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1.
J Anim Sci ; 100(8)2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35908781

RESUMO

Optimal athletic performance requires meeting the energetic demands of the muscle fibers, which are a function of myosin ATPase enzymatic activity. Skeletal muscle with a predominant oxidative metabolism underlies equine athletic success. Sodium butyrate, a short-chain fatty acid, can affect muscle fiber composition in pigs. To determine if a similar scenario exists in horses, 12 adult Thoroughbred geldings (7.4 ± 0.6 yr of age; mean ± SEM) were fed 16 g of calcium butyrate (CB) or an equivalent amount of carrier (CON) daily for 30 d in a crossover design. Middle gluteal muscle biopsies were collected before and after the feeding trial for immunohistochemical determination of fiber type, and RNA and protein isolation. After 30 d, CB increased (P < 0.05) the percentage of type IIA fibers and tended (P = 0.13) to reduce the numbers of type IIX fibers in comparison to control (CON). No changes (P > 0.05) in type I, IIA, or IIX fiber size were observed in response to CB. No differences (P > 0.05) were noted in the abundance of succinate dehydrogenase (SDH) protein or activity between horses receiving CB or CON. Myogenin mRNA abundance was unaffected (P > 0.05) by 30 d of CB supplementation. The increase in type IIA fibers in the absence of altered mitochondrial SDH enzymatic activity suggests that CB affects myosin ATPase expression independent of altered metabolism.


The largest tissue in the body, skeletal muscle, is a heterogeneous mix of fibers that are categorized based on their primary source of energy production and speed of contraction. Evidence suggests that Thoroughbred horses with a greater percentage of type IIA, fast-twitch, oxidative fibers are more successful than those with fewer. Pigs fed a diet supplemented with butyrate contained a greater percentage of oxidative muscle fibers. This study examined the ability of calcium butyrate (CB), a short-chain fatty acid, to alter muscle fiber composition in horses. Adult Thoroughbred geldings were supplemented with a placebo or CB for 30 d, and gluteus medius muscle biopsies were retrieved and analyzed for fiber type, myogenin expression, and succinate dehydrogenase (SDH) activity. Results demonstrate a small increase in the percentage of type IIA fibers without a change in SDH activity, a marker of oxidative metabolism. Myogenin expression remained unaffected by CB supplementation. These efforts underscore the need for further research to validate improved exercise performance in response to CB supplementation and identify a mechanism of action for the fatty acid in the equine skeletal muscle.


Assuntos
Cálcio , Cadeias Pesadas de Miosina , Animais , Butiratos/metabolismo , Cálcio/metabolismo , Suplementos Nutricionais , Cavalos , Masculino , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Cadeias Pesadas de Miosina/genética , Cadeias Pesadas de Miosina/metabolismo , Miosinas , Estresse Oxidativo , Suínos
2.
BMC Microbiol ; 22(1): 183, 2022 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-35869433

RESUMO

BACKGROUND: Polyhydroxybutyrate (PHB) is a biopolymer formed by some microbes in response to excess carbon sources or essential nutrient depletion. PHBs are entirely biodegradable into CO2 and H2O under aerobic and anaerobic conditions. It has several applications in various fields such as medicine, pharmacy, agriculture, and food packaging due to its biocompatibility and nontoxicity nature. RESULT: In the present study, PHB-producing bacterium was isolated from the Dirout channel at Assiut Governorate. This isolate was characterized phenotypically and genetically as Bacillus cereus SH-02 (OM992297). According to one-way ANOVA test, the maximum PHB content was observed after 72 h of incubation at 35 °C using glucose and peptone as carbon and nitrogen source. Response surface methodology (RSM) was used to study the interactive effects of glucose concentration, peptone concentration, and pH on PHB production. This result proved that all variables have a significant effect on PHB production either independently or in the interaction with each other. The optimized medium conditions with the constraint to maximize PHB content and concentration were 22.315 g/L glucose, and 15.625 g/L peptone at pH 7.048. The maximum PHB content and concentration were 3100.799 mg/L and 28.799% which was close to the actual value (3051 mg/l and 28.7%). The polymer was identified as PHB using FTIR, NMR, and mass spectrometry. FT-IR analysis showed a strong band at 1724 cm- 1 which attributed to the ester group's carbonyl while NMR analysis has different peaks at 169.15, 67.6, 40.77, and 19.75 ppm that were corresponding to carbonyl, methine, methylene, and methyl resonance. Mass spectroscopy exhibited molecular weight for methyl 3- hydroxybutyric acid. CONCLUSION: PHB-producing strain was identified as Bacillus cereus SH-02 (OM992297). Under optimum conditions from RSM analysis, the maximum PHB content and concentration of this strain can reach (3100.799 mg/L and 28.799%); respectively. FTIR, NMR, and Mass spectrometry were used to confirm the polymer as PHB. Our results demonstrated that optimization using RSM is one of the strategies used for reducing the production cost. RSM can determine the optimal factors to produce the polymer in a better way and in a larger quantity without consuming time.


