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hey @pop22 you may want to give some of these a read and hang around for some findings. prolly precursor ones out potentially. dont know exactly how long its been going on.but a cpl years or so now 
Introduction
Microorganisms in the human gut encompass hundreds to thousands of bacterial, archaeal, viral and fungal species, making the human intestinal lumen a rich and dense source of antigenic diversity1. The gut mucosal immune system samples and processes these microbial antigens, potentially driving the expansion of particular immune subsets or generating specific immune repertoires2. Thus, the intestinal microbiome is an important entity within the host that influences immune responses both locally and systemically.
The gut microbiome has been implicated in numerous immunologic disorders, including multiple sclerosis (MS), inflammatory bowel disease, type 1 diabetes and rheumatoid arthritis3,4,5. In experimental autoimmune encephalomyelitis (EAE), a murine model for MS, altering the gut microbiome modulates central nervous system (CNS) autoimmunity. In a relapsing–remitting mouse model of spontaneous EAE, transgenic SJL/J mice raised in germ-free conditions were protected against developing the disease, while the introduction of commensal microbiota into the gut restored susceptibility6. While gnotobiotic mice are relatively immunocompromised due to lack of microbial stimulation promoting immune maturation, specific association of germ-free mice with defined commensal species has been shown to modulate the development and severity of EAE. Segmented-filamentous bacteria (SFB) drive expansion of Th17 cell populations and generation of interleukin (IL)-17 in the gut7. Mono-colonization of the gut of C57BL/6 mice with segmented-filamentous bacteria promotes Th17 accumulation in the spinal cords of mice and induces the development of EAE8. Conversely, treatment of C57BL/6 mice with a polysaccharide from the organism Bacteroides fragilis expands intestinal Foxp3+ CD4 Tregs and protects against the development of CNS autoimmunity9,10.
In the case of human autoimmune disease, associations have been reported with different members of the commensal microbiota. In a study of 20 MS patients versus 40 healthy controls, Faecalibacterium, Prevotella and Anaerostipes were decreased in MS, but the connection between microbiota, treatment and changes in immunity was not examined11. Prevotella copri has been associated in proinflammatory conditions, and has found to be enriched in patients with new-onset rheumatoid arthritis5, or capable of exacerbating dextran sodium sulfate colitis in antibiotic-treated C57BL/6 mice. Butyrate-producing organisms have protective associations with inflammatory conditions, for example, Faecalibacterium prausnitzii has been shown to be reduced in inflammatory bowel disease12. In neuromyelitis optica, a CNS autoimmune disease directed against aquaporin-4, there are increased antibodies against gastrointestinal antigens and cross-reactivity to a protein belonging to Clostridium perfringens, suggesting that autoimmunity in neuromyelitis optica may be driven by molecular mimicry against microbial antigens13. Similarly, the autoimmunity associated with Guillain–Barre syndrome has been associated with Campylobacter jejuni and the generation of antibodies to microbial components that cross-react with epitopes on the surface of the neuron14.
Given the importance of the gut microbiome in immune function and autoimmune disease, for the present work we investigated the human gut microbiome in multiple sclerosis (MS). We identify alterations in the intestinal microbiota and find correlations with MS-associated immune changes and treatment. If further studies demonstrate that these candidate microorganisms play an active role in either contributing to or ameliorating MS, then there is the potential to develop new diagnostics and therapies to combat the disease.
http://www.nature.com/articles/ncomms12015
Summary
In complex biological systems, small molecules often mediate microbe-microbe and microbe-host interactions. Using a systematic approach, we identified 3,118 small-molecule biosynthetic gene clusters (BGCs) in genomes of human-associated bacteria and studied their representation in 752 metagenomic samples from the NIH Human Microbiome Project. Remarkably, we discovered that BGCs for a class of antibiotics in clinical trials, thiopeptides, are widely distributed in genomes and metagenomes of the human microbiota. We purified and solved the structure of a thiopeptide antibiotic, lactocillin, from a prominent member of the vaginal microbiota. We demonstrate that lactocillin has potent antibacterial activity against a range of Gram-positive vaginal pathogens, and we show that lactocillin and other thiopeptide BGCs are expressed in vivo by analyzing human metatranscriptomic sequencing data. Our findings illustrate the widespread distribution of small-molecule-encoding BGCs in the human microbiome, and they demonstrate the bacterial production of drug-like molecules in humans.
