosis depending on their microbiome, resisting pathogen colonization or inhibiting their growth with antimicrobial skin peptides.[29]
  • Newborn marsupials are born with histologically immature immune tissues and unable to mount their own specific immune defence. They are therefore heavily reliant on their mother's immune system [30] and the milk [31] for their protection. Most marsupials have pouches, and their own microbiota changes throughout the reproductive stages: oestrus, birth/oestrus, and post-oestrus.[32] Some pouch and skin secretions have had antimicrobial peptides identified, that presumably support the young at this vulnerable time.
  • In mammals, herbivores such as cattle depend on their rumen microbiome to convert cellulose into proteins, short chain fatty acids, and gases. Culture methods cannot provide information on all microorganisms present. Comparative metagenomic studies yielded the surprising result that individual cattle possess markedly different community structures, predicted phenotype, and metabolic potentials,[33] even though they were fed identical diets, were housed together, and were apparently functionally identical in their utilization of plant cell wall resources.
  • Mice have become the most studied mammalian regarding their microbiomes. The gut microbiota have been studied in relation to allergic airway disease, obesity, gastrointestinal diseases and diabetes. Perinatal shifting of microbiota through low dose antibiotics can have long-lasting effects on future susceptibility to allergic airway disease. The frequency of certain subsets of microbes has been linked to disease severity. The presence of specific microbes early in postnatal life, instruct future immune responses.[34][35] In gnotobiotic mice certain gut bacteria were found to transmit a particular phenotype to recipient germ-free mice, that promoted accumulation of colonic regulatory T cells, and strains that modulated mouse adiposity and cecal metabolite concentrations.[36] This combinatorial approach enables a systems-level understanding of microbial contributions to human biology.[37] But also other mucoide tissues as lung and vagina have been studied in relation to diseases such as asthma, allergy and vaginosis.[38]
  • Insects have their own microbiomes. For example, leaf-cutter ants form huge underground colonies harvesting hundreds of kilograms of leaves each year and are unable to digest the cellulose in the leaves directly. They maintain fungus gardens as the colony's primary food source. While the fungus itself does not digest cellulose, a microbial community containing a diversity of bacteria is doing so. Analysis of the microbial population's genome revealed many genes with a role in cellulose digestion. This microbiome's predicted carbohydrate-degrading enzyme profile is similar to that of the bovine rumen, but the species composition is almost entirely different.[39] Gut microbiota of the fruit fly can affect the way its gut looks, by impacting epithelial renewal rate, cellular spacing, and the composition of different cell types in the epithelium.[40] When the moth Spodoptera exigua is infected with baculovirus immune-related genes are downregulated and the amount of its gut microbiota increases.[41] In the dipteran intestine, enteroendocrine cells sense the gut microbiota-derived metabolites and coordinate antibacterial, mechanical, and metabolic branches of the host intestinal innate immune response to the commensal microbiota.[42]
  • Fish have their own microbiomes, including the short-lived species Nothobranchius furzeri (turquoise killifish). Transferring the gut microbiota from young killfish into middle-aged killifish significantly extends the lifespans of the middle-aged killfish.[43]

Plants edit

 
Routes of colonization of potato tubers by bacteria[44]

The plant microbiome was recently discovered to originate from the seed.[45] Microorganism which are transmitted via seed migrate into the developing seedling in a specific route in which certain community move to the leaves and others to the roots.[45] In the diagram on the right, microbiota colonizing the rhizosphere, entering the roots and colonizing the next tuber generation via the stolons, are visualized with a red color. Bacteria present in the mother tuber, passing through the stolons and migrating into the plant as well as into the next generation of tubers are shown in blue.[44]

  • The soil is the main reservoir for bacteria that colonize potato tubers
  • Bacteria are recruited from the soil more or less independent of the potato variety
  • Bacteria might colonize the tubers predominantly from the inside of plants via the stolon
  • The bacterial microbiota of potato tubers consists of bacteria transmitted from one tuber generation to the next and bacteria recruited from the soil colonize potato plants via the root.[44]
 
Light micrograph of a cross section of a coralloid root of a cycad, showing the layer that hosts symbiotic cyanobacteria

Plants are attractive hosts for microorganisms since they provide a variety of nutrients. Microorganisms on plants can be epiphytes (found on the plants) or endophytes (found inside plant tissue).[46][47] Oomycetes and fungi have, through convergent evolution, developed similar morphology and occupy similar ecological niches. They develop hyphae, threadlike structures that penetrate the host cell. In mutualistic situations the plant often exchanges hexose sugars for inorganic phosphate from the fungal symbiont. It is speculated that such very ancient associations have aided plants when they first colonized land.[17][48] Plant-growth promoting bacteria (PGPB) provide the plant with essential services such as nitrogen fixation, solubilization of minerals such as phosphorus, synthesis of plant hormones, direct enhancement of mineral uptake, and protection from pathogens.[49][50] PGPBs may protect plants from pathogens by competing with the pathogen for an ecological niche or a substrate, producing inhibitory allelochemicals, or inducing systemic resistance in host plants to the pathogen[19]