Assuntos
Bacillus cereus , Butiratos/metabolismo , Peptonas , Bacillus cereus/genética , Carbono , Glucose , Hidroxibutiratos , Poliésteres , Polímeros , Espectroscopia de Infravermelho com Transformada de Fourier
3.
Cell Immunol ; 378: 104575, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35779312

RESUMO

Con A-induced hepatitis is the most commonly used animal model for simulating autoimmune hepatitis (AIH). In this study, we investigated whether methyl butyrate (MB) alleviates Con A-induced hepatitis and how it affects Con A-stimulated lymphocytes. MB improves liver function in AIH mice, reducing the expression of several inflammatory cytokines and Th1 cell-associated chemokines in the liver, while significantly inhibiting toll-like receptor signaling pathway. Also in the liver, we verified that infiltrating Th1 cells were fewer after MB treatment. In vitro, we found that the activation of both human and mouse Th1 cells by Con A were inhibited by MB and the human-derived cells were even more sensitive. And MB caused a reduction in IFN-γ secretion together with TNF-α and IL-6. The above findings suggest that MB inhibits the activation and homing of Th1 cells to the liver, thereby attenuating Con A-induced liver injury, and may be a potential therapeutic agent for AIH.


Assuntos
Hepatite Autoimune , Animais , Butiratos/metabolismo , Butiratos/farmacologia , Concanavalina A , Hepatite Autoimune/etiologia , Humanos , Fígado , Camundongos , Camundongos Endogâmicos C57BL
4.
PLoS One ; 17(7): e0269872, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35834581

RESUMO

Short-chain fatty acids contribute to normal bowel function and prevent bacterial infections. In particular, butyrate is a promising candidate that plays an important role in regulating the functional integrity of the gastrointestinal tract by stimulating mucin secretion. We investigated whether butyrate treatment modulates mucin secretion and bacterial adherence in LoVo cells. In addition, the possible signaling pathways were also examined in connection with the upregulation of mucin secretion. The results showed that butyrate induced mucin secretion in LoVo cells, resulting in the inhibition of Escherichia coli adhesion by increasing the adherence of Lactobacillus acidophilus and Bifidobacterium longum. The gene expression analysis suggests that mitogen-activated protein kinase (MAPK) signaling pathways including Cdc42-PAK pathway appears to be involved in stimulating mucin secretion. More importantly, butyrate induced the increased actin expression and polymerization in LoVo cells, which could be attributable to the Cdc42-PAK signaling pathway, implicated in actin cytoskeleton and mucin secretion. Our results provide a molecular basis in modulating bacterial adherence and the MAPK signaling pathway for the improved homeostasis of colonic epithelial cells.


Assuntos
Butiratos , Mucinas , Butiratos/metabolismo , Butiratos/farmacologia , Mucosa Intestinal/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Mucina-2/metabolismo , Mucinas/metabolismo , Transdução de Sinais
5.
Nutrients ; 14(14)2022 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-35889783

RESUMO

Short-chain fatty acids (SCFA) produced from dietary non-digestible carbohydrate fermentation have metabolic effects in skeletal muscle; however, their effect on inflammatory mediator production is unknown. In this study, L6 myotubes were cultured with individual SCFA (acetate, propionate, and butyrate) at 0.5 mM and 2.5 mM ± 10 ng/mL lipopolysaccharide (LPS) or ± 500 µM palmitic acid (PA) for 24 h. In response to LPS, only butyrate had an effect at the lower concentration (0.5 mM), whereas at the higher concentration (2.5 mM) both propionate and butyrate reduced MCP-1, MIP-1α, and RANTES secretion (p < 0.05), and only butyrate reduced IL-6 secretion and intracellular protein levels of phospho-STAT3 (p < 0.05). In response to PA, 0.5 mM butyrate reduced protein expression of phospho-NFκB p65 and the secretion of IL-6, MIP-1α, and MCP-1, whereas all three SCFA reduced RANTES secretion (p < 0.05). At the 2.5 mM SCFA concentration combined with PA stimulation, all three SCFA reduced intracellular protein expression of phospho-NFκB p65 and phospho-STAT3 and secreted protein levels of MCP-1, IL-6, and RANTES, whereas only butyrate reduced secretion of MIP-1α (p < 0.05). Thus, SCFA exhibit differential effects on inflammatory mediator expression in response to LPS and PA stimulation, which has implications for their individual impacts on inflammation-mediated skeletal muscle dysfunction.


