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1.
Nat Commun ; 11(1): 5773, 2020 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-33188211

RESUMO

Beneficial modulation of the gut microbiome has high-impact implications not only in humans, but also in livestock that sustain our current societal needs. In this context, we have tailored an acetylated galactoglucomannan (AcGGM) fibre to match unique enzymatic capabilities of Roseburia and Faecalibacterium species, both renowned butyrate-producing gut commensals. Here, we test the accuracy of AcGGM within the complex endogenous gut microbiome of pigs, wherein we resolve 355 metagenome-assembled genomes together with quantitative metaproteomes. In AcGGM-fed pigs, both target populations differentially express AcGGM-specific polysaccharide utilization loci, including novel, mannan-specific esterases that are critical to its deconstruction. However, AcGGM-inclusion also manifests a "butterfly effect", whereby numerous metabolic changes and interdependent cross-feeding pathways occur in neighboring non-mannanolytic populations that produce short-chain fatty acids. Our findings show how intricate structural features and acetylation patterns of dietary fibre can be customized to specific bacterial populations, with potential to create greater modulatory effects at large.


Assuntos
Fibras na Dieta/farmacologia , Microbioma Gastrointestinal , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologia , Metabolismo Secundário , Acetilação/efeitos dos fármacos , Animais , Butiratos/metabolismo , Ceco/metabolismo , Dieta , Comportamento Alimentar/efeitos dos fármacos , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/efeitos dos fármacos , Genoma , Masculino , Mananas/farmacologia , Redes e Vias Metabólicas/efeitos dos fármacos , Metagenômica , Análise de Componente Principal , Proteoma/metabolismo , RNA Ribossômico 16S/genética , Metabolismo Secundário/efeitos dos fármacos , Suínos , Madeira/química
2.
Nat Commun ; 11(1): 4457, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32901017

RESUMO

Innate lymphoid cells (ILCs) and CD4+ T cells produce IL-22, which is critical for intestinal immunity. The microbiota is central to IL-22 production in the intestines; however, the factors that regulate IL-22 production by CD4+ T cells and ILCs are not clear. Here, we show that microbiota-derived short-chain fatty acids (SCFAs) promote IL-22 production by CD4+ T cells and ILCs through G-protein receptor 41 (GPR41) and inhibiting histone deacetylase (HDAC). SCFAs upregulate IL-22 production by promoting aryl hydrocarbon receptor (AhR) and hypoxia-inducible factor 1α (HIF1α) expression, which are differentially regulated by mTOR and Stat3. HIF1α binds directly to the Il22 promoter, and SCFAs increase HIF1α binding to the Il22 promoter through histone modification. SCFA supplementation enhances IL-22 production, which protects intestines from inflammation. SCFAs promote human CD4+ T cell IL-22 production. These findings establish the roles of SCFAs in inducing IL-22 production in CD4+ T cells and ILCs to maintain intestinal homeostasis.


Assuntos
Ácidos Graxos Voláteis/imunologia , Microbioma Gastrointestinal/imunologia , Imunidade Inata , Interleucinas/biossíntese , Animais , Butiratos/imunologia , Butiratos/metabolismo , Butiratos/farmacologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/microbiologia , Citrobacter rodentium , Colite/imunologia , Colite/microbiologia , Colite/prevenção & controle , Infecções por Enterobacteriaceae/imunologia , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/prevenção & controle , Ácidos Graxos Voláteis/metabolismo , Ácidos Graxos Voláteis/farmacologia , Microbioma Gastrointestinal/fisiologia , Inibidores de Histona Desacetilases/farmacologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Técnicas In Vitro , Interleucinas/deficiência , Interleucinas/genética , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Linfócitos/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Regiões Promotoras Genéticas , Receptores de Hidrocarboneto Arílico/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo
3.
Nat Commun ; 11(1): 4659, 2020 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-32938936

RESUMO

The αvß6 integrin plays a key role in the activation of transforming growth factor-ß (TGFß), a pro-fibrotic mediator that is pivotal to the development of idiopathic pulmonary fibrosis (IPF). We identified a selective small molecule αvß6 RGD-mimetic, GSK3008348, and profiled it in a range of disease relevant pre-clinical systems. To understand the relationship between target engagement and inhibition of fibrosis, we measured pharmacodynamic and disease-related end points. Here, we report, GSK3008348 binds to αvß6 with high affinity in human IPF lung and reduces downstream pro-fibrotic TGFß signaling to normal levels. In human lung epithelial cells, GSK3008348 induces rapid internalization and lysosomal degradation of the αvß6 integrin. In the murine bleomycin-induced lung fibrosis model, GSK3008348 engages αvß6, induces prolonged inhibition of TGFß signaling and reduces lung collagen deposition and serum C3M, a marker of IPF disease progression. These studies highlight the potential of inhaled GSK3008348 as an anti-fibrotic therapy.