Research edit

The symbiotic relationship between a host and its microbiota is under laboratory research for how it may shape the immune system of mammals.[51][52] In many animals, the immune system and microbiota may engage in "cross-talk" by exchanging chemical signals, which may enable the microbiota to influence immune reactivity and targeting.[53] Bacteria can be transferred from mother to child through direct contact and after birth.[54] As the infant microbiome is established, commensal bacteria quickly populate the gut, prompting a range of immune responses and "programming" the immune system with long-lasting effects.[53] The bacteria are able to stimulate lymphoid tissue associated with the gut mucosa, which enables the tissue to produce antibodies for pathogens that may enter the gut.[53]

The human microbiome may play a role in the activation of toll-like receptors in the intestines, a type of pattern recognition receptor host cells use to recognize dangers and repair damage. Pathogens can influence this coexistence leading to immune dysregulation including and susceptibility to diseases, mechanisms of inflammation, immune tolerance, and autoimmune diseases.[55][56]

Co-evolution of microbiota edit

 
Bleached branching coral (foreground) and normal branching coral (background). Keppel Islands, Great Barrier Reef.

Organisms evolve within ecosystems so that the change of one organism affects the change of others. The hologenome theory of evolution proposes that an object of natural selection is not the individual organism, but the organism together with its associated organisms, including its microbial communities.

Coral reefs. The hologenome theory originated in studies on coral reefs.[57] Coral reefs are the largest structures created by living organisms, and contain abundant and highly complex microbial communities. Over the past several decades, major declines in coral populations have occurred. Climate change, water pollution and over-fishing are three stress factors that have been described as leading to disease susceptibility. Over twenty different coral diseases have been described, but of these, only a handful have had their causative agents isolated and characterized. Coral bleaching is the most serious of these diseases. In the Mediterranean Sea, the bleaching of Oculina patagonica was first described in 1994 and shortly determined to be due to infection by Vibrio shiloi. From 1994 to 2002, bacterial bleaching of O. patagonica occurred every summer in the eastern Mediterranean. Surprisingly, however, after 2003, O. patagonica in the eastern Mediterranean has been resistant to V. shiloi infection, although other diseases still cause bleaching. The surprise stems from the knowledge that corals are long lived, with lifespans on the order of decades,[58] and do not have adaptive immune systems.[citation needed] Their innate immune systems do not produce antibodies, and they should seemingly not be able to respond to new challenges except over evolutionary time scales.[citation needed]

The puzzle of how corals managed to acquire resistance to a specific pathogen led to a 2007 proposal, that a dynamic relationship exists between corals and their symbiotic microbial communities. It is thought that by altering its composition, the holobiont can adapt to changing environmental conditions far more rapidly than by genetic mutation and selection alone. Extrapolating this hypothesis to other organisms, including higher plants and animals, led to the proposal of the hologenome theory of evolution.[57]

As of 2007 the hologenome theory was still being debated.[59] A major criticism has been the claim that V. shiloi was misidentified as the causative agent of coral bleaching, and that its presence in bleached O. patagonica was simply that of opportunistic colonization.[60] If this is true, the basic observation leading to the theory would be invalid. The theory has gained significant popularity as a way of explaining rapid changes in adaptation that cannot otherwise be explained by traditional mechanisms of natural selection. Within the hologenome theory, the holobiont has not only become the principal unit of natural selection but also the result of other step of integration that it is also observed at the cell (symbiogenesis, endosymbiosis) and genomic levels.[7]

Research methods edit

Targeted amplicon sequencing edit

Targeted amplicon sequencing relies on having some expectations about the composition of the community that is being studied. In target amplicon sequencing a phylogenetically informative marker is targeted for sequencing. Such a marker should be present in ideally all the expected organisms. It should also evolve in such a way that it is conserved enough that primers can target genes from a wide range of organisms while evolving quickly enough to allow for finer resolution at the taxonomic level. A common marker for human microbiome studies is the gene for bacterial 16S rRNA (i.e. "16S rDNA", the sequence of DNA which encodes the ribosomal RNA molecule).[61] Since ribosomes are present in all living organisms, using 16S rDNA allows for DNA to be amplified from many more organisms than if another marker were used. The 16S rRNA gene contains both slowly evolving regions and 9 fast evolving regions, also known as hypervariable regions (HVRs);[62] the former can be used to design broad primers while the latter allow for finer taxonomic distinction. However, species-level resolution is not typically possible using the 16S rDNA. Primer selection is an important step, as anything that cannot be targeted by the primer will not be amplified and thus will not be detected, moreover different sets of primers can be selected to amplify different HVRs in the gene, or pairs of them. The appropriate choice of which HVRs to amplify has to be made according to the taxonomic groups of interest, as different target regions has been shown to influence taxonomical classification.[63]

Targeted studies of eukaryotic and viral communities are limited[64] and subject to the challenge of excluding host DNA from amplification and the reduced eukaryotic and viral biomass in the human microbiome.[65]

After the amplicons are sequenced, molecular phylogenetic methods are used to infer the composition of the microbial community. This can be done through clustering methodologies, by clustering the amplicons into operational taxonomic units (OTUs); or alternatively with denoising methodologies, identifying amplicon sequence variants (ASVs).