Assuntos
Lipopolissacarídeos , Propionatos , Butiratos/metabolismo , Quimiocina CCL3 , Quimiocina CCL5 , Carboidratos da Dieta , Ácidos Graxos Voláteis/metabolismo , Ácidos Graxos Voláteis/farmacologia , Interleucina-6 , Lipopolissacarídeos/farmacologia , Fibras Musculares Esqueléticas/metabolismo , Ácido Palmítico/farmacologia , Propionatos/metabolismo
6.
Nutrients ; 14(15)2022 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-35893896

RESUMO

The pathogenesis of ulcerative colitis (UC) is unclear, but it is generally believed to be closely related to an imbalance in gut microbiota. Roseburia intestinalis (R. intestinalis) might play a key role in suppressing intestinal inflammation, but the mechanism of its anti-inflammatory effect is unknown. In this study, we investigated the role of R. intestinalis and Toll-like receptor 5 (TLR5) in relieving mouse colitis. We found that R. intestinalis significantly upregulated the transcription of TLR5 in intestinal epithelial cells (IECs) and improved colonic inflammation in a colitis mouse model. The flagellin of R. intestinalis activated the release of anti-inflammatory factors (IL-10, TGF-ß) and reduced inflammation in IECs. Furthermore, butyrate, the main metabolic product secreted by R. intestinalis, regulated the expression of TLR5 in IECs. Our data show that butyrate increased the binding of the transcription factor Sp3 (specificity protein 3) to the TLR5 promoter regions, upregulating TLR5 transcription. This work provides new insight into the anti-inflammatory effects of R. intestinalis in colitis and a potential target for UC prevention and treatment.


Assuntos
Colite Ulcerativa , Colite , Animais , Anti-Inflamatórios/farmacologia , Butiratos/metabolismo , Butiratos/farmacologia , Clostridiales , Colite/metabolismo , Colite Ulcerativa/metabolismo , Inflamação/metabolismo , Mucosa Intestinal/metabolismo , Camundongos , Transdução de Sinais , Receptor 5 Toll-Like/genética , Receptor 5 Toll-Like/metabolismo
7.
Molecules ; 27(15)2022 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-35897919

RESUMO

Inflammatory bowel disease is characterized by a radical imbalance of inflammatory signaling pathways in the gastrointestinal tract, and it is categorized into two diseases, such as Crohn's disease and ulcerative colitis. In this study, we investigated anti-inflammatory activities using fermented Curcuma that contains butyrate (FB). Nitric oxide production in RAW 264.7 cells and the expression of inducible nitric oxide synthase in the intestinal mucosa appears to be enhanced in active ulcerative colitis. Here, the cytotoxicity, physiological activity, and anti-inflammatory efficacy of FB in colitis animals were investigated. To verify the anti-inflammatory effect, this study was conducted using the dextran sulfate sodium (DSS)-induced colitis mice model. As a result, non-toxicity was confirmed, and anti-inflammatory effects were revealed by inducing a reduction of LPS-induced NO production. In the DSS-induced colitis, reduced weight was recovered and a decrease in inflammatory factors Ig-E and TNF-α in the mesenteric lymph node (MLN) and spleen was induced, and it was confirmed to help with the morphological remodeling of the intestine. In conclusion, this paper suggests that FB can help to alleviate intestinal inflammation and to improve the intestinal environment, with the help of morphological remodeling.


Assuntos
Colite Ulcerativa , Colite , Animais , Anti-Inflamatórios/uso terapêutico , Butiratos/metabolismo , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Colo/metabolismo , Curcuma/metabolismo , Citocinas/metabolismo , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL
8.
Appl Environ Microbiol ; 88(13): e0039122, 2022 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-35699440

RESUMO

Syntrophic anaerobic consortia comprised of fatty acid-degrading bacteria and hydrogen/formate-scavenging methanogenic archaea are of central importance for balanced and resilient natural and manufactured ecosystems: anoxic sediments, soils, and wastewater treatment bioreactors. Previously published studies investigated interaction between the syntrophic bi-cultures, but little information is available on the influence of fermentative bacteria on syntrophic fatty acid oxidation, even though fermentative organisms are always present together with syntrophic partners in the above-mentioned ecosystems. Here, we present experimental observations of stimulated butyrate oxidation and methane generation by a coculture of Syntrophomonas wolfei with any of the following methanogens: Methanospirillum hungatei, Methanobrevibacter arboriphilus, or Methanobacterium formicicum due to the addition of a fermentative Trichococcus flocculiformis strain ES5. The addition of T. flocculiformis ES5 to the syntrophic cocultures led to an increase in the rates of butyrate consumption (120%) and volumetric methane production (150%). Scanning electron microscopy of the most positively affected coculture (S. wolfei, M. hungatei, and T. flocculiformis ES5) revealed a tendency of T. flocculiformis ES5 to aggregate with the syntrophic partners. Analysis of coculture's proteome with or without addition of the fermentative bacterium points to a potential link with signal transducing systems of M. hungatei, as well as activation of additional butyryl coenzyme A dehydrogenase and an electron transfer flavoprotein in S. wolfei. IMPORTANCE Results from the present study open doors to fascinating research on complex microbial cultures in anaerobic environments (of biotechnological and ecological relevance). Such studies of defined mixed populations are critical to understanding the highly intertwined natural and engineered microbial systems and to developing more reliable and trustable metabolic models. By investigating the existing cultured microbial consortia, like the ones described here, we can acquire knowledge on microbial interactions that go beyond "who feeds whom" relations but yet benefit the parties involved. Transfer of signaling compounds and stimulation of gene expression are examples of indirect influence that members of mixed communities can exert on each other. Understanding such microbial relationships will enable development of new sustainable biotechnologies with mixed microbial cocultures and contribute to the general understanding of the complex natural microbial interactions.


