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@Mossy thought you might want the new stuffs on the Microbe world in our guts. NEW NEW NEW lol
The gut microbiome plays an important role in digestion and nutrition
The evidence is mounting for the inextricable link between a host's microbiota, digestion, and metabolism. In an analysis of humans and 59 additional mammalian species, 16S rRNA sequences clustered together carnivores, omnivores, and herbivores in principal coordinate spacing, showing that community structures differ depending on diets[48]. Dietary changes in mice can also lead to significant changes in bacterial metabolism, especially small chain fatty acids and amino acids, in as little as one week[49], and can lead to large changes after only one day[50]. Importantly, the genetic diversity found within our gut microbiota allows us to digest compounds via metabolic pathways not explicitly coded for in the mammalian genome, greatly increasing our ability to extract energy from our diverse diets[51, 52].
Gut microbiota also seem to play an important role in obesity. Germ-free mice that receive a transplant of gut microbiota from conventional mice have an increase in adiposity without increasing food intake due to increased energy extraction from the diet and increased energy deposition into host adipocytes[53]. The two major microbial divisions, Firmicutes and Bacteriodetes, show different abundances depending on phenotype. Decreased Bacteriodetes and increased Firmicutes have been found in genetically obese mice (ob/ob) when compared to their lean counterparts[54], and the obesity phenotype can even be transferred to a germ-free but genetically wild-type mouse by way of the microbiota, and the phenotype is due to energy balance: bomb calorimetry of the fecal pellets reveal that the ob/ob mice extract more energy from their diet, and leave less behind in the feces[51]. Fascinatingly, the same effects hold true for another mouse model, the TLR5 knockout mice, which also become obese in some mouse facilities (but develop colitis in others, presumably due to differences in the background microbiota). The TLR5 knockout mice also produce a transmissible obesity phenotype, but no difference in the efficiency of energy harvest is involved. Instead, the altered microbiota somehow makes the mice hungrier, and their microbe-induced obesity can be cured by restricting the amount of food in their cages to that consumed by wild-type mice, as well as by antibiotics[55]. The correlation between microbes and obesity is perhaps best illustrated through weight loss. As different groups of human subjects were placed on either a fat-restricted or carbohydrate-restricted diet, their abundance of Bacteriodetes increased as their body weight decreased, transitioning from the signature ‘obese’ microbial community to a ‘lean’ community[56]. Thus, the modulation of a patient's microbiota might be a therapeutic option for promoting weight loss in obese patients or promoting weight gain in underweight children.
Surprisingly, the microbes that we ingest with our food might be providing our individual microbiome with new genes to digest new foods. Hehemann et al. found that a new class of glycoside hydrolases used to digest porphyran, a polysaccharide common in red algae, was also found in human stool samples as a gene in Bacteriodes plebeius. A closer examination of the stool metadata revealed that the stool samples containing the porphyran-digesting gene were only present in Japanese individuals; the gene was not found in the gut microbiome of the individuals of the United States. Why would a marine gene be found in human gut? The authors concluded that the seaweed common to the Japanese, but not American, diet contained the microorganism which transferred the genes to gut microbiome[57]. Thus, microbes have the ability to greatly increase the number of metabolic tools of the human gut, allowing us to digest an array of substrates.
Go to:
Plasticity of the Human Gut
Given the relative stability of the human gut microbiota, one key question is whether it is sufficiently plastic to allow well-defined interventions to improve health. As described above, the gut microbiota is fairly stable over time once established, at least compared to the differences between individuals. However, a number of studies demonstrate that external forces can alter the community of microbes located in the GI tract and antibiotics are an important example.
Antibiotics are mainly used to combat pathogenic bacterial species that reside within or have invaded a host, however the current generation of antibiotics are broad spectrum and target broad swaths of the normal microbiota as well. Thus, antibiotics significantly affect the host's innate gut microbiota. Three to four days after treatment with the broad-spectrum antibiotic ciprofloxacin the gut microbiota experience a decrease in taxonomic richness, diversity, and evenness[58, 59]. The large magnitude of changes in the gut microbiota demonstrated significant interpersonal variability. While the gut microbiota began to resemble it's pre-treatment state a week after treatment, differences between individuals were seen with regards to how closely the post-treatment community resembled the pre-treatment community, and some taxa failed to return to the community[59, 60]. Indeed, the reestablishment of some species can be affected for up to four years following antibiotic treatment[61]. Yet the overall recovery of the gut microbiota following antibiotic treatments suggests that there are factors within the community, biotic or abiotic, than promote community resilience, although these have yet to be elucidated.
