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This study aimed to evaluate the effects of fermented beetroot ketchup enriched with Lactobacillus johnsonii K4 and non-fermented beetroot ketchup on pooled fecal microbiota from healthy adults in in vitro colon model. The research focused on how these products influenced the composition and functionality of the gut microbiota, as well as metabolite production, using the validated dynamic in vitro colon model, TNO Intestinal Model (TIM-2). After an initial starvation phase, a single 60 g dose of predigested and freeze-dried ketchup was introduced into the model. The potential probiotic strain Lactobacillus johnsonii K4 was added over three days. A carbohydrate mixture of standard ileal effluent medium (SIEM) served as the control. Our analysis identified 21 bacterial taxa that were significantly modulated (q-value < 0.2) when comparing ketchup samples to control samples. Notably, the ketchup samples led to an increase in butyrate-producing taxa, including Faecalibacterium, Blautia, Ruminococcaceae, Ruminiclostridium 6, and Anaerostipes. Conversely, there was a reduction in potentially pathogenic genera Desulfovibrio and Escherichia-Shigella. Distinct profiles of short-chain fatty acids (SCFA) were observed among the fermented ketchup, non-fermented ketchup, and control samples. Non-fermented ketchup resulted in higher proportions of acetate, propionate, and butyrate compared to the other interventions. This may be related to the fermentation with lactic acid bacteria in fermented samples with lower levels of substrate for SCFAs production. However, fermented ketchup sample has higher relative abundance of beneficial bacteria like Lactobacillus, Weissella and Dorea in gut microbiota. These findings suggest that beetroot ketchup, can positively influence gut microbiota composition and function, highlighting its potential benefits for human health.
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Colon , Ácidos Grasos Volátiles , Heces , Fermentación , Microbioma Gastrointestinal , Microbioma Gastrointestinal/fisiología , Colon/microbiología , Colon/metabolismo , Humanos , Heces/microbiología , Ácidos Grasos Volátiles/metabolismo , Probióticos , Beta vulgaris/microbiología , Beta vulgaris/química , Adulto , Lactobacillus/metabolismo , Alimentos Fermentados/microbiología , Bacterias/metabolismo , Bacterias/clasificación , Butiratos/metabolismo , MasculinoRESUMEN
Maternal high-fat diet intake has profound effects on the long-term health of offspring, predisposing them to a higher susceptibility to obesity and metabolic dysfunction-associated steatotic liver disease. However, the detailed mechanisms underlying the role of a maternal high-fat diet in hepatic lipid accumulation in offspring, especially at the weaning age, remain largely unclear. In this study, female C57BL/6J mice were randomly assigned to either a high-fat diet or a control diet, and lipid metabolism parameters were assessed in male offspring at weaning. Gut microbiota analysis and targeted metabolomics of short-chain fatty acids (SCFAs) in these offspring were further performed. Both in vivo and in vitro studies were conducted to explore the role of butyrate in hepatic cholesterol excretion in the liver and HepG2 cells. Our results showed that maternal high-fat feeding led to obesity and dyslipidemia, and exacerbated hepatic lipid accumulation in the livers of offspring at weaning. We observed significant decreases in the abundance of the Firmicutes phylum and the Allobaculum genus, known as producers of SCFAs, particularly butyrate, in the offspring of dams fed a high-fat diet. Additionally, maternal high-fat diet feeding markedly decreased serum butyrate levels and down-regulated ATP-binding cassette transporters G5 (ABCG5) in the liver, accompanied by decreased phosphorylated AMP-activated protein kinase (AMPK) and histone deacetylase 5 (HADC5) expressions. Subsequent in vitro studies revealed that butyrate could induce ABCG5 activation and alleviate lipid accumulation via the AMPK-pHDAC5 pathway in HepG2 cells. Moreover, knockdown of HDAC5 up-regulated ABCG5 expression and promoted cholesterol excretion in HepG2 cells. In conclusion, our study provides novel insights into how maternal high-fat diet feeding inhibits hepatic cholesterol excretion and down-regulates ABCG5 through the butyrate-AMPK-pHDAC5 pathway in offspring at weaning.