Assuntos
Euryarchaeota , Methanospirillum , Bactérias/genética , Butiratos/metabolismo , Carnobacteriaceae , Clostridiales , Técnicas de Cocultura , Ecossistema , Euryarchaeota/metabolismo , Metano/metabolismo , Methanospirillum/metabolismo
9.
Food Chem ; 393: 133392, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-35679706

RESUMO

Flesh quality is influenced by diet components, but the underlying mechanism remains unclear. This study aimed to investigate the effect of replacing soybean meal (SBM) protein with cottonseed protein concentrate (CPC) at different levels (0%, CK; 15%, CPC15; 30%, CPC30 and 45%, CPC45) on the flesh quality of Nile tilapia. The results indicated that different protein sources influenced muscle amino acid composition instead of fatty acid composition. Lower muscle lipid content was found in CPC45, which in turn significantly altered the muscle texture. The hepatic lipid metabolism-related genes were detected and we found that CPC45 significantly suppressed the lipogenesis and promoted lipolysis. Higher content of microbiota-derived butyrate was found in the intestinal content of CPC45 and butyrate could decrease the lipid accumulation in vitro. Replacing SBM with CPC increased the intestinal butyrate to suppress the lipogenesis in the liver which may account for the increased muscle hardness.


Assuntos
Ciclídeos , Microbiota , Ração Animal/análise , Animais , Butiratos/metabolismo , Ciclídeos/genética , Ciclídeos/metabolismo , Músculos
10.
Food Funct ; 13(13): 7046-7061, 2022 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-35678197

RESUMO

Inflammatory bowel disease (IBD) is an idiopathic inflammatory bowel disease. Modulation of gut microbiota with dietary and nutritional targets is a feasible strategy for the prevention and treatment of IBD. In this study, we focused on Clostridium butyricum Prazmowski (CB), a butyrate-producing potential probiotic. We found that CB feeding decreased the disease activity index, colon inflammation/injury score and cell apoptosis in an experimental colitis mouse model, as well as elevated the level of SCFAs in cecal feces. CB could also balance the inflammatory cytokines, protect tight junctions, and increase the number of goblet cells and MUC2 production in mice, accompanied by EGFR signaling activation triggered by heparin-binding epidermal growth factor (HB-EGF) and amphiregulin (AREG). From the perspective of mechanism, the CB supernatant (CBS) stimulated EGFR activation in colon epithelial cell lines in concentration-dependent and time-dependent manners. CBS reduced the damage of tight junctions induced by H2O2, and inhibition of EGFR could suppress the protective effect of CBS. In conclusion, CB could protect the gut barrier and alleviate experimental colitis through the transactivation of EGFR signaling in intestinal epithelial cells induced by ligands (HB-EGF and AREG). This study identified the potential efficacy of CB as a preventive strategy for IBD and showed the broad prospect of CB as a food supplement.


Assuntos
Clostridium butyricum , Colite , Doenças Inflamatórias Intestinais , Probióticos , Animais , Butiratos/metabolismo , Clostridium butyricum/fisiologia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/prevenção & controle , Fator de Crescimento Epidérmico/metabolismo , Receptores ErbB/metabolismo , Fator de Crescimento Semelhante a EGF de Ligação à Heparina/metabolismo , Peróxido de Hidrogênio/metabolismo , Camundongos , Probióticos/metabolismo
11.
Biochem Biophys Res Commun ; 613: 81-86, 2022 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-35537289

