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#living with lupus#lupus symptoms#chronic inflammation#autoimmune#gut microbiome#ruminococcus gnavus
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The gut microbiota and tumor-associated macrophages (TAMs) affect tumor responses to anti–programmed cell death protein 1 (PD-1) immune checkpoint blockade. Reprogramming TAM by either blocking or deleting the macrophage receptor triggering receptor on myeloid cells 2 (TREM2) attenuates tumor growth, and lack of functional TREM2 enhances tumor elimination by anti–PD-1. Here, we found that anti–PD-1 treatment combined with TREM2 deficiency in mice induces proinflammatory programs in intestinal macrophages and a concomitant expansion of Ruminococcus gnavus in the gut microbiota. Gavage of wild-type mice with R. gnavus enhanced anti–PD-1–mediated tumor elimination, recapitulating the effect occurring in the absence of TREM2. A proinflammatory intestinal environment coincided with expansion, increased circulation, and migration of TNF-producing CD4+ T cells to the tumor bed. Thus, TREM2 remotely controls anti–PD-1 immune checkpoint blockade through modulation of the intestinal immune environment and microbiota, with R. gnavus emerging as a potential probiotic agent for increasing responsiveness to anti-PD-1.
TREM2 deficiency reprograms intestinal macrophages and microbiota to enhance anti–PD-1 tumor immunotherapy | Science Immunology
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Comparative genomics reveals extensive intra-species genetic divergence of the prevalent gut commensal Ruminococcus gnavus
http://dlvr.it/SsvxRV
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Letter to the Editor
Faecalibacterium prausnitzii over ASVs related to species in the genus Bacteroides (B. dorei, B. massiliensis and B. thetaiotaomicron) (figure 1E), which provided an area under the curve (AUC) of 0.863 for differentiating individuals with PASC from RC. Balance values also negatively correlated with IL-6 (r=−0.44, p=0.01). These microbiome differences are consistent with Liu et al,1 who also reported higher levels of Bacteroides (B. vulgatus specifically) and lower F. prausnitzii with PASC. Liu et al also reported higher Ruminococcus gnavus with PASC, and lower Collinsella aerofaciens, and Blautia obeum. Interestingly, an ASV highly related to R. gnavus (100% identity over V4 read) correlated positively with IL-6 and ASVs related to F. prausnitzii (98.7% ID), C. aerofaciens (100% ID) and B. obeum (100% ID) all negatively correlated with IL-6 and/or CRP levels in our study
A mechanistic link between microbiome differences and high inflammation in PASC is supported by studies showing anti-inflammatory effects of F. prausnitzii5 and proinflammatory effects of R. gnavus.6 Higher levels of particular Bacteroides and R. gnavus in PASC may also be interesting because R. gnavus, B. thetaiotaomicron and B. vulgatus all produce sialidases that can liberate sialic acids from host mucin.7–9 B. thetaiotaomicron can also increase the ratio of sialylated to sulfated mucins in mono-associated rats, and this effect was diminished by co-colonisation with F. prausnitzii.10 Sialic acids may be important in SARS-CoV-2 pathogenesis because the receptor-binding domain of the spike protein recognises sialic acid-containing oligosaccharides.11 Increased levels of microbially liberated sialic acids could support immune evasion by SARS-CoV-2 when free sialic acids bind to the spike protein; sialic acids are used for host immune evasion by multiple bacterial pathogens.12 Sialidase and sialyltransferase inhibitors have been effective in influenza prophylaxis and symptom relief,13 and also prevented pathogen outgrowth due to liberation of sialic acids from gut mucins by B. vulgatus in mice8, suggesting that, if experimentally validated, sialidase inhibition has therapeutic potential for PASC.