Other antibiotics also tend to produce results that differ substantially between subjects[62, 63] and even body sites[64]. Because larger populations have not yet been studied, in part due to ethical issues with administration of antibiotics to healthy human subjects, the basis for these underlying differences has not yet been elucidated. Understanding the factors that determine the ability of a microbiota to resist and recover from perturbation, as well as understanding the factors that determine its current state, will be key to developing tools to assist in microbiome manipulation. For example, counter-intuitively, in rats the administration of antibiotics prior to cecal transplant actually reduces the chance that new microbes will establish[65].
One fascinating hint that the microbiota may be more plastic than imagined is the recent success of treatment of persistent Clostridum difficile infections via stool transplant, which has been successful in a number of studies[66-72], and in general the depauperate gut community produced during the C. difficile infection is replaced by the donor community[67, 73]. The success of this technique is remarkable, especially considering how little is known about the best community to supply. For example, is it better to receive the fecal community of a close relative or of a cohabiting individual, or perhaps to bank one's own stool before beginning antibiotic treatment so that it can be restored later? Is the same stool good for everyone, or do the vast differences in the microbiota imply that each person's microbes are specifically adapted relative to those they might receive from a donor? As with blood types, are there “universal donors” and “universal recipients”? These and many other questions remain to be answered.
Go to:
Conclusions and prospectus
As in every year since the initial sequencing of DNA, this year has resulted in an unprecedented growth in the amount of sequence data collected at an unprecedentedly low cost. Increasingly powerful tools used to extract meaningful patterns from this wealth of data have been developed or updated as well. Emerging technologies such as stool transplantation, 16S rRNA and whole-genome sequencing on the Illumina platform, the ability to transplant human microbial communities into mice with high efficiency even from frozen samples[50], and the creation of personalized culture collections[74] raises the prospect of a future in which therapies for individual humans are piloted in a battery of mice that are subjected to different treatments, and where leave-one-out experiments that reveal the effects of the deletion of individual species[74] or individual genes from within a species[75] allow insight into mechanism. Although the tools we have available are still imperfect (for example, the limited read length of today's high-throughput sequencing technologies limit the ability to detect bacterial species and strains, and analyses of viruses and eukaryotes are still very much an emerging frontier), the prospects for developing a mechanistic understanding of the factors that underlie the plasticity of the microbiome and then for manipulating the microbiome to improve health seem increasingly bright.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3426293/
The gut microbiome plays an important role in digestion and nutrition
The evidence is mounting for the inextricable link between a host's microbiota, digestion, and metabolism. In an analysis of humans and 59 additional mammalian species, 16S rRNA sequences clustered together carnivores, omnivores, and herbivores in principal coordinate spacing, showing that community structures differ depending on diets[48]. Dietary changes in mice can also lead to significant changes in bacterial metabolism, especially small chain fatty acids and amino acids, in as little as one week[49], and can lead to large changes after only one day[50]. Importantly, the genetic diversity found within our gut microbiota allows us to digest compounds via metabolic pathways not explicitly coded for in the mammalian genome, greatly increasing our ability to extract energy from our diverse diets[51, 52].
Gut microbiota also seem to play an important role in obesity. Germ-free mice that receive a transplant of gut microbiota from conventional mice have an increase in adiposity without increasing food intake due to increased energy extraction from the diet and increased energy deposition into host adipocytes[53]. The two major microbial divisions, Firmicutes and Bacteriodetes, show different abundances depending on phenotype. Decreased Bacteriodetes and increased Firmicutes have been found in genetically obese mice (ob/ob) when compared to their lean counterparts[54], and the obesity phenotype can even be transferred to a germ-free but genetically wild-type mouse by way of the microbiota, and the phenotype is due to energy balance: bomb calorimetry of the fecal pellets reveal that the ob/ob mice extract more energy from their diet, and leave less behind in the feces[51]. Fascinatingly, the same effects hold true for another mouse model, the TLR5 knockout mice, which also become obese in some mouse facilities (but develop colitis in others, presumably due to differences in the background microbiota). The TLR5 knockout mice also produce a transmissible obesity phenotype, but no difference in the efficiency of energy harvest is involved. Instead, the altered microbiota somehow makes the mice hungrier, and their microbe-induced obesity can be cured by restricting the amount of food in their cages to that consumed by wild-type mice, as well as by antibiotics[55]. The correlation between microbes and obesity is perhaps best illustrated through weight loss. As different groups of human subjects were placed on either a fat-restricted or carbohydrate-restricted diet, their abundance of Bacteriodetes increased as their body weight decreased, transitioning from the signature ‘obese’ microbial community to a ‘lean’ community[56]. Thus, the modulation of a patient's microbiota might be a therapeutic option for promoting weight loss in obese patients or promoting weight gain in underweight children.
