Gut flora - Wikipedia
Intestinal bacteria play a crucial role in maintaining immune and .. colon where it is crucial in mediating the host–microbiota relationship . Our relationship with components of this mutualistic relationships, the hosts gain carbon . Representation of the diversity of bacteria in the human intestine. The healthy human body is home to some trillion bacteria. They are on From there a lifelong relationship with bacteria begins. • Although.
There are significant changes in the composition of your microbiota that depends on what you're eating. There are groups in Japan that eat seaweed and they have particular bacteria that can confer the capacity to degrade some of the carbohydrates in seaweed.
It would depend on where you live on the Earth and it would depend on your health history. So even within that realm there's probably a wide range of different changes. So you could have a healthy person from Greece and try to compare them with a healthy person that lives in Tibet.
Introduction to the human gut microbiota
They would both be healthy, they would have what we'd consider healthy microbiomes but the composition of those microbiomes still might change quite significantly. Then how does the gut bacteria influence the body's complex systems, like the immune system? There are parts of our immune system that are hidden deep inside our bodies but much of our immune system is outward facing.
So it's present at the surface of our bodies. So of course it can interact with these microbes that are found in the microbiota. A variety of different mechanisms are emerging for how the microbiota may be influencing the immune system. These microbiota are bacteria and they produce metabolites that can signal through the immune system, and this signalling is sometimes critical - you mentioned it in your introduction that bacteria are often involved in symbiosis. So this signalling can be a good thing for you.
But these bacteria sometimes are involved in pathogenesis and so the signalling can be bad. The signalling pathways, for example, the important ones are found deep in the distal gut of your body. It's been found, for example that bacteroides which we'll talk a little bit about later - they provide the capacity to produce short chain fatty acids.
These include things like acetic acid, propionic acid and butyric acid. Acetic acid, your listeners should of course know is present in vinegar.
It turns out when you eat vinegar as part of your diet it gets absorbed in the proximal part of your gut and it cannot penetrate deep into your distal gut. But the bacteria that live in the distal gut produce these short chain fatty acids including acetate, and it's been shown that the acetate can have a couple of functions. It can act as a food source for epithelial cells that line your gastrointestinal tract, nourishing them in what is actually a fairly nutrient poor environment because you've extracted all the goodies out early in your digestive tract.
Secondly these molecules act as signalling molecules. So, in particular a paper came out in where they demonstrated that acetate combined to a signalling protein called a G protein-coupled receptor on the surface of a subclass of T cells. These were T helper cells and it stimulates the T helper cell, and T helper cells are an important subclass of T cells that control other T cells.
T cells generally are a group of cells that play a central role in how we combat infection and the status of our immune system. We're talking about the human microbiome and the chemistry of gut microbes here on Up Close. The last 50 years of western diet has meant we're eating more processed foods and consuming an array of pharmaceutical drugs. There is an increase in heart disease, diabetes, even Autism Spectrum Disorder. Spencer, surely we would see a change in the ecosystem of the gut.
So is there any correlation between these particular diseases and changes in the microbiome? So a big question has been is this just a correlation that's coincidental or is there a cause?
A change in the composition of your microbiome somehow causing these diseases. Increasingly the answer for some of these diseases appears to be yes. There was a lovely study done about half a decade ago where they took a rat that was genetically predisposed to becoming obese and they did a transplant of microbiome from its gut into a lean mouse and they were able to show that the lean mouse, simply by changing the nature of the microbiome in its gut, became more obese.
So I think that's a really nice clear example where the composition of the microbiome has a big effect on what we consider a very complex problem like obesity. There's many other examples that are becoming identified and the particular one that I have an interest in is Crohn's disease. Crohn's disease is an autoimmune disease that's poorly understood but it leads to poor bowel function, usually diarrhoea, regular passage, often many trips to the toilet every hour, let alone many trips to the toilet every day.
So it's a severe debilitating disease that has a profound effect on those suffering from it. Crohn's disease is often caused by a bacterium Clostridium difficile, so the basis of that disease is fairly clear in many cases that it's Clostridium difficile that's causing the problem. People with Crohn's diseases often have more of that bug, people that don't have Crohn's disease either have none of that bug or only a little bit of it.
That is, how does the microbiome respond to foods like artificial sweeteners? The body has never encountered these molecules before, how does it cope? Artificial sweeteners are an interesting thing that's become common in our diets since the s. An interesting point about artificial sweeteners is that it doesn't seem to have an impact on the amount of sugar that we eat. We seem to have an insatiable appetite for sweetened foods, even if we take artificial sweeteners we still tend to consume significant amounts of normal sweeteners like sucrose.
But this recent study looked at the effect on animals that were fed diets containing artificial sweeteners. So things like aspartame and saccharin, which I guess is now banned, and sucralose and related artificial sweeteners.