RESUMO

Butyrate producing bacteria are one of the major components of the human gut microbiota. Their major metabolite, butyrate, has several beneficial properties for host health. Fructooligosaccharides (FOSs) are well documented prebiotics and are hydrolyzed by intracellular glycoside hydrolase family 32 (GH32) enzyme in several butyrate producers, whereas butyrate producers Anaerostipes hadrus and Anaerostipes butyraticus possess extracellular GH32 enzymes. The present study characterized the extracellular GH32 enzymes in the organisms to consider possible cross-feeding of FOSs with other microbes. Culture supernatant of A. hadrus actively hydrolyzed kestose and nystose, i.e., degrees of polymerization 3 and 4 FOSs, respectively, whereas that of A. butyraticus did not hydrolyzed. When co-cultured with Lacticaseibacillus rhamnosus GG in the presence of nystose, which was negative for growth on the FOSs but positive for growth on FOS degradants, A. hadrus promoted the growth of L. rhamnosus GG, but A. butyraticus did not. The observed negative results in A. butyraticus would be due to the presence of a stop codon in the gene encoding extracellular GH32. Genomic analysis revealed that A. hadrus conserved a single extracellular GH32 enzyme at the species level. The enzyme was phylogenetically distinguished into two groups, but the two groups shared similar FOS degradation properties. The results obtained here suggested that A. hadrus is active for extracellular degradation of FOSs and provides its degradants to other microbes. This study provides a basis of knowledge to understand how ingested FOSs are co-metabolized in gut microbiota.


Assuntos
Microbioma Gastrointestinal , Oligossacarídeos , Butiratos/metabolismo , Clostridiales , Glicosídeo Hidrolases/genética , Glicosídeo Hidrolases/metabolismo , Humanos , Oligossacarídeos/metabolismo , Prebióticos
12.
Biomed Pharmacother ; 151: 113163, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35617803

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer. The characteristic excessive stromatogenesis accompanying the growth of this tumor is believed to contribute to chemoresistance which, together with drug toxicity, results in poor clinical outcome. An increasing number of studies are showing that gut microbiota and their metabolites are implicated in cancer pathogenesis, progression and response to therapies. In this study we tested butyrate, a product of dietary fibers' bacterial fermentation, whose anticancer and anti-inflammatory functions are known. We provided in vitro evidence that, beside slowing proliferation, butyrate enhanced gemcitabine effectiveness against two human pancreatic cancer cell lines, mainly inducing apoptosis. In addition, we observed that, when administered to a PDAC mouse model, alone or combined with gemcitabine treatment, butyrate markedly reduced the cancer-associated stromatogenesis, preserved intestinal mucosa integrity and affected fecal microbiota composition by increasing short chain fatty acids producing bacteria and decreasing some pro-inflammatory microorganisms. Furthermore, a biochemical serum analysis showed butyrate to ameliorate some markers of kidney and liver damage, whereas a metabolomics approach revealed a deep modification of lipid metabolism, which may affect tumor progression or response to therapy. Such results support that butyrate supplementation, in addition to conventional therapies, can interfere with pancreatic cancer biology and response to treatment and can alleviate some damages associated to cancer itself or to chemotherapy.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Animais , Bactérias/metabolismo , Butiratos/metabolismo , Butiratos/farmacologia , Butiratos/uso terapêutico , Carcinoma Ductal Pancreático/tratamento farmacológico , Linhagem Celular Tumoral , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Camundongos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia
13.
Int J Mol Sci ; 23(10)2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35628549

RESUMO

Regulatory T cells (Tregs) control immune system activity and inhibit inflammation. While, in mice, short-chain fatty acids (SCFAs) are known to be essential regulators of naturally occurring and in vitro induced Tregs (iTregs), data on their contribution to the development of human iTregs are sparse, with no reports of the successful SCFAs-augmented in vitro generation of fully functional human iTregs. Likewise, markers undoubtedly defining human iTregs are missing. Here, we aimed to generate fully functional human iTregs in vitro using protocols involving SCFAs and to characterize the underlying mechanism. Our target was to identify the potential phenotypic markers best characterizing human iTregs. Naïve non-Treg CD4+ cells were isolated from the peripheral blood of 13 healthy adults and cord blood of 12 healthy term newborns. Cells were subjected to differentiation toward iTregs using a transforming growth factor ß (TGF-ß)-based protocol, with or without SCFAs (acetate, butyrate, or propionate). Thereafter, they were subjected to flow cytometric phenotyping or a suppression assay. During differentiation, cells were collected for chromatin-immunoprecipitation (ChIP)-based analysis of histone acetylation. The enrichment of the TGF-ß-based protocol with butyrate or propionate potentiated the in vitro differentiation of human naïve CD4+ non-Tregs towards iTregs and augmented the suppressive capacity of the latter. These seemed to be at least partly underlain by the effects of SCFAs on the histone acetylation levels in differentiating cells. GITR, ICOS, CD39, PD-1, and PD-L1 were proven to be potential markers of human iTregs. Our results might boost the further development of Treg-based therapies against autoimmune, allergic and other chronic inflammatory disorders.