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2017 Study: The Gut Microbiome In Cardiovascular Disease https://go.nature.com/2GOeXPS 🤓 Scientists compared a group of 218 people with cardiovascular disease (CVD) with a control group of 187 healthy folk🔬 Among their findings was that CVD group had more Ruminococcus gnavus, a bacterium previously associated with inflammatory bowel diseases (Crohn's and colitis) and low microbial richness - which tends to be a marker of an unhappy microbiome! 😯💩🤨 #gut #guthealth #healthygut #microbiome #weightloss #mentalhealth #autoimmune #gaps #gapsdiet #paleo #paleodiet #fodmap #glutenfree #whole30 #keto #ketodiet #detox #clean #cleaneating #cleaneats #organic #organicfood #mealprep #wellness #supplements #intermittentfasting #heart #hearthealth #hearthealthy #guthealing
#wellness#gut#guthealing#supplements#mealprep#healthygut#glutenfree#heart#hearthealth#whole30#keto#mentalhealth#organic#paleo#cleaneating#hearthealthy#autoimmune#gaps#intermittentfasting#detox#clean#paleodiet#microbiome#weightloss#fodmap#cleaneats#guthealth#organicfood#ketodiet#gapsdiet
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Las erupciones de #lupus pueden estar asociadas con el aumento de una #bacteria específica intestinal. El reciente trabajo realizado en sesenta mujeres enfermas de #lupus permitió estudiar la particularidad de su microbiota intestinal. Los resultados confirman que las fases de desequilibrio de la microbiota coinciden con las fases de actividad de la enfermedad. La bacteria responsable: #Ruminococcus gnavus Los investigadores consiguieron identificar una bacteria, Ruminococcus gnavus, cuya superabundancia muestra una correlación positiva con la actividad de la enfermedad. Este desequilibrio va acompañado de una alteración de la barrera intestinal, que aumentaría la exposición del sistema inmunitario a las bacterias digestivas, algunas de ellas patógenas. www.microbiotico.com 01 (81) 8850-7840 y 41 (en Dr. Christian Cornejo - Restaurart.mx) https://www.instagram.com/p/Bx43wgzgD0m/?igshid=8tkfsseonvog
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researchers at Washington University School of Medicine in St. Louis have found, in mice, that a strain of gut bacteria—Ruminococcus gnavus—can enhance the effects of cancer immunotherapy.
Gut bacteria enhance cancer immunotherapy in mouse study
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Gut microbiome of patients with PACS were characterised by higher levels of Ruminococcus gnavus, Bacteroides vulgatus and lower levels of Faecalibacterium prausnitzii. Persistent respiratory symptoms were correlated with opportunistic gut pathogens, and neuropsychiatric symptoms and fatigue were correlated with nosocomial gut pathogens, including Clostridium innocuum and Actinomyces naeslundii. Butyrate-producing bacteria, including Bifidobacterium pseudocatenulatum and Faecalibacterium prausnitzii showed the largest inverse correlations with PACS at 6 months.
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Effetti benefici della Dieta Mediterranea in soggetti sovrappeso e obesi
Studio europeo coordinato dall'Università degli Studi di Napoli Federico II Effetti benefici della Dieta Mediterranea in soggetti sovrappeso e obesi. Li dimostra uno studio europeo, coordinato dall'Università degli Studi di Napoli Federico II, in collaborazione con l'Università di Copenaghen e l'istituto francese MetaGenoPolis. Effetti benefici di un intervento nutrizionale con la Dieta Mediterranea sulla composizione e sulle funzionalità del microbioma intestinale, sul metaboloma sistemico e sui livelli di colesterolo in una popolazione sovrappeso a rischio di sviluppo di malattie cardiovascolari. Li dimostra uno studio europeo, coordinato dall'Università degli Studi di Napoli Federico II, in collaborazione con l'Università di Copenaghen e l'istituto francese MetaGenoPolis. La ricerca, appena pubblicata sulla prestigiosa rivista scientifica Gut, evidenzia come esista un rapporto diretto tra l'alimentazione, il microbioma intestinale e la salute dell'uomo. I partner del progetto europeo DINAMIC - Diet-induced Arrangement of the gut Microbiome for Improvement of Cardiometabolic health - hanno condotto uno studio di intervento nutrizionale