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Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 5 , Butiratos , Colesterol , Dieta Alta en Grasa , Microbioma Gastrointestinal , Hígado , Ratones Endogámicos C57BL , Animales , Dieta Alta en Grasa/efectos adversos , Femenino , Butiratos/metabolismo , Humanos , Hígado/metabolismo , Células Hep G2 , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 5/metabolismo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 5/genética , Masculino , Colesterol/metabolismo , Colesterol/sangre , Embarazo , Ratones , Metabolismo de los Lípidos , Efectos Tardíos de la Exposición Prenatal/metabolismo , Fenómenos Fisiologicos Nutricionales Maternos , Obesidad/metabolismo , Obesidad/microbiología , Dislipidemias/metabolismo , Dislipidemias/microbiología , Dislipidemias/etiología , LipoproteínasRESUMEN
The gut microbiota significantly contributes to human health and well-being. The aim of this study was to evaluate the stability and resilience of a consortium composed of three next-generation probiotics (NGPs) candidates originally found in the human gut. The growth patterns of Akkermansia muciniphila, Bacteroides thetaiotaomicron, and Faecalibacterium prausnitzii were studied both individually and consortium. The growth kinetics of Akkermansia muciniphila (A. muciniphila), Bacteroides thetaiotaomicron (B. thetaiotaomicron), and Faecalibacterium prausnitzii (F. prausnitzii) were characterized both individually and in consortium using isothermal microcalorimetry and 16S ribosomal RNA next-generation sequencing. The consortium reached stability after three passages and demonstrated resilience to changes in its initial composition. The concentration of butyrate produced was nearly twice as high in the consortium compared to the monoculture of F. prausnitzii. The experimental conditions and methodologies used in this article are a solid foundation for developing further complex consortia.
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Calorimetría , Microbioma Gastrointestinal , ARN Ribosómico 16S , Humanos , Microbioma Gastrointestinal/fisiología , ARN Ribosómico 16S/genética , Faecalibacterium prausnitzii/genética , Akkermansia/crecimiento & desarrollo , Akkermansia/fisiología , Consorcios Microbianos/fisiología , Consorcios Microbianos/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Butiratos/metabolismo , Probióticos , Verrucomicrobia/genética , Verrucomicrobia/crecimiento & desarrollo , Bacteroides/genética , Bacteroides/crecimiento & desarrollo , ADN Bacteriano/genéticaRESUMEN
Sulphated glycosaminoglycans (GAGs) such as heparin are a major component of mast cell granules and form the matrix within which biogenic mediators are stored. Since GAGs released from mast cells also play an important role in helminth expulsion, understanding GAG storage can offer new insights into mast cell function. Sodium butyrate (NaBu), a short-chain fatty acid, causes ultrastructural changes within the granules of human mast cells (HMC-1) and increases their histamine content. Therefore, we hypothesized that NaBu treatment would also modify the storage of polysaccharides such as GAGs. NaBu (1 mM) significantly increased GAG content and granularity in a time- and concentration-dependent manner without affecting cell viability and metabolic activity. NaBu increased the expression of enzymes associated with heparin biosynthesis (GLCE, NDST1, NDST2, HS6ST1, and GALT1) in a time-dependent manner. A cholesteryl butyrate emulsion (CholButE) increased heparin content after 24 and 48 h and modestly altered the expression of genes involved in heparin biosynthesis. Similar to NaBu, CholButE reduced cell proliferation without significantly altering viability or metabolic activity. These data show that butyrate increases the synthesis and storage of heparin in human mast cells, perhaps by altering their metabolic pathways.
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Heparina , Mastocitos , Humanos , Mastocitos/metabolismo , Mastocitos/efectos de los fármacos , Heparina/farmacología , Heparina/metabolismo , Supervivencia Celular/efectos de los fármacos , Butiratos/farmacología , Butiratos/metabolismo , Proliferación Celular/efectos de los fármacos , Ácido Butírico/farmacología , Línea Celular , Ésteres del Colesterol/metabolismoRESUMEN
Postbiotics could exert different metabolic activities in animal models of non-alcoholic fatty liver disease (NAFLD) and in humans affected by metabolic syndrome. This is a randomized, double-blind, placebo-controlled, parallel-group clinical trial that enrolled a sample of 50 Caucasian healthy individuals with NAFLD, defined as liver steatosis, and metabolic syndrome. After a 4-week run-in, the enrolled individuals were randomized to take a food for special medical purposes with functional release, one tablet a day, containing calcium butyrate (500 mg/tablet), zinc gluconate (zinc 5 mg/tablet), and vitamin D3 (500 IU/tablet), or an identical placebo for 3 months. Liver and metabolic parameters were measured at baseline and at the end of the study. No subject experienced any adverse events during the trial. In both groups, a significant decrease in total cholesterol (TC) and triglycerides (TG) plasma levels was observed at the randomization visit vs. pre-run-in visit (p < 0.05). Regarding liver parameters, after treatment, the fatty liver index (FLI) improved significantly vs. baseline values (p < 0.05) and vs. placebo group (p < 0.05) in the active treatment group, and the hepatic steatosis index (HSI) improved significantly vs. baseline values (p < 0.05). Moreover, after active treatment, TC, TG, and gamma-glutamyl transferase (gGT) improved significantly vs. baseline values (p < 0.05), and TC and TG improved vs. placebo group (p < 0.05), as well. In the placebo group, liver parameters remained unchanged after treatment; only TG improved significantly vs. baseline values (p < 0.05). In our study, we observed that the butyrate-based formula improved FLI and plasma lipid patterns in individuals affected by liver steatosis and metabolic syndrome.