Assuntos
Butiratos/farmacologia , Fibrose Pulmonar Idiopática/tratamento farmacológico , Integrinas/antagonistas & inibidores , Naftiridinas/farmacologia , Pirazóis/farmacologia , Pirrolidinas/farmacologia , Administração por Inalação , Animais , Antígenos de Neoplasias/metabolismo , Bleomicina/toxicidade , Butiratos/administração & dosagem , Butiratos/metabolismo , Butiratos/farmacocinética , Colágeno/metabolismo , Modelos Animais de Doenças , Células Epiteliais/efeitos dos fármacos , Humanos , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/patologia , Integrinas/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Naftiridinas/administração & dosagem , Naftiridinas/metabolismo , Naftiridinas/farmacocinética , Pirazóis/administração & dosagem , Pirazóis/metabolismo , Pirazóis/farmacocinética , Pirrolidinas/administração & dosagem , Pirrolidinas/metabolismo , Pirrolidinas/farmacocinética , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Tomografia Computadorizada de Emissão de Fóton Único , Fator de Crescimento Transformador beta/metabolismo , Pesquisa Médica Translacional
4.
J Oleo Sci ; 69(9): 1077-1085, 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32788520

RESUMO

There is growing research interest in the hypocholesterolemic effect of various food components such as polyphenols. In this study, we examined the effects of oligonol-a low-molecular weight polyphenol extracted from lychee fruit-on cholesterol metabolism in rats under short-term administration. Administration of oligonol for 3 days significantly increased cecum weight and decreased cecal n-butyric acid concentrations in rats. Oligonol also significantly lowered the levels of hepatic cholesterol and increased the levels of total neutral steroids excreted in the feces. It also increased fecal ß-muricholic acid significantly, whereas the levels of total acidic steroids remained unchanged. Gene expression of hepatic CYP7A1 (cytochrome P450 family 7 subfamily A member 1) significantly increased following the administration of oligonol. This increase could be ascribed to changes in the expression of farnesoid X receptor, small heterodimer partner, and fibroblast growth factor 15 in ileum. Our data suggest that oligonol induces hypocholesterolemic effects through the inhibition of biliary cholesterol absorption from the intestine and the upregulation of cholesterol catabolism in rats even following short-term administration. Therefore, oligonol may be an important food component for reducing cholesterol level.


Assuntos
Catequina/análogos & derivados , Colesterol/metabolismo , Litchi/química , Fenóis/isolamento & purificação , Fenóis/farmacologia , Animais , Butiratos/metabolismo , Catequina/administração & dosagem , Catequina/isolamento & purificação , Catequina/farmacologia , Colesterol 7-alfa-Hidroxilase/genética , Colesterol 7-alfa-Hidroxilase/metabolismo , Expressão Gênica/efeitos dos fármacos , Íleo/metabolismo , Fígado/metabolismo , Masculino , Peso Molecular , Fenóis/administração & dosagem , Polifenóis , Ratos Wistar , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Fatores de Tempo
5.
Appl Environ Microbiol ; 86(21)2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-32859598

RESUMO

Whole grains are generally low in nondigestible carbohydrates that are available for fermentation by the gut microbiota, or microbiota-accessible carbohydrates (MAC). However, there is potential to increase MAC in whole grains through food processing. Five processing methods: boiling, extrusion, sourdough bread, unleavened bread, and yeast bread, were applied to whole wheat flour and then subjected to in vitro digestion followed by fermentation using fecal microbiomes from 10 subjects. The microbiomes separated into 2 groups: those that showed high carbohydrate utilization (CU) and those that exhibited low CU. The former exhibited not only enhanced CU but also increased butyrate production (MAC, 31.1 ± 1.1% versus 19.3 ± 1.2%, P < 0.001; butyrate, 5.26 ± 0.26 mM versus 3.17 ± 0.27 mM, P < 0.001). Only the microbiomes in the high-CU group showed significant differences among processing methods: extrusion and sourdough bread led to dichotomous results for MAC and short-chain fatty acid production, where extrusion resulted in high MAC but low butyrate production while sourdough bread resulted in low MAC but high butyrate production. Extrusion led to a noticeable decrease in α-diversity and some members of the families Ruminococcaceae and Lachnospiraceae, with increases in Acinetobacter, Enterococcus, and Staphylococcaceae This study demonstrated that only microbiomes that exhibited high CU responded to the effects of processing by showing significant differences among processing methods. In these microbiomes, extrusion was able to increase accessibility of the cell wall polysaccharides but did not increase butyrate production. In contrast, sourdough bread led to high butyrate production by supporting important butyrate-producers in the families Lachnospiraceae and Ruminococcaceae IMPORTANCE Dietary nondigestible carbohydrates, or dietary fiber, have long been recognized for their beneficial health effects. However, recent studies have revealed that fermentation of nondigestible carbohydrates by gut bacteria is critical in mediating many of the health-promoting properties of dietary fibers. Whole grains are excellent candidates to supply the microbiome with a plentiful source of nondigestible carbohydrates, although unfortunately a majority of these carbohydrates in whole grains are not available to gut bacteria for fermentation. Processing is known to alter the structural characteristics of nondigestible carbohydrates in whole grains, yet the relationship between these effects and gut microbial fermentation is unknown. This research aimed to address this important research gap by identifying interactions between whole-grain processing and gut bacteria, with the ultimate goal of increasing the availability of nondigestible carbohydrates for fermentation to enhance host health.


