Human microbiota - Wikipedia
Symbiotic gut bacteria evolved and diverged along with ape and up a large portion of the gut microbiome and their primate hosts has “This paper sets the stage for the possibility that our mutualistic gut bacteria evolved at the same the difference between gorillas, chimpanzees, and humans, and so it. The adult human intestine is home to an almost inconceivable number of microorganisms. In these mutualistic relationships, the hosts gain carbon and energy, and only 8 of the 55 known bacterial divisions have been identified to date (Fig. . in much the same way as dense, well-settling, granular biofilms help oppose. New studies are revealing how the gut microbiota has co- evolved mutualistic relationships, the hosts gain carbon and energy . Ratios are the number of sequences represented in the human gut relative to .. same polysaccharide-rich .
We regularly eat small amount of fungus as part of our diet. So I guess it's not unexpected that our gut may have adapted to this change in our diet. This recent study that we published in Nature in demonstrated that there are special bacteria that exist in our guts that provide the capacity to break down cell wall components of yeast in our diet.
As I mentioned, humans have done a lot of domestication of different organisms and in fact this flows through in to other animal species. So we went looking for where this bacteria can be found and can it be found in other organisms.
In fact the only other place we were able to locate this bacteria were in pigs and they were located in a piggery adjacent to a brewery.
Of course a brewery, one of the by-products of a brewery is spent brewer's grain. So this is grain that's been fermented with yeast and it's an industrial by-product that you then feed to pigs and of course now these pigs have a history of consuming domesticated yeast and those pigs as well also had bacteria in the guts - that had the same capacity that we thought was uniquely in humans, well in fact it has spilled over to one animal species that we were able to identify.
When we consume foods, early in our digestive system we break down certain polysaccharides, so things like starch and sucrose, they get broken down and we use them as food. Other polysaccharides which include things like dietary fibre and in this case includes the cell wall of the yeast, pass through our gastrointestinal tract and reach our distal gut.
It's there where the bacteria lives and it uses the cell wall components of the yeast as a type of food. Now what our work has shown is that the bacterium has a really complex machinery of enzymes that are found on the surface of the bacteria that can trim these very complex structures in the yeast cell wall, then import them into what's called the periplasmic space, so a space between the outer wall and the inner wall, where they are then degraded down to individual monosaccharides, so just single sugars that are directly useable for energy.
You mentioned in your opening that these bacteria are involved in a symbiosis and in fact this bacteria produces those short chain fatty acids that I mentioned before. So upon digesting the yeast cell wall and in fact other polysaccharides, they produce a wide range of short chain fatty acids which are then released and that nourishes our cell wall.
One of the interesting components of our study was sometimes Bacteroides thetaiotaomicron, acts as a keystone species and other bacteria can live around it. But in particular with this component of the yeast cell wall it has a selfish mechanism, it takes it up exclusively and does not release anything out. So this idea of a particular food source that can only be utilised by a particular bacterial strain may have uses in biotechnology and possibly in treating human health.
So how does this relate to Crohn's disease? It's a fairly complex story but let's slowly work through the issues. So the direct correlation is perhaps not there but there's lots of interesting connections. Patients with Crohn's disease often have a marker antibody that they produce called the ASCA antibody.
So people with severe Crohn's disease often have an anti-body that's against yeast. What does this antibody recognise specifically within yeast? Well it recognises the same structures that we've shown that this organism, Bacteroides thetaiotaomicron has the capacity to degrade.
So if you try to think about what might Bt provide, it might provide the ability to degrade this carbohydrate in the cell wall of the yeast so that it cannot be recognised by the immune system and it may not give rise to autoimmunity.
If that would be the case then one might think that people with Crohn's disease might have less of this bug which might lead to them having more yeast in their gut and that might lead to these autoimmune responses and people that are healthy that don't have Crohn's disease might have more of this bug and consequently they have less yeast cell wall because it's all been consumed.