Phylogenetic relationships are then inferred between the sequences. Due to the complexity of the data, distance measures such as UniFrac distances are usually defined between microbiome samples, and downstream multivariate methods are carried out on the distance matrices. An important point is that the scale of data is extensive, and further approaches must be taken to identify patterns from the available information. Tools used to analyze the data include VAMPS,[66] QIIME,[67] mothur[68] and DADA2[69] or UNOISE3[70] for denoising.

Metagenomic sequencing edit

Metagenomics is also used extensively for studying microbial communities.[71][72][73] In metagenomic sequencing, DNA is recovered directly from environmental samples in an untargeted manner with the goal of obtaining an unbiased sample from all genes of all members of the community. Recent studies use shotgun Sanger sequencing or pyrosequencing to recover the sequences of the reads.[74] The reads can then be assembled into contigs. To determine the phylogenetic identity of a sequence, it is compared to available full genome sequences using methods such as BLAST. One drawback of this approach is that many members of microbial communities do not have a representative sequenced genome, but this applies to 16S rRNA amplicon sequencing as well and is a fundamental problem.[61] With shotgun sequencing, it can be resolved by having a high coverage (50-100x) of the unknown genome, effectively doing a de novo genome assembly. As soon as there is a complete genome of an unknown organism available it can be compared phylogenetically and the organism put into its place in the tree of life, by creating new taxa. An emerging approach is to combine shotgun sequencing with proximity-ligation data (Hi-C) to assemble complete microbial genomes without culturing.[75]

Despite the fact that metagenomics is limited by the availability of reference sequences, one significant advantage of metagenomics over targeted amplicon sequencing is that metagenomics data can elucidate the functional potential of the community DNA.[76][77] Targeted gene surveys cannot do this as they only reveal the phylogenetic relationship between the same gene from different organisms. Functional analysis is done by comparing the recovered sequences to databases of metagenomic annotations such as KEGG. The metabolic pathways that these genes are involved in can then be predicted with tools such as MG-RAST,[78] CAMERA[79] and IMG/M.[80]

RNA and protein-based approaches edit

Metatranscriptomics studies have been performed to study the gene expression of microbial communities through methods such as the pyrosequencing of extracted RNA.[81] Structure based studies have also identified non-coding RNAs (ncRNAs) such as ribozymes from microbiota.[82] Metaproteomics is an approach that studies the proteins expressed by microbiota, giving insight into its functional potential.[83]

Projects edit

The Human Microbiome Project launched in 2008 was a United States National Institutes of Health initiative to identify and characterize microorganisms found in both healthy and diseased humans.[84] The five-year project, best characterized as a feasibility study with a budget of $115 million, tested how changes in the human microbiome are associated with human health or disease.[84]

The Earth Microbiome Project (EMP) is an initiative to collect natural samples and analyze the microbial community around the globe. Microbes are highly abundant, diverse and have an important role in the ecological system. Yet as of 2010, it was estimated that the total global environmental DNA sequencing effort had produced less than 1 percent of the total DNA found in a liter of seawater or a gram of soil,[85] and the specific interactions between microbes are largely unknown. The EMP aims to process as many as 200,000 samples in different biomes, generating a complete database of microbes on earth to characterize environments and ecosystems by microbial composition and interaction. Using these data, new ecological and evolutionary theories can be proposed and tested.[86]

Gut microbiota and type 2 diabetes edit

The gut microbiota are very important for the host health because they play role in degradation of non-digestible polysaccharides (fermentation of resistant starch, oligosaccharides, inulin) strengthening gut integrity or shaping the intestinal epithelium, harvesting energy, protecting against pathogens, and regulating host immunity.[87][88]

Several studies showed that the gut bacterial composition in diabetic patients became altered with increased levels of Lactobacillus gasseri, Streptococcus mutans and Clostridiales members, with decrease in butyrate-producing bacteria such as Roseburia intestinalis and Faecalibacterium prausnitzii.[89][90] This alteration is due to many factors such as antibiotic abuse, diet, and age.

The decrease in butyrate production is associated with defects in intestinal permeability, which could lead to endotoxemia, which is the increased level of circulating Lipopolysaccharides from gram negative bacterial cells wall. It is found that endotoxemia has association with development of insulin resistance.[89]

In addition that butyrate production affects serotonin level.[89] Elevated serotonin level has contribution in obesity, which is known to be a risk factor for development of diabetes.