ABSTRACT
OBJECTIVE: To determine if there are differences in the gut microbiome in MS and if changes occur with treatment. BACKGROUND: The gut microbiome plays a key role in shaping the immune repertoire and plays an important role in disease susceptibility in the EAE model. The gut microbiome has been described in other diseases but not yet in MS. DESIGNS/METHOD: MS patients from the Partners MS Center [untreated (n=22), glatiramer acetate treated (n=13), and IFN-b treated (n=18)] and healthy controls from the BWH PhenoGenetic project (n=44) were studied. Samples were profiled using two high throughput platforms (454 and Illumina 16s sequencing) to determine community structure and taxonomic composition of the gut microbome. RESULTS: We found an increase in Archaea (Methanobrevibacteriaceae) in MS vs. controls (p <0.00001 by 454 sequencing). Archaea are in a kingdom separate from bacteria and eukaryotes and in the human gut are dominated by Methanobrevibacter smithii, which make up 10% of colonic anaerobes in the gut. The cell wall and lipid membranes of M smithii make them strongly immunogenic consistent with a role in the induction of local and systemic inflammatory processes in the host. We also found two organisms with anti-inflammatory properties that were lower in MS vs. controls and which were increased with treatment. Specifically: 1) The Butyricimonas genus from Bacteroidetes phylum was lower in the untreated MS vs. controls. Butyricimonas are butyrate producers with anti-inflammatory effects; and 2) The Lachnospiraceae family from the Firmicutes phylum (which are also butyrate producers) was lower in untreated vs. treated MS irrespective of whether they were treated with IFN-β or glatiramer acetate. CONCLUSION: Our results identify changes in both pro-and anti-inflammatory epigenetic factors in the gut microbiome of MS subjects that may contribute to disease pathogenesis. Study supported by: NIH R21 and NMSS pilot grant.
Disclosure: Dr. Jhangi has nothing to disclose. Dr. Gandhi has nothing to disclose. Dr. Glanz has received research support from Merck Serono. Dr. Cook has nothing to disclose.
https://www.abovems.com/en_us/home/...randed-lifestyle-na-26312-unbranded_lifestyle
The gut microbiome and MS
Organisms that reside in the human gut—“the gut microbiome”—are being studied in MS. The full role of gut organisms in MS is not well understood. However, the gut’s role in helping “educate” the immune cells, its effect on inflammatory activity, and its role in other autoimmune disorders, has made it a new area of interest.
Remember, with so much information online, it’s important to be your own advocate. There are currently no specific medical guidelines about diet and MS. There is also no definitive evidence to suggest that diet or supplements alone affect the course of MS. It is important to work with your doctor to find the best nutritional plan for you and your MS.
Introduction
Microorganisms in the human gut encompass hundreds to thousands of bacterial, archaeal, viral and fungal species, making the human intestinal lumen a rich and dense source of antigenic diversity1. The gut mucosal immune system samples and processes these microbial antigens, potentially driving the expansion of particular immune subsets or generating specific immune repertoires2. Thus, the intestinal microbiome is an important entity within the host that influences immune responses both locally and systemically.
The gut microbiome has been implicated in numerous immunologic disorders, including multiple sclerosis (MS), inflammatory bowel disease, type 1 diabetes and rheumatoid arthritis3,4,5. In experimental autoimmune encephalomyelitis (EAE), a murine model for MS, altering the gut microbiome modulates central nervous system (CNS) autoimmunity. In a relapsing–remitting mouse model of spontaneous EAE, transgenic SJL/J mice raised in germ-free conditions were protected against developing the disease, while the introduction of commensal microbiota into the gut restored susceptibility6. While gnotobiotic mice are relatively immunocompromised due to lack of microbial stimulation promoting immune maturation, specific association of germ-free mice with defined commensal species has been shown to modulate the development and severity of EAE. Segmented-filamentous bacteria (SFB) drive expansion of Th17 cell populations and generation of interleukin (IL)-17 in the gut7. Mono-colonization of the gut of C57BL/6 mice with segmented-filamentous bacteria promotes Th17 accumulation in the spinal cords of mice and induces the development of EAE8. Conversely, treatment of C57BL/6 mice with a polysaccharide from the organism Bacteroides fragilis expands intestinal Foxp3+ CD4 Tregs and protects against the development of CNS autoimmunity9,10.
In the case of human autoimmune disease, associations have been reported with different members of the commensal microbiota. In a study of 20 MS patients versus 40 healthy controls, Faecalibacterium, Prevotella and Anaerostipes were decreased in MS, but the connection between microbiota, treatment and changes in immunity was not examined11. Prevotella copri has been associated in proinflammatory conditions, and has found to be enriched in patients with new-onset rheumatoid arthritis5, or capable of exacerbating dextran sodium sulfate colitis in antibiotic-treated C57BL/6 mice. Butyrate-producing organisms have protective associations with inflammatory conditions, for example, Faecalibacterium prausnitzii has been shown to be reduced in inflammatory bowel disease12. In neuromyelitis optica, a CNS autoimmune disease directed against aquaporin-4, there are increased antibodies against gastrointestinal antigens and cross-reactivity to a protein belonging to Clostridium perfringens, suggesting that autoimmunity in neuromyelitis optica may be driven by molecular mimicry against microbial antigens13. Similarly, the autoimmunity associated with Guillain–Barre syndrome has been associated with Campylobacter jejuni and the generation of antibodies to microbial components that cross-react with epitopes on the surface of the neuron14.