Indeed that seems to be the case. What does that exactly mean and what does that entail? So if you imagine how debilitating it is for adults it's particularly debilitating for children. So Bt has been granted orphan drug status because there are no other treatments.
So this is a debilitating disease that there are really no options to treat these children. So this company is investigating the use of Bt as a bacteriotherapy to restore a normal microbiome composition and hopefully overcome the problems of Crohn's disease.
But this case of Crohn's disease I think it's emerging that there is a stronger link. People are consuming yeast, if it's not degraded in their bowel, you're generating an immune response against it and somehow that's causing a change in your immune status and that causes the symptoms of Crohn's disease.
If indeed that is the case then a bacteria that has the ability to degrade the yeast cell wall and not produce the so-called epitopes, the parts of the yeast cell wall that are recognised by the immune system could be a way of treating these people or allowing them to manage their symptoms.
So when we're thinking about prebiotic strategies, is it possible to feed yeast deliberately to somebody to encourage the growth of Bt?
Now in fact yeast is easily genetically manipulated and the particular cell wall structure that we're dealing with here, the mannan, there are many mutants available that have all sorts of different structure and we showed that some of these mutants have better effects on growth than others. What I wonder is, whether genetically engineered forms of yeast that produce certain cell wall structures might be able to be added to our diet and whether they might encourage the growth of helpful beneficial populations of Bt in our gut.
So if we were then to have a person who's in need of a regular dose of a drug to keep them healthy, perhaps we could inoculate them with a genetically engineered form of Bt that could then populate their gut and we could be certain that that bacteria would keep living in that gut by ensuring that they eat a particular form of yeast that we now know acts through a selfish mechanism. And a nice part of that idea could be, we could then remove the yeast from the diet and clear out the bacterial strain from their gut when they no longer need that drug.
But when it comes to gut microbes, can you explain to us why are these important molecules? So we've all heard of carbohydrates, well in fact carbohydrates is a very general term and we can break carbohydrates up into two groups. Those that we can digest which includes things like starch and sucrose, and those that we can't digest which can include something like wood, cellulose and soluble dietary fibre like Beta-1 3-d glucan that you find in oats. So it turns out that many of the bugs in our gut survive on what we consider non-digestible carbohydrates, this would make sense.
Of course in our gut we consume the digestible ones and that provides us with energy, what are these bacteria going to live on? Well they have the capacity to degrade so called non-digestible carbohydrates and so this is their major food source.
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- Host–Bacterial Symbiosis in Health and Disease
In fact it's not quite as simple as that. As I mentioned before there's a symbiosis that when these bugs degrade these non-digestible carbohydrates they release short chain fatty acids which we use as food and it's been estimated that we derive around 10 per cent of our caloric intake from bugs digesting so called indigestible carbohydrates and supplying them to us as part of that symbiosis.
You also mentioned in your introduction that there are many more genes encoded by the bacteria that live in our gut than we have genes encoded ourselves so in fact these bacteria have a rich capacity to degrade almost every single carbohydrate that you could imagine that is in your diet and convert them into a beneficial food source. Humans are omnivores, we change what we eat every day, between meals. So these bacteria, particularly in humans, have evolved this capacity to be generalist, so called glycan generalist and break down lots of different types of carbohydrates depending on your whim of today, whether you're going to have a sandwich or muesli.
Most of which are harmless or even beneficial to human host. Colonization on skin is highly variable depending on endogenous host factors, topographical location and exogenous environmental factors. Symbiotic microorganisms occupy a wide range of skin niches and protect against invasion by more pathogenic or harmful organisms. One example of bacteria that protects the skin is Bacillus subtilis. It produces bacitracin on the skin, a toxin poison that helps it in fighting with other microbes.