Gut microbiota development and antibiotics edit

The colonization of the human gut microbiota may start already before birth.[91] There are multiple factors in the environment that affects the development of the microbiota with birthmode being one of the most impactful.[92]

Another factor that has been observed to cause huge changes in the gut microbiota, particularly in children, is the use of antibiotics, associating with health issues such as higher BMI,[93][94] and further an increased risk towards metabolic diseases such as obesity.[95] In infants it was observed that amoxicillin and macrolides cause significant shifts in the gut microbiota characterized by a change in the bacterial classes Bifidobacteria, Enterobacteria and Clostridia.[96] A single course of antibiotics in adults causes changes in both the bacterial and fungal microbiota, with even more persistent changes in the fungal communities.[97] The bacteria and fungi live together in the gut and there is most likely a competition for nutrient sources present.[98][99] Seelbinder et al. found that commensal bacteria in the gut regulate the growth and pathogenicity of Candida albicans by their metabolites, particularly by propionate, acetic acid and 5-dodecenoate.[97] Candida has previously been associated with IBD [100] and further it has been observed to be increased in non-responders to a biological drug, infliximab, given to IBD patients with severe IBD.[101] Propionate and acetic acid are both short-chain fatty acids (SCFAs) that have been observed to be beneficial to gut microbiota health.[102][103][104] When antibiotics affect the growth of bacteria in the gut, there might be an overgrowth of certain fungi, which might be pathogenic when not regulated.[97]

Privacy issues edit

Microbial DNA inhabiting a person's human body can uniquely identify the person. A person's privacy may be compromised if the person anonymously donated microbe DNA data. Their medical condition and identity could be revealed.[105][106][107]