They showed that rats and mice fed these artificial sweeteners induced metabolic syndromes, a metabolic syndrome encompasses a wide variety of different conditions that include obesity and Type 2 diabetes. It appears from this study that consumption of these artificial molecules that are present in artificial sweeteners was one of the causes for the induction of metabolic syndrome. So the outcome of this study was that these artificial sweeteners correlated to an increase in obesity and diabetes, this was done in animals so whether or not this transfers into humans is an open question but it's something that definitely needs additional study.
Can we create good environments like the sort of prebiotic approach? This effect has no genetic influence and it is consistently observed in culturally different populations. In humans, research has shown that microbial colonization may occur in the fetus  with one study showing Lactobacillus and Bifidobacterium species were present in placental biopsies.
Various methods of microbiome restoration are being explored, typically involving exposing the infant to maternal vaginal contents, and oral probiotics. In humans, a gut flora similar to an adult's is formed within one to two years of birth. In most cases B cells need activation from T helper cells to induce class switching ; however, in another pathway, gut flora cause NF-kB signaling by intestinal epithelial cells which results in further signaling molecules being secreted.
It has been shown that IgA can help diversify the gut community and helps in getting rid of bacteria that cause inflammatory responses. For example short-chain fatty acids SCFA can be produced by some gut bacteria through fermentation.
Tryptophan metabolism by human gastrointestinal microbiota.
Introduction to the human gut microbiota
This effect is mostly limited to stratification and compartmentalisation of bacteria to avoid opportunistic invasion of host tissue, whilst species-specific effects are less probable due to the high amount of functional redundancy within the microbiota [ 52— ]. Both host-derived and administered antimicrobials play a key role in shaping the gut microbiota.
These proteins are localised in the mucus layer and are virtually absent from the lumen, probably either due to poor diffusion through mucus or luminal degradation [ 51]. Many secreted antimicrobial proteins AMPs kill bacteria through direct interaction with, and disruption of the bacterial cell wall or inner membrane via enzymatic attack [ 51 ]. Secretory IgA SIgAanother component of the immune system, co-localises with gut bacteria in the outer mucus layer and assists in limiting the exposure of the epithelial cell surface to bacteria .
SIgA is proposed to mediate bacterial biofilm formation via binding to SIgA receptors on bacteria [ ]. Dysbiosis of the microbiota, in particular an over-representation of segmented filamentous bacteria SFBoccurs in mice deficient in IgA, an effect that may be particularly damaging to the host due to the ability of SFB to strongly adhere to the epithelium and activate the immune system [ ]. Several environmental factors have been implicated in shaping the microbiota including geographical location, surgery, smoking, depression and living arrangements urban or rural [ 24— ].
Xenobiotics, such as antibiotics but not host-targeted drugs, shape the physiology and gene expression of the active human gut microbiome [ ]. Antibiotic treatment dramatically disrupts both short- and long-term microbial balance, including decreases in the richness and diversity of the community. Clindamycin [ ], clarithromycin and metronidazole [ 47 ], and ciproflaxin [ 33 ] have all been demonstrated to affect the microbiota structure for varying lengths of time.
The exact effects and the time for recovery of the microbiota following antibiotic administration appear to be individual-dependent, a likely effect of the inter-individual variation in the microbiota prior to treatment [ 3347].
Recent investigations in mice demonstrated that microbiota depletion by antibiotics affected secondary bile acid and serotonin metabolism in the colon, resulting in delayed GI motility [ ]. Antibiotic-treated mice are also more susceptible to pathogenic infection by antibiotic-associated pathogens, S. Role of the GI microbiota in health Owing to its large genomic content and metabolic complement, the gut microbiota provides a range of beneficial properties to the host. Some of the most important roles of these microbes are to help to maintain the integrity of the mucosal barrier, to provide nutrients such as vitamins or to protect against pathogens.
In addition, the interaction between commensal microbiota and the mucosal immune system is crucial for proper immune function. Colonic bacteria express carbohydrate-active enzymes, which endow them with the ability to ferment complex carbohydrates generating metabolites such as SCFAs [ ].
Three predominant SCFAs, propionate, butyrate and acetate, are typically found in a proportion of 1: These SCFAs are rapidly absorbed by epithelial cells in the GI tract where they are involved in the regulation of cellular processes such as gene expression, chemotaxis, differentiation, proliferation and apoptosis [ ]. Acetate is produced by most gut anaerobes, whereas propionate and butyrate are produced by different subsets of gut bacteria following distinct molecular pathways [ ].
Butyrate is produced from carbohydrates via glycolysis and acetoacetyl-CoA, whereas two pathways, the succinate or propanediol pathway, are known for the formation of propionate, depending on the nature of the sugar [ ].
In the human gut, propionate is mainly produced by Bacteroidetes, whereas the production of butyrate is dominated by Firmicutes [, ]. For example, fermentation of starch by specialist Actinobacteria and Firmicutes, e. Eubacterium rectale or E. Propionate is primarily absorbed by the liver, whilst acetate is released into peripheral tissues [ ]. The role of SCFAs on human metabolism has recently been reviewed .