The property of bacitracin to act as an antibacterial agent has been exploited to use it as antibiotics. Skin microflora may also have a role in educating the billions of T cells, priming them to respond to similarly marked pathogen [ 4 ]. Primary bacterial colonizers are Staphylococcus epidermidis and other coagulase-negative Staphylococci. Other microorganisms that are generally regarded as skin colonizers are species of CorynebacteriumPropionibacterium and Brevibacterium.
The most commonly isolated fungal species is Malassezia sp. The Demodex mites viz. Demodex folliculorum and Demodex brevis are microscopic arthropods and these are also regarded as part of the normal skin flora [ 5 ]. Microbes in Nasal Cavity A little is known about the microbes in nasal cavity. However, evidences suggested that microbiota of the nasal cavity plays a crucial role in determining the reaction patterns of the mucosal and systemic immune system.
Different microbiota are found in different parts of the nasal cavity. Many studies are conducted to know about the microbiota of nasal cavity. The studies suggested absence of Gramnegative bacteria in nasal passage that are regularly present in pharynx. However, viridans type Streptococci are sparsely present in the nasal cavity. On the other hand, species of CorynebacteriumAureobacteriumRhodococcus and Staphylococcus have been found to be present dominantly.
These data suggested that microbiota present in of the nasal cavity of adult humans are strikingly different from that of the pharynx [ 6 ]. The anaerobic bacteria found were Propionibacterium acnes in The microorganisms found in the human oral cavity are called as the oral microflora, oral microbiota or oral microbiome.
This microflora comprises over species with distinct combination at different habitats. Most organisms that are colonizing are beneficial to human health but some microbes transit from a commensal relationship to pathogenicity.
The reasons for the transition are not understood, however it is believed that it may be because of changes in the environment or personal hygiene [ 8 ]. Scientists have found the agonist as well as antagonist interactions between these microbes. For example, interaction between Streptococcus gordonii and Actinomyces naeslundii are both agonist and antagonist in nature.
Both these microbes are involved in biofilm production.
Primates, Gut Microbes Evolved Together | The Scientist Magazine®
Conversely, hydrogen peroxide produced by S. Another example of antagonist relationship is of Streptococcus mutanswhich is a leading cause of dental caries. It uses quorum sensing and releases bacteriocin when introduced to other bacteria while StreptococcusActinomycesand Lactobacillus generate an acidic pH, which results in inhibition of growth of a variety of bacterial species [ 1011 ].
Microbes in Human Gut The human gut serves two major functions: Polysaccharide utilization and host—microbe interaction shaping the gut microbiota Bacteroides thetaiotaomicron is one of the most extensively studied symbionts of the human gut. One of the first evidences of gut microbiota playing an active role in host biology was demonstrated by the pioneering work of Hooper et al.
Host genes that were upregulated upon B. Together, these genes demonstrate that commensal bacteria can help fortify the host epithelial barrier. Other host genes affected by mono-association with B. This study demonstrated how a single species of commensal organism may restore many of the structural, metabolic, and developmental defects of a previously germ-free host.
When the whole genome of B. However, it has evolved paralogs of two outer membrane polysaccharide-binding proteins SusC and SusDpredicted glycoside hydrolases, and 15 polysacchride lyases. Whole-genome transcriptional profiling of B. The glycan-foraging behavior of the gut symbiont was further explored by comparing the bacterial gene expression in germ-free mice maintained either on a standard polysaccharide-rich chow diet or on a simple sugar diet devoid of fermentable polysaccharide.
These genes may also serve to mediate bacterial attachment to mucus glycans to avoid bacterial washout from the gut Xu and Gordon, ; Xu et al. Another noteworthy gene expression change during growth in vitro versus in vivo and with diet manipulation was found in the capsular polysaccharide synthesis CPS loci, indicating that B. The ability to salvage energy from nutrients that are otherwise nondigestible by the host provides an evolutionary driving force for the bacteria to maintain residency in the host intestine.
Although it lacks adhesive organelles, B. Due to its flexible glycan-foraging ability, B. This highly successful human gut symbiont has evolved an elaborate and sizable genome that can mobilize functionally diverse adaptive responses to changing nutrient environment and thus guarantee a permanent and mutualistic association with its host.