See also edit

References edit

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microbiota, other, uses, disambiguation, this, article, lead, section, short, adequately, summarize, points, please, consider, expanding, lead, provide, accessible, overview, important, aspects, article, october, 2018, range, microorganisms, that, commensal, m. For other uses see Microbiota disambiguation This article s lead section may be too short to adequately summarize the key points Please consider expanding the lead to provide an accessible overview of all important aspects of the article October 2018 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 2 3 and have been found to be crucial for immunologic hormonal and metabolic homeostasis of their host Diverse microbial communities of characteristic microbiota are part of plant microbiomes and are found on the outside surfaces and in the internal tissues of the host plant as well as in the surrounding soil 1 The term microbiome describes either the collective genomes of the microbes that reside in an ecological niche or else the microbes themselves 4 5 6 The microbiome and host emerged during evolution as a synergistic unit from epigenetics and genetic characteristics sometimes collectively referred to as a holobiont 7 8 The presence of microbiota in human and other metazoan guts has been critical for understanding the co evolution between metazoans and bacteria 9 10 Microbiota play key roles in the intestinal immune and metabolic responses via their fermentation product short chain fatty acid acetate 11 Contents 1 Introduction 1 1 Types of microbe host relationships 1 2 Acquisition and change 2 Microbiota by host 2 1 Humans 2 2 Non human animals 2 3 Plants 3 Research 4 Co evolution of microbiota 5 Research methods 5 1 Targeted amplicon sequencing 5 2 Metagenomic sequencing 5 3 RNA and protein based approaches 6 Projects 7 Gut microbiota and type 2 diabetes 8 Gut microbiota development and antibiotics 9 Privacy issues 10 See also 11 ReferencesIntroduction edit nbsp The predominant species of bacteria on human skinAll plants and animals from simple life forms to humans live in close association with microbial organisms 12 Several advances have driven the perception of microbiomes including the ability to perform genomic and gene expression analyses of single cells and of entire microbial communities in the disciplines of metagenomics and metatranscriptomics 13 databases accessible to researchers across multiple disciplines 13 methods of mathematical analysis suitable for complex data sets 13 Biologists have come to appreciate that microbes make up an important part of an organism s phenotype far beyond the occasional symbiotic case study 13 Types of microbe host relationships edit Commensalism a concept developed by Pierre Joseph van Beneden 1809 1894 a Belgian professor at the University of Louvain during the nineteenth century 14 is central to the microbiome where microbiota colonize a host in a non harmful coexistence The relationship with their host is called mutualistic when organisms perform tasks that are known to be useful for the host 15 700 16 parasitic when disadvantageous to the host Other authors define a situation as mutualistic where both benefit and commensal where the unaffected host benefits the symbiont 17 A nutrient exchange may be bidirectional or unidirectional may be context dependent and may occur in diverse ways 17 Microbiota that are expected to be present and that under normal circumstances do not cause disease are deemed normal flora or normal microbiota 15 normal flora can not only be harmless but can be protective of the host 18 Acquisition and change edit The initial acquisition of microbiota in animals from mammalians to marine sponges is at birth and may even occur through the germ cell line In plants the colonizing process can be initiated below ground in the root zone around the germinating seed the spermosphere or originate from the above ground parts the phyllosphere and the flower zone or anthosphere 19 The stability of the rhizosphere microbiota over generations depends upon the plant type but even more on the soil composition i e living and non living environment 20 Clinically new microbiota can be acquired through fecal microbiota transplant to treat infections such as chronic C difficile infection 21 Microbiota by host edit nbsp Pathogenic microbiota causing inflammation in the lungHumans edit Main article Human microbiota The human microbiota includes bacteria fungi archaea and viruses Micro animals which live on the human body are excluded The human microbiome refers to their collective genomes 15 Humans are colonized by many microorganisms the traditional estimate was that humans live with ten times more non human cells than human cells more recent estimates have lowered this to 3 1 and even to about 1 1 22 23 24 25 In fact these are so small that there are around 100 trillion microbiota on the human body 26 The Human Microbiome Project sequenced the genome of the human microbiota focusing particularly on the microbiota that normally inhabit the skin mouth nose digestive tract and vagina 15 It reached a milestone in 2012 when it published initial results 27 Non human animals edit Amphibians have microbiota on their skin 28 Some species are able to carry a fungus named Batrachochytrium dendrobatidis which in others can cause a deadly infection Chytridiomycosis depending on their microbiome resisting pathogen colonization or inhibiting their growth with antimicrobial skin peptides 29 Newborn marsupials are born with histologically immature immune tissues and unable to mount their own specific immune defence They are therefore heavily reliant on their mother s immune system 30 and the milk 31 for their protection Most marsupials have pouches and their own microbiota changes throughout the reproductive stages oestrus birth oestrus and post oestrus 32 Some pouch and skin secretions have had antimicrobial peptides identified that presumably support the young at this vulnerable time In mammals herbivores such as cattle depend on their rumen microbiome to convert cellulose into proteins short chain fatty acids and gases Culture methods cannot provide information on all microorganisms present Comparative metagenomic studies yielded the surprising result that individual cattle possess markedly different community structures predicted phenotype and metabolic potentials 33 even though they were fed identical diets were housed together and were apparently functionally identical in their utilization of plant cell wall resources Mice have become the most studied mammalian regarding their microbiomes The gut microbiota have been studied in relation to allergic airway disease obesity gastrointestinal diseases