Surprisingly, the microbes that we ingest with our food might be providing our individual microbiome with new genes to digest new foods. Hehemann et al. found that a new class of glycoside hydrolases used to digest porphyran, a polysaccharide common in red algae, was also found in human stool samples as a gene in Bacteriodes plebeius. A closer examination of the stool metadata revealed that the stool samples containing the porphyran-digesting gene were only present in Japanese individuals; the gene was not found in the gut microbiome of the individuals of the United States. Why would a marine gene be found in human gut? The authors concluded that the seaweed common to the Japanese, but not American, diet contained the microorganism which transferred the genes to gut microbiome[57]. Thus, microbes have the ability to greatly increase the number of metabolic tools of the human gut, allowing us to digest an array of substrates.
Go to:
Plasticity of the Human Gut
Given the relative stability of the human gut microbiota, one key question is whether it is sufficiently plastic to allow well-defined interventions to improve health. As described above, the gut microbiota is fairly stable over time once established, at least compared to the differences between individuals. However, a number of studies demonstrate that external forces can alter the community of microbes located in the GI tract and antibiotics are an important example.
Antibiotics are mainly used to combat pathogenic bacterial species that reside within or have invaded a host, however the current generation of antibiotics are broad spectrum and target broad swaths of the normal microbiota as well. Thus, antibiotics significantly affect the host's innate gut microbiota. Three to four days after treatment with the broad-spectrum antibiotic ciprofloxacin the gut microbiota experience a decrease in taxonomic richness, diversity, and evenness[58, 59]. The large magnitude of changes in the gut microbiota demonstrated significant interpersonal variability. While the gut microbiota began to resemble it's pre-treatment state a week after treatment, differences between individuals were seen with regards to how closely the post-treatment community resembled the pre-treatment community, and some taxa failed to return to the community[59, 60]. Indeed, the reestablishment of some species can be affected for up to four years following antibiotic treatment[61]. Yet the overall recovery of the gut microbiota following antibiotic treatments suggests that there are factors within the community, biotic or abiotic, than promote community resilience, although these have yet to be elucidated.
Other antibiotics also tend to produce results that differ substantially between subjects[62, 63] and even body sites[64]. Because larger populations have not yet been studied, in part due to ethical issues with administration of antibiotics to healthy human subjects, the basis for these underlying differences has not yet been elucidated. Understanding the factors that determine the ability of a microbiota to resist and recover from perturbation, as well as understanding the factors that determine its current state, will be key to developing tools to assist in microbiome manipulation. For example, counter-intuitively, in rats the administration of antibiotics prior to cecal transplant actually reduces the chance that new microbes will establish[65].
One fascinating hint that the microbiota may be more plastic than imagined is the recent success of treatment of persistent Clostridum difficile infections via stool transplant, which has been successful in a number of studies[66-72], and in general the depauperate gut community produced during the C. difficile infection is replaced by the donor community[67, 73]. The success of this technique is remarkable, especially considering how little is known about the best community to supply. For example, is it better to receive the fecal community of a close relative or of a cohabiting individual, or perhaps to bank one's own stool before beginning antibiotic treatment so that it can be restored later? Is the same stool good for everyone, or do the vast differences in the microbiota imply that each person's microbes are specifically adapted relative to those they might receive from a donor? As with blood types, are there “universal donors” and “universal recipients”? These and many other questions remain to be answered.
Go to:
Conclusions and prospectus
As in every year since the initial sequencing of DNA, this year has resulted in an unprecedented growth in the amount of sequence data collected at an unprecedentedly low cost. Increasingly powerful tools used to extract meaningful patterns from this wealth of data have been developed or updated as well. Emerging technologies such as stool transplantation, 16S rRNA and whole-genome sequencing on the Illumina platform, the ability to transplant human microbial communities into mice with high efficiency even from frozen samples[50], and the creation of personalized culture collections[74] raises the prospect of a future in which therapies for individual humans are piloted in a battery of mice that are subjected to different treatments, and where leave-one-out experiments that reveal the effects of the deletion of individual species[74] or individual genes from within a species[75] allow insight into mechanism. Although the tools we have available are still imperfect (for example, the limited read length of today's high-throughput sequencing technologies limit the ability to detect bacterial species and strains, and analyses of viruses and eukaryotes are still very much an emerging frontier), the prospects for developing a mechanistic understanding of the factors that underlie the plasticity of the microbiome and then for manipulating the microbiome to improve health seem increasingly bright.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3426293/