Role of host immunity in shaping the gut microbiota Commensal bacterial colonization of the host digestive tract has been shown to induce expression of a number of genes Bry et al. One of the strategies used by commensal bacteria to maintain a favorable environment and to influence gut microbial ecology at the detriment of other competing and often pathogenic bacteria is inducing and modulating host innate immunity Kelly et al.
One example is the induction of antimicrobial proteins including angiogenin-4 Ang4 Hooper et al. Ang4 is a novel class of antimicrobial peptides secreted from Paneth cells and has microbicidal effects against several Gram-positive pathogens while leaving B. Commensal bacteria of the gut frequently come in contact with the host innate immune system and often cross the epithelial barrier during the sampling of luminal contents by dendritic cells Macpherson and Harris, When laden with commensal bacteria, dendritic cells traffic to local mesenteric lymph nodes, where they activate cells of the adaptive immune system and induce secretion of protective IgA antibodies that coat luminal microbes and prevent them from breaching the epithelium.
In contrast, dendritic cells carrying pathogens travel throughout the body and elicit systemic immune responses Macpherson and Uhr, ; Macpherson et al. The bacterial signals that give rise to these different dendritic cell behaviors are not known but since heat-killed indigenous bacteria do not elicit this behavior, MAMPs are not likely to be involved in distinguishing between commensal and pathogenic bacteria Macpherson and Uhr, Using an experimental gnotobiotic animal model harboring genetic immune deficiency, Peterson et al.
A model symbiont B. The presence of IgA reduced intestinal proinflammatory signaling as well as bacterial epitope expression. In another study, mice deficient in activation-induced cytidine deaminase AIDan essential enzyme for immunoglobulin class switching and somatic hypermutation, showed significant change in the composition of the gut microbiota wherein the segmented filamentous bacteria SFB greatly expanded Suzuki et al.
This dysregulation was recovered by the presence of normal hyper-mutated IgA. These studies suggest that IgA plays a critical role in mediating tolerance in the gut, regulating the gut bacterial composition, and maintaining intestinal homeostasis between host and microbe.
Mucosal surface colonization by commensal bacteria The mucosal surface of the mammalian distal gut provides a vast surface area where gut microbes come in contact with the host. Understanding the host—microbe interaction at the mucosal surface is fundamental to uncovering colonization mechanisms of commensal bacteria in the gut.
However, due to the diverse nature of the gut resident bacteria and the environmental complexity found on the gut mucosal surface, it is highly unlikely that all commensal bacteria colonize the mucus layer through the same mechanism. Moreover, studying the interactions between host and bacteria through the thickness of the mucus layer in vivo has proven to be a formidable task.
Our current understanding of how certain bacteria interact within the mucus layer is mainly limited to in vitro bacterial mucin-binding studies which may not recapitulate inside the host intestinal tract.
The mucus gel layer of the large intestine is a dense matrix of polysaccharides and proteins derived mainly from the goblet cell lineage of the epithelium. Its thickness and mucin composition vary along the length of the gut Matsuo et al. Mucins are high-molecular-weight glyco-proteins characterized by extended serine, threonine, and proline-rich domains in the protein core, which are sites of extensive O-linked glyco-sylation with oligosaccharides Lievin-Le Moal and Servin, Traditionally, the mucus gel layer is considered a buffer between the highly immunogenic luminal contents commensals and pathogens alike and the host epithelial layer serving to protect both the host and the gut bacteria Deplancke and Gaskins, On the contrary, the mucus layer can represent a habitat and source of nutrients for the bacterial communities that colonize mucosal surfaces Sonnenburg et al.
The principal components of mucus include the large, complex mucin, a variety of smaller proteins and glycoproteins, and lipids and glycolipids secreted by epithelial cells, all of which can provide an excellent source of nutrients and energy for bacterial growth and colonization.