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Butiratos , Suplementos Dietéticos , Síndrome Metabólico , Enfermedad del Hígado Graso no Alcohólico , Humanos , Método Doble Ciego , Síndrome Metabólico/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Adulto , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Triglicéridos/sangre , Hígado/metabolismo , Hígado/efectos de los fármacos , Colesterol/sangre , Gluconatos/administración & dosificación , Resultado del TratamientoRESUMEN
Group 2 innate lymphoid cells (ILC2) strongly modulate COPD pathogenesis. However, the significance of microbiota in ILC2s remains unelucidated. Herein, we investigated the immunomodulatory role of short-chain fatty acids (SCFAs) in regulating ILC2-associated airway inflammation and explores its associated mechanism in COPD. In particular, we assessed the SCFA-mediated regulation of survival, proliferation, and cytokine production in lung sorted ILC2s. To elucidate butyrate action in ILC2-driven inflammatory response in COPD models, we administered butyrate to BALB/c mice via drinking water. We revealed that SCFAs, especially butyrate, derived from dietary fiber fermentation by gut microbiota inhibited pulmonary ILC2 functions and suppressed both IL-13 and IL-5 synthesis by murine ILC2s. Using in vivo and in vitro experimentation, we validated that butyrate significantly ameliorated ILC2-induced inflammation. We further demonstrated that butyrate suppressed ILC2 proliferation and GATA3 expression. Additionally, butyrate potentially utilized histone deacetylase (HDAC) inhibition to enhance NFIL3 promoter acetylation, thereby augmenting its expression, which eventually inhibited cytokine production in ILC2s. Taken together, the aforementioned evidences demonstrated a previously unrecognized role of microbial-derived SCFAs on pulmonary ILC2s in COPD. Moreover, our evidences suggest that metabolomics and gut microbiota modulation may prevent lung inflammation of COPD.
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Butiratos , Fibras de la Dieta , Linfocitos , Ratones Endogámicos BALB C , Enfermedad Pulmonar Obstructiva Crónica , Animales , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Ratones , Butiratos/farmacología , Linfocitos/metabolismo , Fibras de la Dieta/farmacología , Fibras de la Dieta/uso terapéutico , Ácidos Grasos Volátiles/metabolismo , Inflamación/metabolismo , Microbioma Gastrointestinal , Masculino , Citocinas/metabolismo , Humanos , Factor de Transcripción GATA3/metabolismoAsunto(s)
Benzoxazoles , Pie Diabético , Gangrena , Humanos , Pie Diabético/tratamiento farmacológico , Pie Diabético/complicaciones , Gangrena/etiología , Benzoxazoles/uso terapéutico , Butiratos/farmacología , Butiratos/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Metabolites resulting from the bacterial fermentation of dietary fibers, such as short-chain fatty acids, especially butyrate, play important roles in maintaining gut health and regulating various biological effects in the skin. However, butyrate is underutilized due to its unpleasant odor. To circumvent this organoleptic unfavorable property, phenylalanine butyramide (PBA), a butyrate precursor, has been synthesized and is currently available on the market. We evaluated the inhibition of mushroom tyrosinase by butyrate and PBA through in vitro assays, finding IC50 values of 34.7 mM and 120.3 mM, respectively. Docking calculations using a homology model of human tyrosinase identified a putative binding mode of PBA into the catalytic site. The anti-aging and anti-spot efficacy of topical PBA was evaluated in a randomized, double-blind, parallel-arm, placebo-controlled clinical trial involving 43 women affected by photo-damage. The results of this study showed that PBA significantly improved skin conditions compared to the placebo and was well tolerated. Specifically, PBA demonstrated strong skin depigmenting activity on both UV and brown spots (UV: -12.7% and -9.9%, Bs: -20.8% and -17.7% after 15 and 30 days, respectively, p < 0.001). Moreover, PBA brightened and lightened the skin (ITA°: +12% and 13% after 15 and 30 days, respectively, p < 0.001). Finally, PBA significantly improved skin elasticity (Ua/Uf: +12.4% and +32.3% after 15 and 30 days, respectively, p < 0.001) and firmness (Uf: -3.2% and -14.9% after 15 and 30 days, respectively, p < 0.01).