Assuntos
Ácidos Graxos Voláteis , Propionatos , Linfócitos T Reguladores , Butiratos/metabolismo , Butiratos/farmacologia , Diferenciação Celular , Ácidos Graxos Voláteis/metabolismo , Ácidos Graxos Voláteis/farmacologia , Histonas/metabolismo , Humanos , Recém-Nascido , Propionatos/metabolismo , Propionatos/farmacologia , Linfócitos T Reguladores/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo
14.
J Dairy Sci ; 105(7): 5747-5760, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35599024

RESUMO

This study evaluated the effects of duration of high-concentrate feeding on ruminal and fecal fermentation profile, as well as selected systemic health biomarkers in nonlactating cows supplemented with or without a phytogenic feed additive (PHY). In addition, ruminal degradation kinetics and total-tract nutrient digestibility were evaluated when feeding either only forage or a high-concentrate diet. Nine nonlactating, cannulated Holstein cows were used in a crossover design. Each period included 1 wk of forage feeding (wk 0), diet transition, and 4 wk on the high-concentrate diet (1, 2, 3 and wk 4; 65% dry matter basis). Cows received PHY or not (control). Compared with wk 0, from wk 1 onward, cows on high concentrate showed greater reticular, ruminal, and fecal total volatile fatty acids (VFA), with a greater level of VFA in the rumen than in the hindgut. However, ruminal fermentation was modulated differently by PHY, which showed increased total VFA in wk 1 and increased butyrate in wk 2 in the particle-associated fluid of rumen. In the hindgut, PHY increased propionate in wk 3. Cows fed a high-concentrate diet from wk 1 and onward also showed greater ruminal lactate, as well as lower ruminal and fecal pH, independent of PHY. In addition, compared with cows in wk 1 on a high-concentrate diet, cows in wk 4 had a greater total VFA in free fluid of the rumen and lower fecal pH. Compared with cows at wk 0, cows at wk 1 on high concentrate onward showed greater serum amyloid A and greater activity of glutamate dehydrogenase. In contrast, the high-concentrate diet decreased in situ ruminal degradability of grass silage but increased degradability of corn grain as well as total-tract nutrient digestibility, with total-tract neutral detergent fiber digestibility being greater for cows on the PHY treatment. Overall, from the start of high-concentrate feeding, gut fermentation increased, but differently according to location or PHY, with a stronger build-up of VFA in the rumen compared with the hindgut. In addition, a longer duration on high concentrate exacerbated gut acidification. The enhancing effects of PHY on total VFA and butyrate in particle-associated fluid of the rumen suggest beneficial effects of PHY on particle-associated bacteria, likely contributing to the increased neutral detergent fiber digestibility. The greater production of ruminal butyrate with PHY may be beneficial for the host, given the health benefits of this acid, but more research is needed to elucidate the effects on gut microbiota and the effects of increased butyrate in nonlactating dairy cows.


Assuntos
Ração Animal , Rúmen , Ração Animal/análise , Animais , Butiratos/metabolismo , Bovinos , Detergentes/metabolismo , Dieta/veterinária , Fibras na Dieta/metabolismo , Digestão , Ácidos Graxos Voláteis/metabolismo , Feminino , Fermentação , Lactação , Leite/metabolismo , Nutrientes , Rúmen/metabolismo
15.
EBioMedicine ; 80: 104051, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35561452

RESUMO

BACKGROUND: Current data suggest that dietary fibre (DF) interaction with the gut microbiota largely contributes to their physiological effects. The bacterial fermentation of DF leads to the production of metabolites, most of them are volatile. This study analyzed the breath volatile metabolites (BVM) profile in healthy individuals (n=15) prior and after a 3-week intervention with chitin-glucan (CG, 4.5 g/day), an insoluble fermentable DF. METHODS: The present exploratory study presents the original data related to the secondary outcomes, notably the analysis of BVM. BVM were analyzed throughout the test days -in fasting state and after standardized meals - using selected ion flow tube mass spectrometry (SIFT-MS). BVM production was correlated to the gut microbiota composition (Illumina sequencing, primary outcome), analyzed before and after the intervention. FINDINGS: The data reveal that the post-prandial state versus fasting state is a key determinant of BVM fingerprint. Correlation analyses with fecal microbiota spotlighted butyrate-producing bacteria, notably Faecalibacterium, as dominant bacteria involved in butyrate and other BVM expiration. CG intervention promotes interindividual variations of fasting BVM, and decreases or delays the expiration of most exhaled BVM in favor of H2 expiration, without any consequence on gastrointestinal tolerance. INTERPRETATION: Assessing BVM is a non-invasive methodology allowing to analyze the influence of DF intervention on the gut microbiota. FUNDING: FiberTAG project was initiated from a European Joint Programming Initiative "A Healthy Diet for a Healthy Life" (JPI HDHL) and was supported by the Service Public de Wallonie (SPW-EER, convention 1610365, Belgium).