Assuntos
Bactérias/isolamento & purificação , Metabolismo dos Carboidratos , Fermentação , Farinha , Manipulação de Alimentos/métodos , Microbiota , Grãos Integrais/química , Butiratos/metabolismo , Triticum
6.
Nat Commun ; 11(1): 3285, 2020 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-32620774

RESUMO

The early life human gut microbiota exerts life-long health effects on the host, but the mechanisms underpinning its assembly remain elusive. Particularly, the early colonization of Clostridiales from the Roseburia-Eubacterium group, associated with protection from colorectal cancer, immune- and metabolic disorders is enigmatic. Here, we describe catabolic pathways that support the growth of Roseburia and Eubacterium members on distinct human milk oligosaccharides (HMOs). The HMO pathways, which include enzymes with a previously unknown structural fold and specificity, were upregulated together with additional glycan-utilization loci during growth on selected HMOs and in co-cultures with Akkermansia muciniphila on mucin, suggesting an additional role in enabling cross-feeding and access to mucin O-glycans. Analyses of 4599 Roseburia genomes underscored the preponderance and diversity of the HMO utilization loci within the genus. The catabolism of HMOs by butyrate-producing Clostridiales may contribute to the competitiveness of this group during the weaning-triggered maturation of the microbiota.


Assuntos
Butiratos/metabolismo , Clostridiales/metabolismo , Leite Humano/metabolismo , Mucinas/metabolismo , Oligossacarídeos/metabolismo , Bifidobacterium/metabolismo , Clostridiales/genética , Colo/microbiologia , Eubacterium/metabolismo , Microbioma Gastrointestinal/fisiologia , Humanos , Lactente , Recém-Nascido , Metabolismo/fisiologia , Leite Humano/química , Polissacarídeos/metabolismo , Verrucomicrobia/metabolismo , Desmame
7.
PLoS One ; 15(6): e0232831, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32497096

RESUMO

The burden of enteric pathogens in poultry is growing after the ban of antibiotic use in animal production. Organic acids gained attention as a possible alternative to antibiotics due to their antimicrobial activities, improved nutrient metabolism and performance. The current study was conducted to evaluate the effectiveness of organic acid blend on broilers cecal microbiota, histomorphometric measurements, and short-chain fatty acid production in Salmonella enterica serovar Typhimurium challenge model. Birds were divided into four treatments, including a negative control, positive control challenged with S. Typhimurium, group supplemented with an organic acid blend, and birds supplemented with organic acid blend and Salmonella challenged. Results illustrate significant differences in feed conversion ratios and production efficiency factor between treatment groups, however, the influence of organic acid supplement was marginal. Organic acid blend significantly increased cecal acetic and butyric acids concentrations when compared to unsupplemented groups and resulted in minor alterations of intestinal bacterial communities.


Assuntos
Acetatos/metabolismo , Ração Animal , Butiratos/metabolismo , Galinhas/microbiologia , Suplementos Nutricionais , Ácidos Graxos/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Doenças das Aves Domésticas/terapia , Salmonelose Animal/terapia , Salmonella typhimurium/efeitos dos fármacos , Animais , Ceco/microbiologia , Galinhas/metabolismo , Ácidos Graxos/administração & dosagem , Ácidos Graxos Voláteis/administração & dosagem , Ácidos Graxos Voláteis/farmacologia , Íleo/metabolismo , Íleo/ultraestrutura , Mananas/administração & dosagem , Microvilosidades/ultraestrutura , Doenças das Aves Domésticas/microbiologia , Doenças das Aves Domésticas/prevenção & controle , Distribuição Aleatória , Salmonelose Animal/microbiologia , Salmonelose Animal/prevenção & controle , Salmonella typhimurium/isolamento & purificação , Salmonella typhimurium/metabolismo
8.
Sci Rep ; 10(1): 8516, 2020 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-32444846

RESUMO

The ketone body D-ß-hydroxybutyrate (DBHB) has gained attention owing to its cellular signalling function; however, its effect on the human colonic microbiota remains unclear. Here, DBHB dynamics in the human colon were investigated using an in vitro colonic microbiota model, which maintained most of the operational taxonomic units detected in the original faeces. Over 54% of 0.41% (w/v) DBHB was metabolised by microbiota models originating from seven faecal samples after 30 h of fermentation (regarded as DBHB utilisers); however, <19% of DBHB was metabolised by microbiota models from five faecal samples (regarded as non-utilisers of DBHB). In utilisers, DBHB administration increased the relative abundance of the genus Coprococcus, correlated with increased butyrogenesis. Increased butyrogenesis was not observed in DBHB non-utilisers. Based on PICRUSt analysis, the relative abundance of ß-hydroxybutyrate dehydrogenase was maintained in microbiota models from DBHB utilisers following DBHB administration; however, it decreased in microbiota models from non-utilisers. After 21 h of fermentation, the intracellular glutamate concentration, which is indicative of growth, showed a positive correlation with DBHB utilisation (R2 = 0.70). Human colonic microbiotas with high growth activity demonstrate efficient utilisation of DBHB for increased butyrate production, which affords health benefits.