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Monofenol Monooxigenasa , Fenilalanina , Envejecimiento de la Piel , Pigmentación de la Piel , Adulto , Femenino , Humanos , Persona de Mediana Edad , Agaricales/enzimología , Butiratos/química , Butiratos/farmacología , Método Doble Ciego , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Simulación del Acoplamiento Molecular , Monofenol Monooxigenasa/antagonistas & inhibidores , Fenilalanina/química , Fenilalanina/análogos & derivados , Fenilalanina/farmacología , Envejecimiento de la Piel/efectos de los fármacos , Pigmentación de la Piel/efectos de los fármacosRESUMEN
BACKGROUND: The regulation of the circadian clock genes, which coordinate the activity of the immune system, is disturbed in inflammatory bowel disease (IBD). Emerging evidence suggests that butyrate, a short-chain fatty acid produced by the gut microbiota is involved in the regulation of inflammatory responses as well as circadian-clock genes. This study was conducted to investigate the effects of sodium-butyrate supplementation on the expression of circadian-clock genes, inflammation, sleep and life quality in active ulcerative colitis (UC) patients. METHODS: In the current randomized placebo-controlled trial, 36 active UC patients were randomly divided to receive sodium-butyrate (600 mg/kg) or placebo for 12-weeks. In this study the expression of circadian clock genes (CRY1, CRY2, PER1, PER2, BMAl1 and CLOCK) were assessed by real time polymerase chain reaction (qPCR) in whole blood. Gene expression changes were presented as fold changes in expression (2^-ΔΔCT) relative to the baseline. The faecal calprotectin and serum level of high-sensitivity C-reactive protein (hs-CRP) were assessed by enzyme-linked immunosorbent assay method (ELIZA). Moreover, the sleep quality and IBD quality of life (QoL) were assessed by Pittsburgh sleep quality index (PSQI) and inflammatory bowel disease questionnaire-9 (IBDQ-9) respectively before and after the intervention. RESULTS: The results showed that sodium-butyrate supplementation in comparison with placebo significantly decreased the level of calprotectin (-133.82 ± 155.62 vs. 51.58 ± 95.57, P-value < 0.001) and hs-CRP (-0.36 (-1.57, -0.05) vs. 0.48 (-0.09-4.77), P-value < 0.001) and upregulated the fold change expression of CRY1 (2.22 ± 1.59 vs. 0.63 ± 0.49, P-value < 0.001), CRY2 (2.15 ± 1.26 vs. 0.93 ± 0.80, P-value = 0.001), PER1 (1.86 ± 1.77 vs. 0.65 ± 0.48, P-value = 0.005), BMAL1 (1.85 ± 0.97 vs. 0.86 ± 0.63, P-value = 0.003). Also, sodium-butyrate caused an improvement in the sleep quality (PSQI score: -2.94 ± 3.50 vs. 1.16 ± 3.61, P-value < 0.001) and QoL (IBDQ-9: 17.00 ± 11.36 vs. -3.50 ± 6.87, P-value < 0.001). CONCLUSION: Butyrate may be an effective adjunct treatment for active UC patients by reducing biomarkers of inflammation, upregulation of circadian-clock genes and improving sleep quality and QoL.
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Colitis Ulcerosa , Suplementos Dietéticos , Calidad del Sueño , Humanos , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/genética , Colitis Ulcerosa/metabolismo , Masculino , Femenino , Adulto , Método Doble Ciego , Persona de Mediana Edad , Inflamación/genética , Inflamación/tratamiento farmacológico , Proteína C-Reactiva/metabolismo , Proteína C-Reactiva/genética , Calidad de Vida , Relojes Circadianos/genética , Relojes Circadianos/efectos de los fármacos , Complejo de Antígeno L1 de Leucocito/genética , Complejo de Antígeno L1 de Leucocito/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Butiratos , Ácido ButíricoRESUMEN
Given the significance of the intrauterine lipid environment in glucose metabolic homeostasis in offspring, the present study was undertaken to investigate the feasibility and efficacy of pemafibrate, a triglyceride-lowering peroxisome proliferator-activated agent, for maternal high-fat diet (HFD) intake-induced glucose metabolic dysfunction in offspring. A mouse model of HFD-induced gestational obesity was employed, and pemafibrate was orally administered from day 10 of gestation until delivery. The influences of maternal pemafibrate treatment on biological processes and toxicity were evaluated in both newborns and 12-week-old offspring. The findings of a dose-dependent decrease of ß cell islet mass and of impairment of glucose tolerance and insulin sensitivity in offspring suggest that maternal pemafibrate intervention can prevent maternal HFD-intake-induced diabetes in offspring. Of particular interest in the prevention of future glucose metabolic dysfunction in offspring, low-dose maternal pemafibrate treatment (0.02 mg/kg/day) had sufficient efficacy and appeared to be safe in offspring. Therefore, pemafibrate may be a potential agent for the prevention of maternal high-fat exposure-induced diabetes in offspring. Abbreviations: CD, control diet; DEG, differentially expressed genes; GTT, glucose tolerance test; HFD, high-fat diet; ITT, insulin tolerance test; MC, 0.5w/v% methyl cellulose 400 solution; PPAR, triglyceride-lowering peroxisome proliferator-activated receptor; RNA-seq, RNA sequencing; TC, total cholesterol; TG, triglycerides.