and diabetes Perinatal shifting of microbiota through low dose antibiotics can have long lasting effects on future susceptibility to allergic airway disease The frequency of certain subsets of microbes has been linked to disease severity The presence of specific microbes early in postnatal life instruct future immune responses 34 35 In gnotobiotic mice certain gut bacteria were found to transmit a particular phenotype to recipient germ free mice that promoted accumulation of colonic regulatory T cells and strains that modulated mouse adiposity and cecal metabolite concentrations 36 This combinatorial approach enables a systems level understanding of microbial contributions to human biology 37 But also other mucoide tissues as lung and vagina have been studied in relation to diseases such as asthma allergy and vaginosis 38 Insects have their own microbiomes For example leaf cutter ants form huge underground colonies harvesting hundreds of kilograms of leaves each year and are unable to digest the cellulose in the leaves directly They maintain fungus gardens as the colony s primary food source While the fungus itself does not digest cellulose a microbial community containing a diversity of bacteria is doing so Analysis of the microbial population s genome revealed many genes with a role in cellulose digestion This microbiome s predicted carbohydrate degrading enzyme profile is similar to that of the bovine rumen but the species composition is almost entirely different 39 Gut microbiota of the fruit fly can affect the way its gut looks by impacting epithelial renewal rate cellular spacing and the composition of different cell types in the epithelium 40 When the moth Spodoptera exigua is infected with baculovirus immune related genes are downregulated and the amount of its gut microbiota increases 41 In the dipteran intestine enteroendocrine cells sense the gut microbiota derived metabolites and coordinate antibacterial mechanical and metabolic branches of the host intestinal innate immune response to the commensal microbiota 42 Fish have their own microbiomes including the short lived species Nothobranchius furzeri turquoise killifish Transferring the gut microbiota from young killfish into middle aged killifish significantly extends the lifespans of the middle aged killfish 43 Plants edit nbsp Routes of colonization of potato tubers by bacteria 44 See also Plant microbiome The plant microbiome was recently discovered to originate from the seed 45 Microorganism which are transmitted via seed migrate into the developing seedling in a specific route in which certain community move to the leaves and others to the roots 45 In the diagram on the right microbiota colonizing the rhizosphere entering the roots and colonizing the next tuber generation via the stolons are visualized with a red color Bacteria present in the mother tuber passing through the stolons and migrating into the plant as well as into the next generation of tubers are shown in blue 44 The soil is the main reservoir for bacteria that colonize potato tubers Bacteria are recruited from the soil more or less independent of the potato variety Bacteria might colonize the tubers predominantly from the inside of plants via the stolon The bacterial microbiota of potato tubers consists of bacteria transmitted from one tuber generation to the next and bacteria recruited from the soil colonize potato plants via the root 44 nbsp Light micrograph of a cross section of a coralloid root of a cycad showing the layer that hosts symbiotic cyanobacteria Plants are attractive hosts for microorganisms since they provide a variety of nutrients Microorganisms on plants can be epiphytes found on the plants or endophytes found inside plant tissue 46 47 Oomycetes and fungi have through convergent evolution developed similar morphology and occupy similar ecological niches They develop hyphae threadlike structures that penetrate the host cell In mutualistic situations the plant often exchanges hexose sugars for inorganic phosphate from the fungal symbiont It is speculated that such very ancient associations have aided plants when they first colonized land 17 48 Plant growth promoting bacteria PGPB provide the plant with essential services such as nitrogen fixation solubilization of minerals such as phosphorus synthesis of plant hormones direct enhancement of mineral uptake and protection from pathogens 49 50 PGPBs may protect plants from pathogens by competing with the pathogen for an ecological niche or a substrate producing inhibitory allelochemicals or inducing systemic resistance in host plants to the pathogen 19 Research editThe symbiotic relationship between a host and its microbiota is under laboratory research for how it may shape the immune system of mammals 51 52 In many animals the immune system and microbiota may engage in cross talk by exchanging chemical signals which may enable the microbiota to influence immune reactivity and targeting 53 Bacteria can be transferred from mother to child through direct contact and after birth 54 As the infant microbiome is established commensal bacteria quickly populate the gut prompting a range of immune responses and programming the immune system with long lasting effects 53 The bacteria are able to stimulate lymphoid tissue associated with the gut mucosa which enables the tissue to produce antibodies for pathogens that may enter the gut 53 The human microbiome may play a role in the activation of toll like receptors in the intestines a type of pattern recognition receptor host cells use to recognize dangers and repair damage Pathogens can influence this coexistence leading to immune dysregulation including and susceptibility to diseases mechanisms of inflammation immune tolerance and autoimmune diseases 55 56 Co evolution of microbiota editMain article Hologenome theory of evolution nbsp Bleached branching coral foreground and normal branching coral background Keppel Islands Great Barrier Reef Organisms evolve within ecosystems so that the change of one organism affects the change of others The hologenome theory of evolution proposes that an object of natural selection is not the individual organism but the organism together with its associated organisms including its microbial communities Coral reefs The hologenome theory originated in studies on coral reefs 57 Coral reefs are the largest structures created by living organisms and contain abundant and highly complex microbial communities Over the past several decades major declines in coral populations have occurred Climate change water pollution and over fishing are three stress factors that have been described as leading to disease susceptibility Over twenty different coral diseases have been described but of these only a handful have