Assuntos
Ácido 3-Hidroxibutírico/metabolismo , Butiratos/metabolismo , Clostridiales/metabolismo , Colo/metabolismo , Fezes/microbiologia , Microbioma Gastrointestinal , Clostridiales/genética , Clostridiales/isolamento & purificação , Colo/microbiologia , DNA Bacteriano/genética , Humanos , Técnicas In Vitro , Metaboloma
9.
Proc Natl Acad Sci U S A ; 117(21): 11648-11657, 2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-32398370

RESUMO

The intestinal mucosa exists in dynamic balance with trillions of luminal microbes. Disruption of the intestinal epithelial barrier, commonly observed in mucosal inflammation and diseases such as inflammatory bowel diseases (IBDs), is often associated with dysbiosis, particularly decreases in species producing short-chain fatty acids (SCFAs), such as butyrate. It remains unclear to what extent microbiota-derived factors contribute to the overall maintenance of intestinal homeostasis. Initial studies revealed that butyrate selectively promotes epithelial barrier function and wound healing. We aimed to define the specific mechanism(s) through which butyrate contributes to these epithelial responses. Guided by an unbiased profiling approach, we identified the dominant regulation of the actin-binding protein synaptopodin (SYNPO). Extensions of this work revealed a role for SYNPO in intestinal epithelial barrier function and wound healing. SYNPO was localized to the intestinal epithelial tight junction and within F-actin stress fibers where it is critical for barrier integrity and cell motility. Butyrate, but not other SCFAs, induced SYNPO in epithelial cell lines and murine colonic enteroids through mechanisms possibly involving histone deacetylase inhibition. Moreover, depletion of the microbiota abrogated expression of SYNPO in the mouse colon, which was rescued with butyrate repletion. Studies in Synpo-deficient mice demonstrated exacerbated disease susceptibility and increased intestinal permeability in a dextran sulfate sodium colitis model. These findings establish a critical role for the microbiota and their products, specifically butyrate, in the regulated expression of SYNPO for intestinal homeostasis and reveal a direct mechanistic link between microbiota-derived butyrate and barrier restoration.


Assuntos
Butiratos/metabolismo , Microbioma Gastrointestinal/fisiologia , Mucosa Intestinal/metabolismo , Proteínas dos Microfilamentos , Animais , Linhagem Celular , Homeostase/fisiologia , Humanos , Camundongos Knockout , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Junções Íntimas/metabolismo
10.
Proc Natl Acad Sci U S A ; 117(21): 11715-11726, 2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-32398371

RESUMO

Campylobacter jejuni monitors intestinal metabolites produced by the host and microbiota to initiate intestinal colonization of avian and animal hosts for commensalism and infection of humans for diarrheal disease. We previously discovered that C. jejuni has the capacity to spatially discern different intestinal regions by sensing lactate and the short-chain fatty acids acetate and butyrate and then alter transcription of colonization factors appropriately for in vivo growth. In this study, we identified the C. jejuni butyrate-modulated regulon and discovered that the BumSR two-component signal transduction system (TCS) directs a response to butyrate by identifying mutants in a genetic screen defective for butyrate-modulated transcription. The BumSR TCS, which is important for infection of humans and optimal colonization of avian hosts, senses butyrate likely by indirect means to alter transcription of genes encoding important colonization determinants. Unlike many canonical TCSs, the predicted cytoplasmic sensor kinase BumS lacked in vitro autokinase activity, which would normally lead to phosphorylation of the cognate BumR response regulator. Instead, BumS has likely evolved mutations to naturally function as a phosphatase whose activity is influenced by exogenous butyrate to control the level of endogenous phosphorylation of BumR and its ability to alter transcription of target genes. To our knowledge, the BumSR TCS is the only bacterial signal transduction system identified so far that mediates responses to the microbiota-generated intestinal metabolite butyrate, an important factor for host intestinal health and homeostasis. Our findings suggest that butyrate sensing by this system is vital for C. jejuni colonization of multiple hosts.