randomizzato controllato di 8 settimane in soggetti sovrappeso e obesi con uno stile di vita sedentario. I risultati mostrano chiaramente che un cambiamento nel comportamento alimentare, senza alcuna concomitante modifica dell'apporto energetico individuale dell'assunzione di macronutrienti e dell'attività fisica, può ridurre i livelli ematici di colesterolo, già dopo 4 settimane, in una popolazione a elevato rischio cardio-metabolico per uno scorretto stile di vita. Inoltre, una maggiore aderenza alla dieta mediterranea induce cambiamenti del microbioma intestinale e della sua funzionalità, importanti per la salute umana. In linea con gli aspetti legati alla nutrizione personalizzata, i dati mostrano che alcuni individui ospitano un microbioma intestinale che è più suscettibile ai cambiamenti indotti dalla dieta mediterranea e vanno incontro ad ulteriori vantaggi clinici come il miglioramento della sensibilità all'insulina e dello stato infiammatorio. Il team multidisciplinare ha visto protagonisti i gruppi di ricerca dei docenti Danilo Ercolini, Paola Vitaglione e Angela Rivellese della Task Force della Federico II per gli Studi sul Microbioma; Lars O. Dragsted ed Henrik M. Roager del Dipartimento di Nutrizione, Esercizio e Sport dell'Università di Copenaghen, e i membri del gruppo di ricerca dell'istituto di ricerca francese MetaGenoPolis (INRAE) dell'Università di Parigi-Saclay coordinato da Dusko S. Ehrlich. Analizzato, quindi, l'effetto della dieta mediterranea sulla composizione del microbioma intestinale e su parametri clinici, metabolici e antropometrici di 82 soggetti sani, sovrappeso ed obesi, a rischio di sviluppo di malattie cardiovascolari. I partecipanti sono stati inclusi nel gruppo di intervento con dieta mediterranea (n=43) o nel gruppo di controllo (n=39). I partecipanti nel gruppo con dieta mediterranea hanno ricevuto un piano dietetico individuale sul modello mediterraneo, equivalente a quello abituale per calorie e composizione in macronutrienti. Quindi questi volontari hanno aumentato l'introito di fibra alimentare, proteine vegetali e grassi insaturi e hanno ridotto carboidrati semplici, proteine animali e grassi saturi. I volontari nel gruppo di controllo non hanno modificato le proprie abitudini alimentari per la durata dello studio. Tutti i volontari hanno mantenuto lo stile di vita sedentario durante il periodo di intervento. Dall'analisi dei dati di metagenomica, analisi dei genomi di tutti i componenti del microbioma intestinale, e metabolomica, analisi dei metaboliti, è stato definito il profilo del microbioma e del metaboloma della popolazione in studio contestualmente ai dati clinici e antropometrici. Dopo 4 settimane i volontari che consumavano una dieta mediterranea hanno mostrato una riduzione del colesterolo plasmatico totale rispetto ai controlli. Inoltre, i volontari che hanno aumentato maggiormente l'aderenza alla MD hanno anche mostrato un aumento dei batteri che degradano le fibre e che producono acidi grassi a corta catena, come alcuni ceppi di Faecalibacterium prausnitzii, un arricchimento nei pathways di degradazione di trigliceridi del metabolismo del butirrato e una diminuzione delle specie potenzialmente pro-infiammatorie, es. Ruminococcus gnavus. L'aderenza alla dieta mediterranea è stata dimostrata con un aumento dei markers di consumo degli alimenti di origine vegetale e una diminuzione di quelli di alimenti di origine animale quali minori livelli plasmatici e urinari di carnitina e prodotti di degradazione delle proteine animali. Per quanto riguarda i metaboliti microbici di interesse salutistico e legati alla dieta, è stato evidenziato un aumento nelle urine dei livelli di urolitine, molecole dalle proprietà antiinfiammatorie prodotte dal microbiota intestinale a partire da polifenoli presenti nelle noci. Infine, è stata osservata una riduzione della produzione di acidi biliari fecali e della resistenza all'insulina, e tali cambiamenti erano correlati ai livelli basali e alle variazioni delle specie microbiche coinvolte in queste specifiche caratteristiche metaboliche. Read the full article
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Diets enriched with cranberry beans alter the microbiota and mitigate colitis severity and associated inflammation.