The ability of mucus to support the growth of bacteria is evident from numerous in vitro studies in which bacteria have been shown to grow readily in mucus preparations Jonsson et al. Using a streptomycin-treated mouse model, Chang et al. Initially, whole-genome transcriptional profiling of E. Several nutritional genes corresponding to catabolic pathways for nutrients found in mucus were induced. Each pathway was systematically knocked out and mutants were tested for fitness in mouse intestinal colonization.
Primates, Gut Microbes Evolved Together
Competitive colonization between wild-type MG and isogenic mutants that lack the ability to catabolize various nutrients confirmed that carbohydrate catabolism plays a dominant role in the initiation and maintenance of E. Nutrient availability within the colon mucus layer creates an attractive ecological niche for bacteria and thus provides at least one likely mechanism of gut colonization by commensal bacteria.
Physical and biochemical analysis of mouse colonic mucus revealed two distinct layers, an inner adherent layer that is firmly adherent to the intestinal mucosa and an outer layer that can be washed off with minimal rinsing Johansson et al. Both layers are largely formed by MUC2, a major secretory mucin in humans and mice Allen et al.
However, visual analysis by fluorescence in situ hybridization using a universal probe against bacteria reveals the outer layer is heavily colonized with bacteria while the inner layer is virtually sterile Johansson et al.Human Symbiosis with Viruses
This two-layer structure may reconcile the seemingly contrasting functional roles of the colon mucus layer—the loose outer layer seems to provide an ideal habitat for the commensal bacteria while the inner firmly attached mucus layer forms a specialized physical barrier between the commensal bacteria and the host tissue. Analysis of carbohydrate structures along the length of the gastrointestinal tract of two humans showed that although their mucin-associated glycans were diverse, their region-specific glycosylation patterns were well conserved Robbe et al.
These glycoproteins and mucoproteins on the mucosal surface of the host gut can serve as receptor sites for attachment and adherence by commensal bacteria Baranov and Hammarstrom, ; Granato et al. High diversity among the glycans with conserved spatial patterns found on the gut mucosal surface strongly suggests a mechanism of host-driven perhaps as a result of bacteria modulating the host regulation of gut microbial community composition by directing members of the microbiota to distinct host niches by serving as nutrient sources or docking sites for these organisms.
Overview of the mucosal immune system Mammalian success depends on the ability to actively clear or contain anything that is detected as infectious nonself. Therefore, the systemic immune system evolved with a very simple goal: However, within the mammalian gastrointestinal tract, where an astonishing trillion microbes establish residence, a different set of guidelines dictate the function of the mucosal immune system. Here the greatest benefit and thus success of the host depends not on sterility, but rather on maintenance of the symbiotic relationship between the host and the intestinal microbiota.
Proper development, maturation, and function of the mammalian gastrointestinal track are dependent on contributions by the commensal flora. Germ-free animals that have been raised in the complete absence of microbial exposure present with undeveloped tissue architecture, deficiency in nutrient and vitamin absorption, as well as significant susceptibility to gastrointestinal infection Dethlefsen et al.
With multiple aspects of host development and health relying so heavily on the microbiota, it is critical that a system is in place that is able to actively maintain this mutualistic partnership.
This responsibility falls in the hands of the mucosal immune system. While the systemic immune system is designed to react in almost an automatic fashion to any microbial agent it detects, the mucosal immune system must be more tentative in its response so as to preserve the critical partnership with the gut bacteria.
However, the presence of this large microbial mass, in such proximity to host tissue, poses a potential and serious threat of infection. Additionally, there is always the risk of infection by acquired, noncommensal gastrointestinal pathogens.