Assuntos
Proteínas de Bactérias , Butiratos/metabolismo , Campylobacter jejuni , Regulação Bacteriana da Expressão Gênica/genética , Monoéster Fosfórico Hidrolases/metabolismo , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Infecções por Campylobacter/microbiologia , Galinhas , Humanos , Monoéster Fosfórico Hidrolases/genética , Transdução de Sinais/genética
11.
Sci Rep ; 10(1): 7705, 2020 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-32382092

RESUMO

Uncontrolled oxidative stress, reported in Salmonella and HIV infections, colorectal cancer or severe acute malnutrition, has been associated with anaerobic gut microbiome alteration, impaired butyrate production, mucosal immunity dysregulation and disruption of host-bacterial mutualism. However, the role of major antioxidant molecules in the human body, such as glutathione, ascorbic acid and uric acid, has been neglected in this context. Here, we performed an in vitro metabolomics study of the 3 most odorous anaerobic microbes isolated from the human gut in our laboratory (Clostridium sporogenes, Clostridium subterminale and Romboutsia lituseburensis) when grown in anaerobiosis or in aerobiosis with these 3 antioxidant molecules via gas and liquid chromatography-mass spectrometry (GC/MS and LC/MS). There was no growth or volatile organic compound production in aerobic cultures without the 3 antioxidant molecules. In anaerobiosis, the major metabolic products of the bacteria were thiols, alcohols and short-chain fatty acid esters. The production of alkanes, cycloheptatriene and, paradoxically, increased butyrate production, was observed in the cultures grown in aerobiosis with the 3 antioxidant molecules. The qualitative shift suggests specific molecular mechanisms that remain to be elucidated. The increased production of butyrate, but also isobutyrate and isovalerate in vitro suggests that these 3 antioxidant molecules contributed to the maintenance and active resilience of host-bacterial mutualism against mucosal oxygen and uncontrolled oxidative stress in vivo.


Assuntos
Antioxidantes/metabolismo , Microbioma Gastrointestinal/genética , Metabolômica , Estresse Oxidativo/genética , Aerobiose/genética , Anaerobiose/genética , Ácido Ascórbico/metabolismo , Butiratos/metabolismo , Cromatografia Líquida , Clostridiales/metabolismo , Clostridium/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Glutationa/metabolismo , Humanos , Oxigênio/metabolismo , Ácido Úrico/metabolismo
12.
J Pediatr Surg ; 55(6): 1088-1093, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32234318

RESUMO

PURPOSE: Butyrate is a short-chain fatty acid produced in the intestine. It is controversial whether butyrate is protective or destructive for the intestinal epithelium in the development of diseases like necrotizing enterocolitis (NEC), and its mechanism of action remains unclear. We aimed to determine the effect of butyrate on the intestinal epithelium by studying its effects on intestinal epithelial cells (IEC-18) exposed to injury and in vivo by investigating the effects on the intestine in an experimental model of NEC. METHODS: A) In vitro study: Butyrate was given to normal IEC-18 to determine the dose triggering injury. Based on above results, low dose butyrate (1 mM) was given to H2O2-injured cells to determine its effect against inflammation. B) In vivo study: NEC was induced by hypoxia and gavage feeding between postnatal day P5 and P9 (n = 8). Breastfed mice were used as control (n = 7). Butyrate (150 mM) was administered by enema on P6 in NEC (n = 6). Distal ileum was harvested on P9. RESULTS: High dose (16 mM) butyrate upregulated inflammatory marker IL-6, while low dose butyrate protected cells from injury by reducing IL-6 expression. Similarly, compared with NEC alone, NEC mice who received butyrate had reduced intestinal damage, reduced IL-6 and NF-ĸB expression, and increased intestinal tight junction marker Claudin-7. CONCLUSION: Butyrate has opposite effects depending on the dose administered. Butyrate can protect cells from H2O2-induced injury and can in vivo protect the intestine from NEC. This beneficial effect is because of downregulation of inflammation and enhancement of intestinal barrier.


Assuntos
Butiratos/metabolismo , Mucosa Intestinal/metabolismo , Animais , Animais Recém-Nascidos , Biomarcadores/metabolismo , Modelos Animais de Doenças , Enterocolite Necrosante/etiologia , Peróxido de Hidrogênio , Íleo/metabolismo , Inflamação/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Junções Íntimas/metabolismo
13.
PLoS One ; 15(4): e0231865, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32315360

RESUMO

Gut microbiome plays an essential role in asthma development, and probiotic-based manipulation of the gut microbiome has been proposed to prevent asthma. Although the preventive effect of Lactobacillus supplementation against allergies has been reported, the precise Lactobacillus species beneficial for effective prevention of asthma remain unidentified and the underlying mechanisms remain unclear. Therefore, we aimed to investigate the efficacy of oral administration of six Lactobacillus species and the mechanism underlying asthma prevention via gut microbiome modulation. We investigated the effects of oral administration of L. rhamnosus, L. fermentum, L. casei, L. gasseri, L. salivarius, and L. reuteri (five strains of each species) on asthma and gut microbiome of house dust mite (HDM)-treated murine models of asthma. Of these, L. reuteri administration was the most effective: it alleviated airway inflammation, decreased total IgE and HDM-IgG1, and reduced Th2-associated pro-inflammatory cytokines. Moreover, modulation of specific microbial genera by L. reuteri was more effective in asthma prevention than the modulation of the overall microbiota composition. Lactobacillus and Enterococcus were enriched after L. reuteri supplementation and were closely associated with total IgE and IL-13 production. Furthermore, L. reuteri specifically altered the gut microbial function toward butyrate generation. Thus, L. reuteri may reduce the risk of asthma development by modulating specific gut microbiota to improve the lung immune environment. Our study suggests a novel option for gut microbiome manipulation via L. reuteri supplementation for suppression of asthma and other allergic diseases.