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Benzoxazoles , Butiratos , Dieta Alta en Grasa , Animales , Femenino , Dieta Alta en Grasa/efectos adversos , Embarazo , Butiratos/farmacología , Ratones , Benzoxazoles/farmacología , Benzoxazoles/administración & dosificación , Efectos Tardíos de la Exposición Prenatal/prevención & control , Efectos Tardíos de la Exposición Prenatal/metabolismo , Masculino , Estudios de Factibilidad , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Ratones Endogámicos C57BL , Resistencia a la Insulina/fisiología , Animales Recién NacidosRESUMEN
Chemotherapy-induced mucositis (CIM) is the typical side effect of chemotherapy. This study investigates the potential of alginate oligosaccharide (AOS) in ameliorating CIM induced by 5-fluorouracil (5-FU) in a murine model and its underlying mechanisms. AOS effectively mitigated body weight loss and histopathological damage, modulated inflammatory cytokines and attenuated the oxidative stress. AOS restored intestinal barrier integrity through enhancing expression of tight junction proteins via MLCK signaling pathway. AOS alleviated intestinal mucosal damage by inhibiting TLR4/MyD88/NF-κB signaling pathway, downregulating the pro-apoptotic protein Bax and upregulating the anti-apoptotic protein Bcl-2. Moreover, AOS significantly enriched intestinal Akkermansiaceae and increased the production of short-chain fatty acids (SCFAs), most notably butyrate and isovalerate. Pre-treatment with butyrate and isovalerate also alleviated 5-FU-induced CIM. In conclusion, AOS effectively mitigated CIM through strenghthening intestinal barrier, attenuating inflammation, and modulating gut microbiota and intestianl levels of butyrate and isovalerate. These finding indicate that AOS could be potentially utilized as a supplemental strategy for prevention or mitigation of CIM.
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Alginatos , Butiratos , Fluorouracilo , Mucosa Intestinal , Mucositis , Oligosacáridos , Fluorouracilo/efectos adversos , Animales , Mucositis/inducido químicamente , Mucositis/tratamiento farmacológico , Mucositis/metabolismo , Mucositis/patología , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Ratones , Oligosacáridos/farmacología , Oligosacáridos/química , Butiratos/farmacología , Butiratos/metabolismo , Alginatos/farmacología , Alginatos/química , Microbioma Gastrointestinal/efectos de los fármacos , Masculino , Estrés Oxidativo/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Citocinas/metabolismoRESUMEN
Trilobolide and its analogues belong to the guaianolide type of sesquiterpene lactones, which are characteristic and widely distributed within the families Asteraceae and Apiaceae. Certain guaianolides are receiving continuously increasing attention for their promising sarco-endoplasmic reticulum Ca2+-ATPase (SERCA)-inhibitory activity. However, because of their alkylation capabilities, they are generally toxic. Therefore, the search for compounds with significant immunobiological properties but with decreased cytotoxicities suitable for use in immune-based pharmacotherapy is ongoing. Therefore, we extended our previous investigation of the immunobiological effects of trilobolide to a series of structurally related guaianolides and germacranolides. To evaluate the relationship, we tested a series of selected derivatives containing α-methyl lactone or exomethylene lactone ring. For a wider comparison, we also included some of their glycosidic derivatives. We assessed the in vitro immunobiological effects of the tested compounds on nitric oxide (NO) production, cytokine secretion, and prostaglandin E2 (PGE2) release by mouse peritoneal cells, activated primarily by lipopolysaccharide (LPS), and evaluated their viability. The inhibitory effects of the apparently most active substance, 8-deoxylactucin, seem to be the most promising.
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Lactonas , Óxido Nítrico , Sesquiterpenos de Germacrano , Sesquiterpenos de Guayano , Animales , Óxido Nítrico/metabolismo , Ratones , Sesquiterpenos de Germacrano/farmacología , Sesquiterpenos de Germacrano/química , Sesquiterpenos de Guayano/farmacología , Sesquiterpenos de Guayano/química , Lactonas/farmacología , Lactonas/química , Lipopolisacáridos/farmacología , Sesquiterpenos/farmacología , Sesquiterpenos/química , Citocinas/metabolismo , Dinoprostona/metabolismo , Dinoprostona/biosíntesis , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/metabolismo , Butiratos , FuranosRESUMEN
Interventions involving dietary fibers are known to benefit host health. A leading contribution of gut microbiota is commonly recognized with production of short chain fatty acids (SCFA) suspected to play a key role. However, the detailed mechanisms are largely unknown, and apart from a well-described bifidogenic effect of some fibers, results for other bacterial taxa are often incongruent between studies. We performed pooled analyses of 16S rRNA gene data derived from intervention studies (n = 14) based on three fibers, namely, inulin-type fructans (ITF), resistant starch (RS), and arabinoxylan-oligosaccharides (AXOS), harmonizing the bioinformatics workflow to reveal taxa stimulated by those substrates, specifically focusing on the SCFA-production potential. The results showed an increased butyrate production potential after ITF (p < 0.05) and RS (p < 0.1) treatment via an increase in bacteria exhibiting the enzyme butyryl-CoA:acetate CoA-transferase (but) that was governed by Faecalibacterium, Anaerostipes (ITF) and Agathobacter (RS) respectively. AXOS did not promote an increase in butyrate producers, nor were pathways linked to propionate production stimulated by any intervention. A bifidogenic effect was observed for AXOS and ITF, which was only partly associated with the behavior of but-containing bacteria and largely represented a separate response. Low and high Ruminococcus abundances pre-intervention for ITF and RS, respectively, promoted an increase in but-containing taxa (p < 0.05) upon interventions, whereas initial Prevotella abundance was negatively associated with responses of butyrate producers for both fibers. Collectively, our data demonstrate targeted stimulation of specific taxa by individual fibers increasing the potential to synthesize butyrate, where gut microbiota composition pre-intervention strongly controlled outcomes.