PMID: J Nutr Biochem. 2016 Feb ;28:129-39. Epub 2015 Nov 4. PMID: 26878790 Abstract Title: Diets enriched with cranberry beans alter the microbiota and mitigate colitis severity and associated inflammation. Abstract: Common beans are rich in phenolic compounds and nondigestible fermentable components, which may help alleviate intestinal diseases. We assessed the gut health priming effect of a 20% cranberry bean flour diet from two bean varieties with differing profiles of phenolic compounds [darkening (DC) and nondarkening (NDC) cranberry beans vs. basal diet control (BD)] on critical aspects of gut health in unchallenged mice, and during dextran sodium sulfate (DSS)-induced colitis (2% DSS wt/vol, 7 days). In unchallenged mice, NDC and DC increased (i) cecal short-chain fatty acids, (ii) colon crypt height, (iii) crypt goblet cell number and mucus content and (iv) Muc1, Klf4, Relmβ and Reg3γ gene expression vs. BD, indicative of enhanced microbial activity and gut barrier function. Fecal 16S rRNA sequencing determined that beans reduced abundance of the Lactobacillaceae (Ruminococcus gnavus), Clostridiaceae (Clostridium perfringens), Peptococcaceae, Peptostreptococcaceae,Rikenellaceae and Pophyromonadaceae families, and increased abundance of S24-7 and Prevotellaceae. During colitis, beans reduced (i) disease severity and colonic histological damage, (ii) increased gene expression of barrier function promoting genes (Muc1-3, Relmβ, and Reg3γ) and (iii) reduced colonic and circulating inflammatory cytokines (IL-1β, IL-6, IFNγ and TNFα). Therefore, prior to disease induction, bean supplementation enhanced multiple concurrent gut health promoting parameters that translated into reduced colitis severity. Moreover, both bean diets exerted similar effects, indicating that differing phenolic content did not influence the endpoints assessed. These data demonstrate a proof-of-concept regarding the gut-priming potential of beans in colitis, which could be extended to mitigate the severity of other gut barrier-associated pathologies.
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Using recent gene flow to define microbe populations
Identifying species among plants and animals has been a full-time occupation for some biologists, but the task is even more daunting for the myriad microbes that inhabit the planet. Now, MIT researchers have developed a simple measurement of gene flow that can define ecologically important populations among bacteria and archaea, including pinpointing populations associated with human diseases.
The gene flow metric separates co-existing microbes in genetically and ecologically distinct populations, Martin Polz, a professor of civil and environmental engineering at MIT, and colleagues write in the August 8 issue of Cell.
Polz and his colleagues also developed a method to identify parts of the genome in these populations that show different adaptations that can be mapped onto different environments. When they tested their approach on a gut bacterium, for instance, they were able to determine that different populations of the bacteria were associated with healthy individuals and patients with Crohn’s disease.
Biologists often call a group of plants or animals a species if the group is reproductively isolated from others — that is, individuals in the group can reproduce with each other, but they can’t reproduce with others. As a result, members of a species share a set of genes that differs from other species. Much of evolutionary theory centers on species and populations, the representatives of a species in a particular area.
But microbes “defy the classic species concept for plants and animals,” Polz explains. Microbes tend to reproduce asexually, simply splitting themselves in two rather than combining their genes with other individuals to produce offspring. Microbes are also notorious for “taking up DNA from environmental sources, such as viruses,” he says. “Viruses can transfer DNA into microbial cells and that DNA can be incorporated into their genomes.”
These processes make it difficult to sort coexisting microbes into distinct populations based on their genetic makeup. “If we can’t identify those populations in microbes, we can’t one-to-one apply all this rich ecological and evolutionary theory that has been developed for plants and animals to microbes,” says Polz.
If researchers want to measure an ecosystem’s resilience in the face of environmental change, for instance, they might look at how populations within species change over time. “If we don’t know what a species is, it’s very difficult to measure and assess these types of perturbations,” he adds.
Christopher Marx, a microbiologist at the University of Idaho who was not part of the Cell study, says he and his colleagues “will immediately apply” the MIT researchers’ approach to their own work. “We can use this to answer the question, ‘What should we define as an ecologically important unit?’”
A yardstick for gene flow
Martin and his colleagues decided to look for another way to define ecologically meaningful populations in microbes. Led by microbiology graduate student Philip Arevalo, the researchers developed a metric of gene flow that they called PopCOGenT (Populations as Clusters Of Gene Transfer).
PopCOGenT measures recent gene flow or gene transfer between closely related genomes. In general, microbial genomes that have exchanged DNA recently should share longer and more frequent stretches of identical DNA than if individuals were just reproducing by splitting their DNA in two. Without this sort of recent exchange, the researchers suggested, the length of these shared stretches of identical DNA would shorten as mutations insert new “letters” into the stretch.
Two microbial strains that are not genetically identical to each other but share sizable “chunks” of identical DNA are probably exchanging more genetic material with each other than with other strains. This gene flow measurement can define distinct microbial populations, as the researchers discovered in their tests of three different kinds of bacteria.
In Vibrio bacteria, for instance, closely related populations may share some core gene sequences, but they appear completely isolated from each other when viewed through this measurement of recent gene flow, Polz and colleagues found.