Assuntos
Asma/patologia , Microbioma Gastrointestinal , Lactobacillus reuteri/fisiologia , Pyroglyphidae/imunologia , Administração Oral , Animais , Asma/imunologia , Butiratos/metabolismo , Ceco/metabolismo , Modelos Animais de Doenças , Imunoglobulina E/sangue , Interleucina-13/metabolismo , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Camundongos , Células Th2/citologia , Células Th2/imunologia , Células Th2/metabolismo
14.
J Dairy Sci ; 103(7): 6209-6217, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32331886

RESUMO

Current feeding systems are based on the assumption that the AA profile of rumen undegraded protein is similar to that of the original feed. The objective of this experiment was to determine rumen bacterial degradation of individual essential AA in fish meal (FM) and blood meal (BM). Eight dual-flow continuous-culture fermentors were used in a completely randomized block design with a factorial arrangement of treatments and 3 replicated periods. Fermentors were supplied with 95 g of dry matter/d of isonitrogenous diets. Treatments contained a nonprotein N source (urea and tryptone) that was substituted with increasing proportions of FM or BM (0, 33, 67, or 100%). Diets consisted of 22.0% crude protein, 35.2% neutral detergent fiber, 34.6% nonfiber carbohydrates, 2.0% ether extract, and 9.2% ash. We hypothesized that the increase in the flow of individual AA would be attributed to the increase in the supply of the AA from each protein supplement. True organic matter degradation was decreased by increasing levels of FM or BM, but did not affect degradation of neutral detergent fiber and acid detergent fiber, total volatile fatty acids (VFA) concentration, or the molar proportion of propionate. There was a substrate by level of inclusion interaction in acetate molar proportion and branched-chain VFA. Butyrate concentration decreased linearly with increasing levels of FM and BM in treatment. Changes in branched-chain VFA reflected differences in content of branched-chain AA between supplements and the level of inclusion, although the quadratic effect suggests that other factors were involved. Ammonia-N concentration showed a substrate by level of inclusion interaction. Total dietary N and AA flows increased with increasing levels of FM or BM in treatment. The efficiency of bacterial crude protein synthesis was not affected by treatment, but the flow of bacterial N decreased in FM diets as the level of FM increased. Flows of AA increased linearly with increasing levels of the respective AA from supplements. Arginine, Ile, Met and Phe were more degradable, while His was more resistant to bacterial degradation. Results suggest that the resistance to rumen bacterial degradation of individual AA varies within FM and BM protein and may affect the estimates of dietary supply of individual AA to the small intestine.


Assuntos
Aminoácidos Essenciais/metabolismo , Reatores Biológicos , Sangue , Produtos Pesqueiros/análise , Rúmen/metabolismo , Amônia/metabolismo , Animais , Bactérias/metabolismo , Butiratos/metabolismo , Digestão , Ácidos Graxos/metabolismo , Ácidos Graxos Voláteis/metabolismo , Feminino , Fermentação , Ureia/metabolismo
15.
J Dairy Sci ; 103(6): 5047-5060, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32278566

RESUMO

Ruminants are born with an undeveloped physical, metabolic, and microbial rumen. Rumen development is limited under artificial rearing systems when newborn animals are separated from the dam, fed on milk replacer, and weaned at an early age. This study aims to evaluate the effects of early-life inoculation of young ruminants with rumen fluid from adult animals. Eighty newborn goat kids were randomly allocated to 1 of 4 experimental treatments and inoculated daily from d 1 to wk 11 with autoclaved rumen fluid (AUT), fresh rumen fluid obtained from adult goats fed either a forage diet (RFF) or concentrate-rich diet (RFC), or absence of inoculation (CTL). Goat kids were artificially reared with ad libitum access to milk replacer, starter concentrate, and forage hay. Blood was sampled weekly and rumen microbial fermentation was monitored at 5 (preweaning), 7 (weaning), and 9 wk of age (postweaning). Results indicated that inoculation with fresh rumen fluid accelerated the rumen microbial and fermentative development before weaning. As a result, RFC and RFF animals had higher solid feed intake (+73%), rumen concentrations of ammonia-N (+26%), total volatile fatty acids (+46%), butyrate (+50%), and plasma ß-hydroxybutyrate (+48%), and lower milk intake (-6%) than CTL and AUT animals at wk 5. Inoculation with fresh inoculum also promoted early rumen colonization by a complex and abundant protozoal community, whereas CTL animals remained protozoa free. Although all kids experienced moderate growth retardation during 1 wk after weaning, inoculation with fresh rumen fluid favored the weaning process, leading to 2.2 times higher weight gain than CTL and AUT animals during wk 8. Some of these advantages were retained during the postweaning period and RFF and RFC animals showed higher forage intake (up to +44%) than CTL and AUT animals with no detrimental effects on feed digestibility or stress levels. The superior microbial load of RFC compared with RFF inoculum tended to provide further improvements in terms of forage intake, plasma ß-hydroxybutyrate, and rumen protozoa, whereas AUT inoculation provided minor (if any) advantages with respect to CTL animals. Although no differences were noted on animal growth, this study suggests that early life inoculation of goat kids with rumen microbiota can represent an effective strategy to accelerate the rumen development, facilitating a smooth transition from milk to solid feed and to the potential implementation of early weaning strategies.