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Bacterias , Butiratos , Fibras de la Dieta , Microbioma Gastrointestinal , ARN Ribosómico 16S , Xilanos , Fibras de la Dieta/metabolismo , Butiratos/metabolismo , Xilanos/metabolismo , ARN Ribosómico 16S/genética , Bacterias/genética , Bacterias/clasificación , Bacterias/metabolismo , Humanos , Coenzima A Transferasas/genética , Coenzima A Transferasas/metabolismo , Ácidos Grasos Volátiles/metabolismo , Inulina/metabolismo , Almidón/metabolismo , Oligosacáridos/metabolismo , Faecalibacterium/genética , Biología Computacional/métodosRESUMEN
Nanogels offer hope for precise drug delivery, while addressing drug delivery hurdles is vital for effective prostate cancer (PCa) management. We developed an injectable elastin nanogels (ENG) for efficient drug delivery system to overcome castration-resistant prostate cancer (CRPC) by delivering Decursin, a small molecule inhibitor that blocks Wnt/ßcatenin pathways for PCa. The ENG exhibited favourable characteristics such as biocompatibility, flexibility, and low toxicity. In this study, size, shape, surface charge, chemical composition, thermal stability, and other properties of ENG were used to confirm the successful synthesis and incorporation of Decursin (DEC) into elastin nanogels (ENG) for prostate cancer therapy. In vitro studies demonstrated sustained release of DEC from the ENG over 120 h, with a pH-dependent release pattern. DU145 cell line induces moderate cytotoxicity of DEC-ENG indicates that nanomedicine has an impact on cell viability and helps strike a balance between therapeutics efficacy and safety while the EPR effect enables targeted drug delivery to prostate tumor sites compared to free DEC. Morphological analysis further supported the effectiveness of DEC-ENG in inducing cell death. Overall, these findings highlight the promising role of ENG-encapsulated decursin as a targeted drug delivery system for CRPC.
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Elastina , Nanogeles , Neoplasias de la Próstata Resistentes a la Castración , Masculino , Elastina/química , Humanos , Línea Celular Tumoral , Nanogeles/química , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/patología , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Sistemas de Liberación de Medicamentos , Supervivencia Celular/efectos de los fármacos , Liberación de Fármacos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/administración & dosificación , Benzopiranos , ButiratosRESUMEN
BACKGROUND: Selenium (Se) is a rare essential element that plays a vital role in the health and performance of animals. By interfering in the production of antioxidant enzymes such as glutathione peroxidase, thioredoxin reductase and methionine sulfoxide, Se plays a role in reducing the effects of oxidative stress and animal performance. OBJECTIVES: This study aimed to investigate the effect of hydroxy-selenomethionine (OH-SeMet) in the diet of broiler breeder and old broiler breeder roosters on productive performance, reproduction and sperm quality parameters. METHODS: For this purpose, 260 broiler breeders of the Ross 308 strain were used in a completely randomized design with four treatments and five replications (13 hens and one rooster in each replication). Experimental treatments included: (1) a basal diet without OH-SeMet (T1:control), (2) a broiler breeder diet without OH-SeMet and a rooster diet containing 0.1 mg/kg OH-SeMet (T2), (3) broiler breeder diet containing 0.1 mg/kg OH-SeMet and rooster diet without OH-SeMet (T3) and (4) broiler breeder and rooster diet contained 0.1 mg/kg OH-SeMet (T4). RESULTS: The results showed that T3 and T4 treatments improved egg production, egg weight, egg mass and feed conversion ratio (FCR) compared to the control treatment (p < 0.05). The fertility and hatchability percentages of T4 and T2 treatments increased compared to T1 and T3 treatments (p < 0.05). The rate of embryonic losses in T1 was higher than in other treatments. However, grade one chickens were higher in T4 than in other treatments (p < 0.05). Total motility and viability of sperms were significantly higher in T2 and T4 treatments than in T1 and T3 treatments. The sperm abnormality percentage and sperm MDA concentration decreased in T2 and T4 treatments. CONCLUSIONS: Therefore, using OH-SeMet may be a practical approach to help old broiler breeders' production and reproduction performance.