Therefore, the challenge to the mucosal immune system is to selectively and actively tolerate the gut microbiota during steady-state conditions when there is a low threat of infection while being able to mount an appropriate inflammatory response during an incidence of disease or infection. Similarly, it is to the benefit of the microbiota to avoid initiating an inflammatory response in order to maintain its nutrient-rich niche. However, once the microbiota is under immune attack, a more virulent or pathogenic profile may provide certain microbial species with a greater chance of success.
The mammalian host and intestinal microbiota, in effect, are establishing a cooperative system that exists only as long as the individual costs for maintaining the collaboration are lower than the benefits received. The mucosal immune system and microbiota form a cooperative system A cooperative system consists of two or more players who each pay a cost so that the other player can receive a benefit Nowak, The decision to cooperate depends on multiple factors including the type of relationship between the players, the cost versus benefit ratio, and the option of exacting an equal or greater benefit through an alternative source Dethlefsen et al.
Game theory, a field of applied mathematics, analyzes such standoffs to provide strategies, in a given scenario, that will predict the greatest success for individual players. Within this field, several cooperative systems have been described that are defined by the type of relationship linking the players and the conditions by which cooperation is maintained.
Of these systems, the one that most resembles the mammalian-microbial symbiosis is the generous tit-for-tat cooperation system Nowak, ; Perru, Within this system, two unrelated players form a collaborative alliance to exact a mutual benefit, until one player breaks the trust leading to dissolution of the cooperative system.
In the case of intestinal microbiota and mucosal immune system, both parties work to actively maintain tolerance, thus allowing for the benefits of the mutualistic partnership to be realized. This collaboration comes to an end, however, once there is a threat of disease caused either by aberrant immune activation or infection where now the costs of maintaining the cooperative system are greater than the benefits received.
By ascribing the generous tit-for-tat system to mucosal immune system and intestinal microbiota, we wish to highlight the differences in the goals between the mucosal and systemic immune system, as well as provide insight into how this cooperative system is maintained over time, despite episodes of defection by both party members. Immune plasticity is necessary to maintain cooperation over time One should be able to appreciate the multiple mechanisms that have evolved, by both the host and the microbiota, to maintain or suspend their mutualistic partnership.
This wide arsenal of toleragenic and inflammatory mediators is necessary as the decision to cooperate or defect is under continuous deliberation by both parties, where the costs of maintaining such an alliance are assessed.
During incidences of disease, which inflate the costs of cooperation such that individual host or microbial fitness is threatened, a pause is placed on the partnership while various mediators host and microbial collaborate to reestablish intestinal homeostasis.
This back and forth between tolerance and immunity, cooperation and defection, implies mechanisms of plasticity within the host and microbial response are necessary for protection from disease as well as maintenance of the cooperative system over time Edwards, ; Ulvestad, ; van Baalen, Accordingly, mathematical models of host—microbial interactions demonstrate that conditions where players are allowed to alter their actions, in response to one another, promote the evolution of commensalism, as compared to conditions where actions are fixed Taylor et al.
Applying this concept to the host, plasticity in immune development can be viewed as a mechanism of negotiating alliance between the host and the microbiota, in conditions of steady state and disease, allowing for the maintenance of a mutualism over time that is critical to both parties. Several recent reports have shown the ability of various T cell sub-populations to redifferentiate into cells that differ in cytokine expression and functional profile.
This conversion of Th2 cells, which required antigen presentation and IL cytokine stimulation, into Th1Th2 hybrid cells allowed for viral clearance and prevented viral-mediated immunopathology. These two examples demonstrate the ability of effector T cells to alter their expression profile, possibly to tailor a specific response to a particular microbial agent.
In addition to T effector cells, T regulatory cells have been recently shown to adopt a proinflammatory profile, implicating the need to establish an immunogenic response to an agent once tolerated. These exFoxp3 cells adopted an activated memory phenotype CD44hi as well as the expression of proinflammatory cytokines that were environment-specific.
The study additionally demonstrated an increased ratio of exFoxp3 to Foxp3 positive cells during states of inflammatory disease.
To explore the functional properties of these cells, BDC2.