Assuntos
Microbioma Gastrointestinal , Bactérias/metabolismo , Butiratos/metabolismo , Fibras na Dieta/metabolismo , Ácidos Graxos Voláteis/metabolismo , Fezes/microbiologia , Voluntários Saudáveis , Humanos , Metaboloma
16.
J Nutr Biochem ; 107: 109042, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35533897

RESUMO

Modulation of gut microbiome composition seems to be a promising therapeutic strategy for a wide range of pathologic states. However, these microbiota-targeted interventions may affect production of microbial metabolites, circulating factors in the gut-liver axis influencing hepatic drug metabolism with possible clinical relevance. Butyrate, a short-chain fatty acid produced through microbial fermentation of dietary fibers in the colon, has well established anti-inflammatory role in the intestine, while the effect of butyrate on the liver is unknown. In this study, we have evaluated the effect of butyrate on hepatic AhR activity and AhR-regulated gene expression. We have showed that AhR and its target genes were upregulated by butyrate in dose-dependent manner in HepG2-C3 as well as in primary human hepatocytes. The involvement of AhR has been proved using specific AhR antagonists and siRNA-mediated AhR silencing. Experiments with AhR reporter cells have shown that butyrate regulates the expression of AhR target genes by modulating the AhR activity. Our results suggest also epigenetic action by butyrate on AhR and its repressor (AHRR) presumably through mechanisms based on HDAC inhibition in the liver. Our results demonstrate that butyrate may influence the drug-metabolizing ability of liver enzymes e.g., through the interaction with AhR-dependent pathways.


Assuntos
Butiratos , Microbioma Gastrointestinal , Butiratos/metabolismo , Butiratos/farmacologia , Colo/metabolismo , Ácidos Graxos Voláteis/metabolismo , Humanos , Fígado/metabolismo , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo
17.
Sci Rep ; 12(1): 8771, 2022 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-35610475

RESUMO

Colorectal cancer (CRC) cells shift metabolism toward aerobic glycolysis and away from using oxidative substrates such as butyrate. Pyruvate kinase M1/2 (PKM) is an enzyme that catalyzes the last step in glycolysis, which converts phosphoenolpyruvate to pyruvate. M1 and M2 are alternatively spliced isoforms of the Pkm gene. The PKM1 isoform promotes oxidative metabolism, whereas PKM2 enhances aerobic glycolysis. We hypothesize that the PKM isoforms are involved in the shift away from butyrate oxidation towards glycolysis in CRC cells. Here, we find that PKM2 is increased and PKM1 is decreased in human colorectal carcinomas as compared to non-cancerous tissue. To test whether PKM1/2 alter colonocyte metabolism, we created a knockdown of PKM2 and PKM1 in CRC cells to analyze how butyrate oxidation and glycolysis would be impacted. We report that butyrate oxidation in CRC cells is regulated by PKM1 levels, not PKM2. Decreased butyrate oxidation observed through knockdown of PKM1 and PKM2 is rescued through re-addition of PKM1. Diminished PKM1 lowered mitochondrial basal respiration and decreased mitochondrial spare capacity. We demonstrate that PKM1 suppresses glycolysis and inhibits hypoxia-inducible factor-1 alpha. These data suggest that reduced PKM1 is, in part, responsible for increased glycolysis and diminished butyrate oxidation in CRC cells.


Assuntos
Butiratos , Neoplasias Colorretais , Piruvato Quinase , Butiratos/metabolismo , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/metabolismo , Glicólise , Humanos , Isoenzimas , Piruvato Quinase/metabolismo
18.
Int J Mol Sci ; 23(7)2022 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-35409339

RESUMO

Non-communicable diseases are increasing and have an underlying low-grade inflammation in common, which may affect gut health. To maintain intestinal homeostasis, unwanted epithelial activation needs to be avoided. This study compared the efficacy of butyrate, propionate and acetate to suppress IFN-γ+/-TNF-α induced intestinal epithelial activation in association with their HDAC inhibitory capacity, while studying the canonical and non-canonical STAT1 pathway. HT-29 were activated with IFN-γ+/-TNF-α and treated with short chain fatty acids (SCFAs) or histone deacetylase (HDAC) inhibitors. CXCL10 release and protein and mRNA expression of proteins involved in the STAT1 pathway were determined. All SCFAs dose-dependently inhibited CXCL10 release of the cells after activation with IFN-γ or IFN-γ+TNF-α. Butyrate was the most effective, completely preventing CXCL10 induction. Butyrate did not affect phosphorylated STAT1, nor phosphorylated NFκB p65, but inhibited IRF9 and phosphorylated JAK2 protein expression in activated cells. Additionally, butyrate inhibited CXCL10, SOCS1, JAK2 and IRF9 mRNA in activated cells. The effect of butyrate was mimicked by class I HDAC inhibitors and a general HDAC inhibitor Trichostatin A. Butyrate is the most potent inhibitor of CXCL10 release compared to other SCFAs and acts via HDAC inhibition. This causes downregulation of CXCL10, JAK2 and IRF9 genes, resulting in a decreased IRF9 protein expression which inhibits the non-canonical pathway and CXCL10 transcription.