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Alimentación Animal , Pollos , Dieta , Suplementos Dietéticos , Reproducción , Selenometionina , Animales , Pollos/fisiología , Selenometionina/farmacología , Selenometionina/administración & dosificación , Dieta/veterinaria , Masculino , Alimentación Animal/análisis , Femenino , Suplementos Dietéticos/análisis , Reproducción/efectos de los fármacos , Distribución Aleatoria , Butiratos , Compuestos de SelenioRESUMEN
Newborn piglets' health is seriously threatened by the porcine epidemic diarrhea virus (PEDV), which also has a significant effect on the pig industry. The gut microbiota produces butyrate, an abundant metabolite that modulates intestinal function through many methods to improve immunological and intestinal barrier function. The objective of this investigation was to ascertain how elevated butyrate concentrations impacted the host transcriptional profile of PEDV CV777 strain infection. Our findings showed that higher concentrations of butyrate have a stronger inhibitory effect on PEDV CV777 strain infection. According to RNA-seq data, higher concentrations of butyrate induced more significant transcriptional changes in IPEC-J2 cells, and signaling pathways such as PI3K-AKT may play a role in the inhibition of PEDV CV777 strain by high concentrations of butyrate. Ultimately, we offer a theoretical and experimental framework for future research and development of novel approaches to harness butyrate's antiviral infection properties.
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Butiratos , Células Epiteliales , Virus de la Diarrea Epidémica Porcina , Animales , Virus de la Diarrea Epidémica Porcina/efectos de los fármacos , Virus de la Diarrea Epidémica Porcina/fisiología , Porcinos , Butiratos/farmacología , Butiratos/metabolismo , Células Epiteliales/virología , Células Epiteliales/efectos de los fármacos , Línea Celular , Enfermedades de los Porcinos/virología , Infecciones por Coronavirus/virología , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/veterinaria , Antivirales/farmacología , Transducción de Señal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/virología , Mucosa Intestinal/efectos de los fármacos , Replicación Viral/efectos de los fármacos , Intestinos/virologíaRESUMEN
Emerging evidence indicates that gut dysbiosis is involved in the pathogenesis of visceral hypersensitivity (VH). However, how gut microbiota contributes to the development of VH is unknown. Here, we sought to examine the signal transduction pathways from gut to dorsal root ganglion (DRG) responsible for this. Therefore, abdominal withdrawal reflex (AWR) scores, fecal output, fecal water content, and total gastrointestinal transit time (TGITT) were assessed in Con rats, VH rats, rats treated with NaB, and VH rats treated with VSL#3. Fecal microbiota and its metabolite (short-chain fatty acids, SCFAs), mast cell degranulation in colon, lincRNA-01028, miR-143, and protease kinase C (PKC) and TRPV1 expression in DRGs were further detected. VH rats showed an increased fecal water content, a shortened TGITT, an increased abundance of Clostridium sensu stricto 1 and increased butyrate in fecal samples, an increased mast cell degranulation, an increased expression of lincRNA-01028, PKC, and TRPV1, and a decreased expression of miR-143 in DRGs compared with control rats, which could be restored by the application of probiotic VSL#3. The above-mentioned detection in rats treated with butyrate was similar to that of VH rats. We further confirm whether butyrate sensitized DRG neurons by a lincRNA-01028, miR-143, and PKC-dependent mechanism via mast cell in vitro. In co-cultures, MCs treated with butyrate elicited a higher TRPV1 current, a higher expression of lincRNA-01028, PKC, and a lower expression of miR-143 in DRG neurons, which could be inhibited by a lincRNA-01028 inhibitor. These findings indicate that butyrate promotes visceral hypersensitivity via mast cell-derived DRG neuron lincRNA-01028-PKC-TRPV1 pathway.IMPORTANCEIrritable bowel syndrome (IBS), characterized by visceral hypersensitivity, is a common gastrointestinal dysfunction syndrome. Although the gut microbiota plays a role in the pathogenesis and treatment of irritable bowel syndrome (IBS), the possible underlying mechanisms are unclear. Therefore, it is of critical importance to determine the signal transduction pathways from gut to DRG responsible for this in vitro and in vivo assay. This study demonstrated that butyrate sensitized TRPV1 in DRG neurons via mast cells in vivo and in vitro by a lincRNA-01028, miR-143, and PKC-dependent mechanism. VH rats similarly showed an increased abundance of Clostridium sensu stricto 1, an increased fecal butyrate, an increased mast cell degranulation, and increased expression of TRPV1 compared with control rats, which could be restored by the application of VSL#3. In conclusion, butyrate produced by the altered intestinal microbiota is associated with increased VH.