Polz says that the PopCOGenT method may work better at defining microbial populations than previous studies because it focuses on recent gene flow among closely related organisms, rather than including gene flow events that may have happened thousands of years in the past.
The method also suggests that while microbes are constantly taking in different DNA from their environment that might obscure patterns of gene flow, “it may be that this divergent DNA is really removed by selection from populations very quickly,” says Polz.
The reverse ecology approach
Microbiology graduate student David VanInsberghe then suggested a “reverse ecology” approach that could identify regions of the genome in these newly defined populations that show “selective sweeps” — places where DNA variation is reduced or eliminated, likely as a result of strong natural selection for a particular beneficial genetic variant.
By identifying specific sweeps within populations, and mapping the distribution of these populations, the method can reveal possible adaptations that drive microbes to inhabit a particular environment or host — without any prior knowledge of their environment. When the researchers tested this approach in the gut bacterium Ruminococcus gnavus, they uncovered separate populations of the microbe associated with healthy people and patients with Crohn’s disease.
Polz says the reverse ecology method is likely to be applied in the near future to studying the full diversity of the bacteria that inhabit the human body. “There is a lot of interest in sequencing closely related organisms within the human microbiome and looking for health and disease associations, and the datasets are growing.”
He hopes to use the approach to examine the “flexible genome” of microbes. Strains of E. coli bacteria, for instance, share about 40 percent of their genes in a “core genome,” while the other 60 percent — the flexible part — varies between strains. “For me, it’s one of the biggest questions in microbiology: Why are these genomes so diverse in gene content?” Polz explains. “Once we can define populations as evolutionary units, we can interpret gene frequencies in these populations in light of evolutionary processes.”
Polz and colleagues’ findings could increase estimates of microbe diversity, says Marx. “What I think is really cool about this approach from Martin’s group is that they actually suggest that the complexity that we see is even more complex than we’re giving it credit for. There may be even more types that are ecologically important out there, things that if they were plants and animals we would be calling them species.”
Other MIT authors on the paper include Joseph Elsherbini and Jeff Gore. The research was supported, in part, by the National Science Foundation and the Simons Foundation.
Using recent gene flow to define microbe populations syndicated from https://osmowaterfilters.blogspot.com/
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Gut bacteria release a polysaccharide that triggers an immune response in Chohn’s disease
The culprit - a bacteria Ruminococcus gnavus. The population of this bacteria is elevated in by 50% in those who have Chrohn’s disease. This study looked at the bacteria in culture and provides a molecular mechanism to explain Chrohn’s disease.
Matthew T. Henke et al. Ruminococcus gnavus, a member of the human gut microbiome associated with Crohn's disease, produces an inflammatory polysaccharide, Proceedings of the National Academy of Sciences (2019). DOI: 10.1073/pnas.1904099116
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Disorganized Gut Microbiome Contributed to Liver Cirrhosis Progression: A Meta-Omics-Based Study.
Related Articles Disorganized Gut Microbiome Contributed to Liver Cirrhosis Progression: A Meta-Omics-Based Study. Front Microbiol. 2018;9:3166 Authors: Shao L, Ling Z, Chen D, Liu Y, Yang F, Li L Abstract Early detection and effective interventions for liver cirrhosis (LC) remain an urgent unmet clinical need. Inspired from intestinal disorders in LC patients, we investigated the associations between gut microbiome and disease progression based on a raw metagenomic dataset of 47 healthy controls, 49 compensated, and 46 decompensated LC patients from our previous study, and a metabolomic dataset of urine samples from the same controls/patients using ultra-performance liquid chromatography/mass spectrophotometry system. It was found that the combination and relative abundance of gut microbiome, the inter-microbiome regulatory networks, and the microbiome-host correlation patterns varied during disease progression. The significant reduction of bacteria involved in fermentation of plant cell wall polysaccharides and resistant starch (such as Alistipes sp. HG5, Clostridium thermocellum) contributed to the reduced supply of energy sources, the disorganized self-feeding and cross-feeding networks and the thriving of some opportunistic pathogens in genus Veillonella. The marked decrease of butyrate-producing bacteria and increase of Ruminococcus gnavus implicated in degradation of elements from the mucus layer provided an explanation for the impaired intestinal barrier function and systematic inflammation in LC patients. Our results pave the way for further developments in early detection and intervention of LC targeting on gut microbiome. PMID: 30631318 [PubMed] http://dlvr.it/Qwcw2C
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