had their causative agents isolated and characterized Coral bleaching is the most serious of these diseases In the Mediterranean Sea the bleaching of Oculina patagonica was first described in 1994 and shortly determined to be due to infection by Vibrio shiloi From 1994 to 2002 bacterial bleaching of O patagonica occurred every summer in the eastern Mediterranean Surprisingly however after 2003 O patagonica in the eastern Mediterranean has been resistant to V shiloi infection although other diseases still cause bleaching The surprise stems from the knowledge that corals are long lived with lifespans on the order of decades 58 and do not have adaptive immune systems citation needed Their innate immune systems do not produce antibodies and they should seemingly not be able to respond to new challenges except over evolutionary time scales citation needed The puzzle of how corals managed to acquire resistance to a specific pathogen led to a 2007 proposal that a dynamic relationship exists between corals and their symbiotic microbial communities It is thought that by altering its composition the holobiont can adapt to changing environmental conditions far more rapidly than by genetic mutation and selection alone Extrapolating this hypothesis to other organisms including higher plants and animals led to the proposal of the hologenome theory of evolution 57 As of 2007 update the hologenome theory was still being debated 59 A major criticism has been the claim that V shiloi was misidentified as the causative agent of coral bleaching and that its presence in bleached O patagonica was simply that of opportunistic colonization 60 If this is true the basic observation leading to the theory would be invalid The theory has gained significant popularity as a way of explaining rapid changes in adaptation that cannot otherwise be explained by traditional mechanisms of natural selection Within the hologenome theory the holobiont has not only become the principal unit of natural selection but also the result of other step of integration that it is also observed at the cell symbiogenesis endosymbiosis and genomic levels 7 Research methods editTargeted amplicon sequencing edit Targeted amplicon sequencing relies on having some expectations about the composition of the community that is being studied In target amplicon sequencing a phylogenetically informative marker is targeted for sequencing Such a marker should be present in ideally all the expected organisms It should also evolve in such a way that it is conserved enough that primers can target genes from a wide range of organisms while evolving quickly enough to allow for finer resolution at the taxonomic level A common marker for human microbiome studies is the gene for bacterial 16S rRNA i e 16S rDNA the sequence of DNA which encodes the ribosomal RNA molecule 61 Since ribosomes are present in all living organisms using 16S rDNA allows for DNA to be amplified from many more organisms than if another marker were used The 16S rRNA gene contains both slowly evolving regions and 9 fast evolving regions also known as hypervariable regions HVRs 62 the former can be used to design broad primers while the latter allow for finer taxonomic distinction However species level resolution is not typically possible using the 16S rDNA Primer selection is an important step as anything that cannot be targeted by the primer will not be amplified and thus will not be detected moreover different sets of primers can be selected to amplify different HVRs in the gene or pairs of them The appropriate choice of which HVRs to amplify has to be made according to the taxonomic groups of interest as different target regions has been shown to influence taxonomical classification 63 Targeted studies of eukaryotic and viral communities are limited 64 and subject to the challenge of excluding host DNA from amplification and the reduced eukaryotic and viral biomass in the human microbiome 65 After the amplicons are sequenced molecular phylogenetic methods are used to infer the composition of the microbial community This can be done through clustering methodologies by clustering the amplicons into operational taxonomic units OTUs or alternatively with denoising methodologies identifying amplicon sequence variants ASVs Phylogenetic relationships are then inferred between the sequences Due to the complexity of the data distance measures such as UniFrac distances are usually defined between microbiome samples and downstream multivariate methods are carried out on the distance matrices An important point is that the scale of data is extensive and further approaches must be taken to identify patterns from the available information Tools used to analyze the data include VAMPS 66 QIIME 67 mothur 68 and DADA2 69 or UNOISE3 70 for denoising Metagenomic sequencing edit Main article Metagenomics Metagenomics is also used extensively for studying microbial communities 71 72 73 In metagenomic sequencing DNA is recovered directly from environmental samples in an untargeted manner with the goal of obtaining an unbiased sample from all genes of all members of the community Recent studies use shotgun Sanger sequencing or pyrosequencing to recover the sequences of the reads 74 The reads can then be assembled into contigs To determine the phylogenetic identity of a sequence it is compared to available full genome sequences using methods such as BLAST One drawback of this approach is that many members of microbial communities do not have a representative sequenced genome but this applies to 16S rRNA amplicon sequencing as well and is a fundamental problem 61 With shotgun sequencing it can be resolved by having a high coverage 50 100x of the unknown genome effectively doing a de novo genome assembly As soon as there is a complete genome of an unknown organism available it can be compared phylogenetically and the organism put into its place in the tree of life by creating new taxa An emerging approach is to combine shotgun sequencing with proximity ligation data Hi C to assemble complete microbial genomes without culturing 75 Despite the fact that metagenomics is limited by the availability of reference sequences one significant advantage of metagenomics over targeted amplicon sequencing is that metagenomics data can elucidate the functional potential of the community DNA 76 77 Targeted gene surveys cannot do this as they only reveal the phylogenetic relationship between the same gene from different organisms Functional analysis is done by comparing the recovered sequences to databases of metagenomic annotations such as KEGG The metabolic pathways that these genes are involved in can then be predicted with tools such as MG RAST 78 CAMERA 79 and IMG M 80 RNA and protein based approaches edit