Assuntos
Líquidos Corporais , Cabras , Rúmen , Desmame , Ácido 3-Hidroxibutírico/sangue , Ração Animal , Animais , Animais Recém-Nascidos , Líquidos Corporais/metabolismo , Butiratos/metabolismo , Dieta/veterinária , Ácidos Graxos Voláteis/metabolismo , Fermentação , Cabras/metabolismo , Microbiota , Leite/metabolismo , Rúmen/metabolismo , Ganho de Peso
16.
Chin J Nat Med ; 18(2): 90-102, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32172952

RESUMO

With the occurrence of aging process, decreased neuron dopamine, disrupted brown adipose tissue (BAT) remodeling and decreased butyrate level all reflect a weak host healthy in certain degree. Nevertheless, the signs of mid-adult gut microbiota, and its association with host healthy are not well understood. In current study, we deemed to illustrate the associations of age, neuron dopamine, BAT remodeling, butyrate and gut microbiota with the aid of traditional herbal formula Kang Shuai Lao Pian (KSLP), which is known for its anti-aging effect. Here, ELISA was performed to detect the production of brain dopamine, the mass of inguinal white adipose tissue versus interscapular brown adipose tissue (iWAT/iBAT) was calculated and considered as a sign of BAT remodeling, 16S rRNA gene sequencing was used to the detection of gut microbiota profiling and gas chromatography was used to measure the butyrate level in mice feces. Our results indicated mid-adult mice already present distinctive gut microbiota profiling compared with young mice, concomitant with which are the lower brain dopamine level and disrupted brown adipose remodeling. KSLP treatment improved the host healthy and regulated gut microbiota with enriched Firmicutes at the expense of Bacteroidetes, particularly increased the relative abundance of bacteria functionally related to dopamine and butyrate productions, which suggest KSLP treatment constructs a healthier gut environment. In conclusion, modulation of gut microbiota and butyrate may connectively regulate dopamine production and BAT remodeling through gut-brain axis and gut-metabolism axis.


Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Butiratos/metabolismo , Dopamina/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Tecido Adiposo Marrom/fisiopatologia , Fatores Etários , Animais , Ceco/microbiologia , Fezes/microbiologia , Feminino , Camundongos
17.
mBio ; 11(1)2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-32019803

RESUMO

Across human populations, 16S rRNA gene-based surveys of gut microbiomes have revealed that the bacterial family Christensenellaceae and the archaeal family Methanobacteriaceae cooccur and are enriched in individuals with a lean, compared to an obese, body mass index (BMI). Whether these association patterns reflect interactions between metabolic partners, as well as whether these associations play a role in the lean host phenotype with which they associate, remains to be ascertained. Here, we validated previously reported cooccurrence patterns of the two families and their association with a lean BMI with a meta-analysis of 1,821 metagenomes derived from 10 independent studies. Furthermore, we report positive associations at the genus and species levels between Christensenella spp. and Methanobrevibacter smithii, the most abundant methanogen of the human gut. By coculturing three Christensenella spp. with M. smithii, we show that Christensenella spp. efficiently support the metabolism of M. smithii via H2 production far better than Bacteroides thetaiotaomicron does. Christensenella minuta forms flocs colonized by M. smithii even when H2 is in excess. In culture with C. minuta, H2 consumption by M. smithii shifts the metabolic output of C. minuta's fermentation toward acetate rather than butyrate. Together, these results indicate that the widespread cooccurrence of these microorganisms is underpinned by both physical and metabolic interactions. Their combined metabolic activity may provide insights into their association with a lean host BMI.IMPORTANCE The human gut microbiome is made of trillions of microbial cells, most of which are Bacteria, with a subset of Archaea The bacterial family Christensenellaceae and the archaeal family Methanobacteriaceae are widespread in human guts. They correlate with each other and with a lean body type. Whether species of these two families interact and how they affect the body type are unanswered questions. Here, we show that species within these families correlate with each other across people. We also demonstrate that particular species of these two families grow together in dense flocs, wherein the bacteria provide hydrogen gas to the archaea, which then make methane. When the archaea are present, the ratio of bacterial products (which are nutrients for humans) is changed. These observations indicate that when these species grow together, their products have the potential to affect the physiology of their human host.