Given the importance of the gut microbiome in immune function and autoimmune disease, for the present work we investigated the human gut microbiome in multiple sclerosis (MS). We identify alterations in the intestinal microbiota and find correlations with MS-associated immune changes and treatment. If further studies demonstrate that these candidate microorganisms play an active role in either contributing to or ameliorating MS, then there is the potential to develop new diagnostics and therapies to combat the disease.
http://www.nature.com/articles/ncomms12015
Summary
In complex biological systems, small molecules often mediate microbe-microbe and microbe-host interactions. Using a systematic approach, we identified 3,118 small-molecule biosynthetic gene clusters (BGCs) in genomes of human-associated bacteria and studied their representation in 752 metagenomic samples from the NIH Human Microbiome Project. Remarkably, we discovered that BGCs for a class of antibiotics in clinical trials, thiopeptides, are widely distributed in genomes and metagenomes of the human microbiota. We purified and solved the structure of a thiopeptide antibiotic, lactocillin, from a prominent member of the vaginal microbiota. We demonstrate that lactocillin has potent antibacterial activity against a range of Gram-positive vaginal pathogens, and we show that lactocillin and other thiopeptide BGCs are expressed in vivo by analyzing human metatranscriptomic sequencing data. Our findings illustrate the widespread distribution of small-molecule-encoding BGCs in the human microbiome, and they demonstrate the bacterial production of drug-like molecules in humans.
ABSTRACT
OBJECTIVE: To determine if there are differences in the gut microbiome in MS and if changes occur with treatment. BACKGROUND: The gut microbiome plays a key role in shaping the immune repertoire and plays an important role in disease susceptibility in the EAE model. The gut microbiome has been described in other diseases but not yet in MS. DESIGNS/METHOD: MS patients from the Partners MS Center [untreated (n=22), glatiramer acetate treated (n=13), and IFN-b treated (n=18)] and healthy controls from the BWH PhenoGenetic project (n=44) were studied. Samples were profiled using two high throughput platforms (454 and Illumina 16s sequencing) to determine community structure and taxonomic composition of the gut microbome. RESULTS: We found an increase in Archaea (Methanobrevibacteriaceae) in MS vs. controls (p <0.00001 by 454 sequencing). Archaea are in a kingdom separate from bacteria and eukaryotes and in the human gut are dominated by Methanobrevibacter smithii, which make up 10% of colonic anaerobes in the gut. The cell wall and lipid membranes of M smithii make them strongly immunogenic consistent with a role in the induction of local and systemic inflammatory processes in the host. We also found two organisms with anti-inflammatory properties that were lower in MS vs. controls and which were increased with treatment. Specifically: 1) The Butyricimonas genus from Bacteroidetes phylum was lower in the untreated MS vs. controls. Butyricimonas are butyrate producers with anti-inflammatory effects; and 2) The Lachnospiraceae family from the Firmicutes phylum (which are also butyrate producers) was lower in untreated vs. treated MS irrespective of whether they were treated with IFN-β or glatiramer acetate. CONCLUSION: Our results identify changes in both pro-and anti-inflammatory epigenetic factors in the gut microbiome of MS subjects that may contribute to disease pathogenesis. Study supported by: NIH R21 and NMSS pilot grant.
Disclosure: Dr. Jhangi has nothing to disclose. Dr. Gandhi has nothing to disclose. Dr. Glanz has received research support from Merck Serono. Dr. Cook has nothing to disclose.
https://www.abovems.com/en_us/home/...randed-lifestyle-na-26312-unbranded_lifestyle
The gut microbiome and MS
Organisms that reside in the human gut—“the gut microbiome”—are being studied in MS. The full role of gut organisms in MS is not well understood. However, the gut’s role in helping “educate” the immune cells, its effect on inflammatory activity, and its role in other autoimmune disorders, has made it a new area of interest.
Remember, with so much information online, it’s important to be your own advocate. There are currently no specific medical guidelines about diet and MS. There is also no definitive evidence to suggest that diet or supplements alone affect the course of MS. It is important to work with your doctor to find the best nutritional plan for you and your MS.
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