Metatranscriptomics studies have been performed to study the gene expression of microbial communities through methods such as the pyrosequencing of extracted RNA 81 Structure based studies have also identified non coding RNAs ncRNAs such as ribozymes from microbiota 82 Metaproteomics is an approach that studies the proteins expressed by microbiota giving insight into its functional potential 83 Projects editThe Human Microbiome Project launched in 2008 was a United States National Institutes of Health initiative to identify and characterize microorganisms found in both healthy and diseased humans 84 The five year project best characterized as a feasibility study with a budget of 115 million tested how changes in the human microbiome are associated with human health or disease 84 The Earth Microbiome Project EMP is an initiative to collect natural samples and analyze the microbial community around the globe Microbes are highly abundant diverse and have an important role in the ecological system Yet as of 2010 update it was estimated that the total global environmental DNA sequencing effort had produced less than 1 percent of the total DNA found in a liter of seawater or a gram of soil 85 and the specific interactions between microbes are largely unknown The EMP aims to process as many as 200 000 samples in different biomes generating a complete database of microbes on earth to characterize environments and ecosystems by microbial composition and interaction Using these data new ecological and evolutionary theories can be proposed and tested 86 Gut microbiota and type 2 diabetes editThe gut microbiota are very important for the host health because they play role in degradation of non digestible polysaccharides fermentation of resistant starch oligosaccharides inulin strengthening gut integrity or shaping the intestinal epithelium harvesting energy protecting against pathogens and regulating host immunity 87 88 Several studies showed that the gut bacterial composition in diabetic patients became altered with increased levels of Lactobacillus gasseri Streptococcus mutans and Clostridiales members with decrease in butyrate producing bacteria such as Roseburia intestinalis and Faecalibacterium prausnitzii 89 90 This alteration is due to many factors such as antibiotic abuse diet and age The decrease in butyrate production is associated with defects in intestinal permeability which could lead to endotoxemia which is the increased level of circulating Lipopolysaccharides from gram negative bacterial cells wall It is found that endotoxemia has association with development of insulin resistance 89 In addition that butyrate production affects serotonin level 89 Elevated serotonin level has contribution in obesity which is known to be a risk factor for development of diabetes Gut microbiota development and antibiotics editThe colonization of the human gut microbiota may start already before birth 91 There are multiple factors in the environment that affects the development of the microbiota with birthmode being one of the most impactful 92 Another factor that has been observed to cause huge changes in the gut microbiota particularly in children is the use of antibiotics associating with health issues such as higher BMI 93 94 and further an increased risk towards metabolic diseases such as obesity 95 In infants it was observed that amoxicillin and macrolides cause significant shifts in the gut microbiota characterized by a change in the bacterial classes Bifidobacteria Enterobacteria and Clostridia 96 A single course of antibiotics in adults causes changes in both the bacterial and fungal microbiota with even more persistent changes in the fungal communities 97 The bacteria and fungi live together in the gut and there is most likely a competition for nutrient sources present 98 99 Seelbinder et al found that commensal bacteria in the gut regulate the growth and pathogenicity of Candida albicans by their metabolites particularly by propionate acetic acid and 5 dodecenoate 97 Candida has previously been associated with IBD 100 and further it has been observed to be increased in non responders to a biological drug infliximab given to IBD patients with severe IBD 101 Propionate and acetic acid are both short chain fatty acids SCFAs that have been observed to be beneficial to gut microbiota health 102 103 104 When antibiotics affect the growth of bacteria in the gut there might be an overgrowth of certain fungi which might be pathogenic when not regulated 97 Privacy issues editMicrobial DNA inhabiting a person s human body can uniquely identify the person A person s privacy may be compromised if the person anonymously donated microbe DNA data 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A O Dor R King N Vogel T M 2011 The importance of metagenomic surveys to microbial ecology Or why Darwin would have been a metagenomic scientist Microbial Informatics and Experimentation 1 1 5 doi 10 1186 2042 5783 1 5 PMC 3348666 PMID 22587826 Ibrahim Nesma 2018 07 01 Gut Microbiota and Type 2 Diabetes Mellitus What is The Link Afro Egyptian Journal of Infectious and Endemic Diseases 6 2 112 119 doi 10 21608 aeji 2018 9950 ISSN 2090 7184 S2CID 3900880 Thursby Elizabeth Juge Nathalie 2017 06 01 Introduction to the human gut microbiota Biochemical Journal 474 11 1823 1836 doi 10 1042 BCJ20160510 ISSN 0264 6021 PMC 5433529 PMID 28512250 a b c Munoz Garach Araceli Diaz Perdigones Cristina Tinahones Francisco J December 2016 Microbiota y diabetes mellitus tipo 2 Endocrinologia y Nutricion in Spanish 63 10 560 568 doi 10 1016 j endonu 2016 07 008 PMID 27633134 Blandino G Inturri R Lazzara F Di Rosa M Malaguarnera L 2016 11 01 Impact of gut microbiota on diabetes mellitus Diabetes amp Metabolism 42 5 303 315 doi 10 1016 j diabet 2016 04 004 ISSN 1262 3636 PMID 27179626 Vandenplas Y Carnielli V P Ksiazyk J Luna M S Migacheva N Mosselmans J M amp Wabitsch M 2020 Factors affecting early life intestinal microbiota development Nutrition 78 110812 Korpela K Helve O Kolho KL Saisto T Skogberg K Dikareva E Stefanovic V Salonen A Andersson S de Vos WM Maternal Fecal Microbiota Transplantation in Cesarean Born Infants Rapidly Restores Normal Gut Microbial Development A Proof of Concept Study Cell 2020 Oct 15 183 2 324 334 e5 doi 10 1016 j cell 2020 08 047 Epub 2020 Oct 1 PMID 33007265 Korpela K Salonen A Saxen H Nikkonen A Peltola V Jaakkola T amp Kolho K L 2020 Antibiotics in early life associate with specific gut microbiota signatures in a prospective longitudinal infant cohort Pediatric Research 1 6 Schei K Simpson M R Avershina E Rudi K Oien T Juliusson P B amp Odegard R A 2020 Early Gut Fungal and Bacterial Microbiota and Childhood Growth Frontiers in pediatrics 8 658 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