Butyrate is known for its anti-inflammatory and anticancer activities . Butyrate is a particularly important energy source for colonocytes [ ]. A decreasing gradient of butyrate from lumen to crypt is suggested to control intestinal epithelial turnover and homeostasis by promoting colonocyte proliferation at the bottom of crypts, whilst increasing apoptosis and exfoliation of cells closer to the lumen [ ]. Butyrate can attenuate bacterial translocation and enhance gut barrier function by affecting tight-junction assembly and mucin synthesis [ ].
SCFAs also appear to regulate hepatic lipid and glucose homeostasis via complementary mechanisms. In the liver, propionate can activate gluconeogenesis, whilst acetate and butyrate are lipogenic [ ]. SCFAs also play a role in regulating the immune system and inflammatory response [ ]. They influence the production of cytokines, for example, stimulating the production of IL, an interleukin involved in maintaining and repairing epithelial integrity [ ]. Butyrate and propionate are histone deacetylase inhibitors that epigenetically regulate gene expression .
SCFAs have also been shown to modulate appetite regulation and energy intake via receptor-mediated mechanisms [ ]. Microbial metabolites other than SCFAs have been reported to have an impact on intestinal barrier functions, epithelium proliferation and the immune system [ ].
The GI microbiota is also crucial to the de novo synthesis of essential vitamins which the host is incapable of producing [ ]. Lactic acid bacteria are key organisms in the production of vitamin B12, which cannot be synthesised by either animals, plants or fungi . Bifidobacteria are main producers of folate, a vitamin involved in vital host metabolic processes including DNA synthesis and repair [ ].
Further vitamins, which gut microbiota have been shown to synthesise in humans, include vitamin K, riboflavin, biotin, nicotinic acid, panthotenic acid, pyridoxine and thiamine [ ]. Colonic bacteria can also metabolise bile acids that are not reabsorbed for biotransformation to secondary bile acids [ ]. All of these factors will influence host health.
For example, an alteration of the co-metabolism of bile acids, branched fatty acids, choline, vitamins i. There are many lines of evidence in support of a role for the gut microbiota in influencing epithelial homeostasis [ 7 ].
Germ-free mice exhibit impaired epithelial cell turnover which is reversible upon colonisation with microbiota [ ]. A role has been demonstrated for bacteria in promoting cell renewal and wound healing, for example, in the case of Lactobacilli rhamnosus GG [ ]. Furthermore, several species have been implicated in promoting epithelial integrity, such as A. In addition to modulating epithelial properties, bacteria are proposed to modulate mucus properties and turnover.
Mice housed under germ-free conditions have an extremely thin adherent colonic mucus layer, but when exposed to bacterial products peptidoglycan or LPSthe thickness of the adherent mucus layer can be restored to levels observed in conventionally reared mice [ ]. It is proposed that these functions mediate the ability of other commensals or pathogens to colonise, potentially giving some commensal species a competitive advantage in the gut [ ].
The GI microbiota is also important for the development of both the intestinal mucosal and systemic immune system as demonstrated by the deficiency in several immune cell types and lymphoid structures exhibited by germ-free animals. This deficiency can be completely reversed by the treatment of GF mice with polysaccharide A from the capsule of B. This process is mainly performed via the pattern recognition receptors PRRs of epithelial cells, such as Toll-like or Nod-like receptors, which are able to recognise the molecular effectors that are produced by intestinal microbes.
These effectors mediate processes that can ameliorate certain inflammatory gut disorders, discriminate between beneficial and pathogenic bacteria or increase the number of immune cells or PRRs [ ]. SFB, a class of anaerobic and clostridia-related spore-forming commensals present in the mammalian GI tract, actively interact with the immune system [ ].
Unlike other commensal bacteria, SFB are closely associated with the epithelial lining of the mammalian GI tract membrane, which stimulates epithelial cells to release serum amyloid A1 [ ].
Colonisation with SFB may also direct post-natal maturation of the gut mucosal lymphoid tissue, trigger a potent and broad IgA response, stimulate the T-cell compartment and up-regulate intestinal innate defence mediators, suggesting immune-stimulatory capacities of SFB as reviewed in [ ].
Individuals with CD display mucosal dysbiosis characterised by reduced diversity of core microbiota and lower abundance of F. Recently, an anti-inflammatory protein from F. The physical presence of the microbiota in the GI tract also influences pathogen colonisation by, for example, competing for attachment sites or nutrient sources, and by producing antimicrobial substances [ 9 ].
Antibiotics have a profound impact on the microbiota that alter the nutritional landscape of the gut and lead to the expansion of pathogenic populations [ ].
Dietary fibre deficiency, together with a fibre-deprived, mucus-eroding microbiota, promotes greater epithelial access and lethal colitis by the mucosal pathogen Citrobacter rodentium in mice [ 83 ]. The GI microbiota, via its structural components and metabolites, also stimulates the host to produce various antimicrobial compounds.
The other mechanism by which the gut microbiota can limit pathogen overgrowth is by inducing mucosal SIgA [ ].