Assuntos
Índice de Massa Corporal , Clostridiales/metabolismo , Microbioma Gastrointestinal , Hidrogênio/metabolismo , Methanobrevibacter/metabolismo , Acetatos/metabolismo , Butiratos/metabolismo , Clostridiales/genética , Fezes/microbiologia , Fermentação , Humanos , Metanálise como Assunto , Metano/metabolismo , Methanobrevibacter/genética , Interações Microbianas , Obesidade/microbiologia , RNA Ribossômico 16S/genética
18.
Cell Host Microbe ; 27(3): 389-404.e6, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32004499

RESUMO

Dietary fibers (DFs) impact the gut microbiome in ways often considered beneficial. However, it is unknown if precise and predictable manipulations of the gut microbiota, and especially its metabolic activity, can be achieved through DFs with discrete chemical structures. Using a dose-response trial with three type-IV resistant starches (RS4s) in healthy humans, we found that crystalline and phosphate cross-linked starch structures induce divergent and highly specific effects on microbiome composition that are linked to directed shifts in the output of either propionate or butyrate. The dominant RS4-induced effects were remarkably consistent within treatment groups, dose-dependent plateauing at 35 g/day, and can be explained by substrate-specific binding and utilization of the RS4s by bacterial taxa with different pathways for starch metabolism. Overall, these findings support the potential of using discrete DF structures to achieve targeted manipulations of the gut microbiome and its metabolic functions relevant to health.


Assuntos
Fibras na Dieta/metabolismo , Ácidos Graxos Voláteis/metabolismo , Microbioma Gastrointestinal , Amido/química , Adulto , Butiratos/metabolismo , Suplementos Nutricionais , Feminino , Humanos , Masculino , Propionatos/metabolismo , Adulto Jovem
19.
EBioMedicine ; 52: 102649, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32062353

RESUMO

Host-microbiota interactions involving inflammatory and metabolic pathways have been linked to the pathogenesis of multiple immune-mediated diseases and metabolic conditions like diabetes and obesity. Accumulating evidence suggests that alterations in the gut microbiome could play a role in cardiovascular disease. This review focuses on recent advances in our understanding of the interplay between diet, gut microbiota and cardiovascular disease, with emphasis on heart failure and coronary artery disease. Whereas much of the literature has focused on the circulating levels of the diet- and microbiota-dependent metabolite trimethylamine-N-oxide (TMAO), several recent sequencing-based studies have demonstrated compositional and functional alterations in the gut microbiomes in both diseases. Some microbiota characteristics are consistent across several study cohorts, such as a decreased abundance of microbes with capacity for producing butyrate. However, the published gut microbiota studies generally lack essential covariates like diet and clinical data, are too small to capture the substantial variation in the gut microbiome, and lack parallel plasma samples, limiting the ability to translate the functional capacity of the gut microbiomes to actual function reflected by circulating microbiota-related metabolites. This review attempts to give directions for future studies in order to demonstrate clinical utility of the gut-heart axis.


Assuntos
Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/metabolismo , Suscetibilidade a Doenças , Microbioma Gastrointestinal , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/metabolismo , Animais , Butiratos/metabolismo , Dieta , Disbiose/metabolismo , Ácidos Graxos Voláteis/biossíntese , Humanos , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Lipopolissacarídeos/metabolismo , Metagenoma , Metagenômica , Transdução de Sinais
20.
Biochem Pharmacol ; 175: 113868, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32088259

RESUMO

Deoxynivalenol (DON) is the most common mycotoxin in grains, and DON exposure causes gastrointestinal inflammation and systemic immunosuppression. The immunosuppression caused by DON has raised serious concerns about whether it is safe to use probiotics in immunocompromised hosts. Gut microbiota remodeling by Lactobacillus is a potential effective strategy to prevent DON exposure. The athymic nude mice were chose as the model of immunocompromised animals. We tested the effect of the probiotic Lactobacillus rhamnosus GG (LGG) or Lactobacillus acidophilus (LA) supplementation on host protection against DON exposure and the underlying mechanisms in nude mice. DON exposure induced endoplasmic reticulum (ER) stress and impaired intestinal barrier function and microbiota, which were relieved by LGG supplementation but not LA supplementation. LGG supplementation significantly enhanced the intestinal barrier function, increased the body weight and the survival rate in nude mice that exposed to DON for two weeks. Furthermore, LGG supplementation modulated the gut microbiota by increasing the abundance of Bacteroidetes and the levels of the butyrate-producing genes But and Buk to promote butyrate production. Butyrate inhibited the IRE1α/XBP1 signaling pathway to reduce DON-induced intestine injury. In conclusion, LGG supplementation modulated the gut microbiota to promote butyrate production, protecting against DON exposure in nude mice. Both LGG and butyrate show promise for use in protecting against DON exposure.


Assuntos
Butiratos/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Enteropatias/prevenção & controle , Lactobacillus rhamnosus/crescimento & desenvolvimento , Probióticos/uso terapêutico , Tricotecenos/toxicidade , Animais , Contaminação de Alimentos , Enteropatias/metabolismo , Enteropatias/microbiologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/microbiologia , Lactobacillus rhamnosus/enzimologia , Masculino , Camundongos , Camundongos Nus , Permeabilidade , Fosfotransferases (Aceptor do Grupo Carboxila)/genética , Fosfotransferases (Aceptor do Grupo Carboxila)/metabolismo , Tricotecenos/metabolismo
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