Assuntos
Butiratos , Histona Desacetilases , Butiratos/metabolismo , Butiratos/farmacologia , Quimiocina CXCL10/genética , Quimiocina CXCL10/metabolismo , Células Epiteliais/metabolismo , Ácidos Graxos Voláteis/farmacologia , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/metabolismo , Humanos , Fator Gênico 3 Estimulado por Interferon, Subunidade gama/metabolismo , RNA Mensageiro/genética , Fator de Necrose Tumoral alfa/metabolismo
19.
Microbiol Spectr ; 10(2): e0254521, 2022 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-35416718

RESUMO

Feeding a growing global population and lowering environmental pollution are the two biggest challenges facing ruminant livestock. Considering the significance of nitrogen metabolism in these challenges, a dietary intervention regarding metabolizable protein profiles with different rumen-undegradable protein (RUP) ratios (high RUP [HRUP] versus low RUP [LRUP]) was conducted in young ruminants with weaned goats as a model. Fecal samples were collected longitudinally for nine consecutive weeks to dissect the timing and duration of intervention, as well as its mechanism of action involving the gut microbiota. Results showed that at least 6 weeks of intervention were needed to distinguish the beneficial effects of HRUP, and HRUP intervention improved the metabolic efficiency of goats as evidenced by enhanced growth performance and nutrient-apparent digestibility at week 6 and week 8 after weaning. Integrated analysis of bacterial diversity, metabolites, and inferred function indicated that HRUP intervention promoted Eubacterium abundance, several pathways related to bacterial chemotaxis pathway, ABC transporters, and butanoate metabolism and thereafter elicited a shift from acetate production toward butyrate and branched-chain amino acid (BCAA) production. Meanwhile, three distinct phases of microbial progression were noted irrespective of dietary treatments, including the enrichment of fiber-degrading Ruminococcus, the enhancement of microbial cell motility, and the shift of fermentation type as weaned goats aged. The current report provides novel insights into early-life diet-microbiota axis triggered by metabolic protein intervention and puts high emphasis on the time window and duration of dietary intervention in modulating lifelong performance of ruminants. IMPORTANCE Precise dietary intervention in early-life gastrointestinal microbiota has significant implications in the long-life productivity and health of young ruminants, as well as in lowering their environmental footprint. Here, using weaned goats as a model, we report that animals adapted to high rumen-undegradable protein diet in a dynamic manner by enriching fecal community that could effectively move toward and scavenge nutrients such as glucose and amino acids and, thereafter, elicit butyrate and BCAA production. Meanwhile, the three dynamic assembly trajectories in fecal microbiota highlight the importance of taking microbiota dynamics into account. Our findings systematically reported when, which, and how the fecal microbiome responded to metabolizable protein profile intervention in young ruminants and laid a foundation for improving the productivity and health of livestock due to the host-microbiota interplay.


Assuntos
Microbioma Gastrointestinal , Cabras , Ração Animal/análise , Animais , Butiratos/metabolismo , Cabras/metabolismo , Cabras/microbiologia , Desmame
20.
Mol Nutr Food Res ; 66(12): e2100884, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35426245

RESUMO

SCOPE: Clostridium butyricum (CB) exerts beneficial actions in several disorders. However, the impact and molecular cues of CB in fat metabolism remain elusive. This study demonstrates the CB inhibition of fat deposition by increasing the relative number of adipose tissue-resident Treg cells (aTregs). METHODS AND RESULTS: CB is administered orally to wild type (WT) mice fed with chow diet, which decrease fat deposition and adipogenic gene expression, associating with elevated serum levels of butyrate. Sodium butyrate (SB) feeding mimics the CB suppression of fat accumulation. Of note, the frequency of aTregs in both the CB and SB treatments, analyzed by flow cytometry, is markedly increased, accompanied by activated Wnt10b expression in white adipose tissues. However, CB and SB fail to inhibit fat deposition in Wnt10b-KO mice. Intriguingly, CB and SB are able to alleviate the obesity, fatty liver, and glucose abnormalities in high fat diet (HFD)-fed WT mice. CONCLUSIONS: These findings suggest that CB, through its metabolite butyrate, inhibits fat deposition via potentiating aTreg cell generation, and support the option of CB and SB for therapeutic interventions in obesity and related disorders.


Assuntos
Clostridium butyricum , Tecido Adiposo/metabolismo , Animais , Butiratos/metabolismo , Dieta Hiperlipídica/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Linfócitos T Reguladores/metabolismo
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