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Butiratos , Modelos Animales de Enfermedad , Ganglios Espinales , Síndrome del Colon Irritable , Mastocitos , Proteína Quinasa C , Ratas Sprague-Dawley , Canales Catiónicos TRPV , Animales , Ganglios Espinales/metabolismo , Canales Catiónicos TRPV/metabolismo , Canales Catiónicos TRPV/genética , Ratas , Mastocitos/metabolismo , Mastocitos/efectos de los fármacos , Masculino , Butiratos/metabolismo , Butiratos/farmacología , Proteína Quinasa C/metabolismo , Síndrome del Colon Irritable/metabolismo , Síndrome del Colon Irritable/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Transducción de Señal , Neuronas/metabolismo , Neuronas/efectos de los fármacosRESUMEN
The gut microbiota is a diverse bacterial community consisting of approximately 2000 species, predominantly from five phyla: Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, and Verrucomicrobia. The microbiota's bacterial species create distinct compounds that impact the host's health, including well-known short-chain fatty acids. These are produced through the breakdown of dietary fibers and fermentation of undigested carbohydrates by the intestinal microbiota. The main short-chain fatty acids consist of acetate, propionate, and butyrate. The concentration of butyrate in mammalian intestines varies depending on the diet. Its main functions are use as an energy source, cell differentiation, reduction in the inflammatory process in the intestine, and defense against oxidative stress. It also plays an epigenetic role in histone deacetylases, thus helping to reduce the risk of colon cancer. Finally, butyrate affects the gut-brain axis by crossing the brain-blood barrier, making it crucial to determine the right concentrations for both local and peripheral effects. In recent years, there has been a significant amount of attention given to the role of dietary polyphenols and fibers in promoting human health. Polyphenols and dietary fibers both play crucial roles in protecting human health and can produce butyrate through gut microbiota fermentation. This paper aims to summarize information on the key summits related to the negative correlation between intestinal microbiota diversity and chronic diseases to guide future research on determining the specific activity of butyrate from polyphenols and dietary fibers that can carry out these vital functions.
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Butiratos , Fibras de la Dieta , Microbioma Gastrointestinal , Polifenoles , Microbioma Gastrointestinal/efectos de los fármacos , Fibras de la Dieta/metabolismo , Fibras de la Dieta/farmacología , Humanos , Polifenoles/farmacología , Butiratos/metabolismo , Animales , Ácidos Grasos Volátiles/metabolismo , FermentaciónRESUMEN
BACKGROUND: The intestinal-liver axis is associated with various liver diseases. Here, we verified the role of the gut microbiota and macrophage activation in the progression of pyrrolizidine alkaloids-induced hepatic sinusoidal obstruction syndrome (PA-HSOS), and explored the possible mechanisms and new treatment options. METHODS: The HSOS murine model was induced by gavage of monocrotaline (MCT). An analysis of 16S ribosomal DNA (16S rDNA) of the feces was conducted to determine the composition of the fecal microbiota. Macrophage clearance, fecal microbiota transplantation (FMT), and butyrate supplementation experiments were used to assess the role of intestinal flora, gut barrier, and macrophage activation and to explore the relationships among these three variables. RESULTS: Activated macrophages and low microflora diversity were observed in HSOS patients and murine models. Depletion of macrophages attenuated inflammatory reactions and apoptosis in the mouse liver. Moreover, compared with control-FMT mice, the exacerbation of severe liver injury was detected in HSOS-FMT mice. Specifically, butyrate fecal concentrations were significantly reduced in HSOS mice, and administration of butyrate could partially alleviated liver damage and improved the intestinal barrier in vitro and in vivo. Furthermore, elevated lipopolysaccharides in the portal vein and high proportions of M1 macrophages in the liver were also detected in HSOS-FMT mice and mice without butyrate treatment, which resulted in severe inflammatory responses and further accelerated HSOS progression. CONCLUSIONS: These results suggested that the gut microbiota exacerbated HSOS progression by regulating macrophage M1 polarization via altered intestinal barrier function mediated by butyrate. Our study has identified new strategies for the clinical treatment of HSOS.
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Butiratos , Modelos Animales de Enfermedad , Trasplante de Microbiota Fecal , Microbioma Gastrointestinal , Enfermedad Veno-Oclusiva Hepática , Hígado , Macrófagos , Animales , Ratones , Butiratos/metabolismo , Macrófagos/inmunología , Masculino , Humanos , Enfermedad Veno-Oclusiva Hepática/microbiología , Hígado/metabolismo , Activación de Macrófagos , Ratones Endogámicos C57BL , Mucosa Intestinal/microbiología , Femenino , Heces/microbiología , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/genética , Funcion de la Barrera IntestinalRESUMEN
Type-2 diabetes (T2D) is a rapidly growing multifactorial metabolic disorder that induces the onset of various diseases in the human body. The compositional and metabolic shift of the gut microbiota is a crucial factor behind T2D. Hence, gaining insight into the metabolic profile of the gut microbiota is essential for revealing their role in regulating the metabolism of T2D patients. Here, we have focused on the genome-scale community metabolic model reconstruction of crucial T2D-associated gut microbes. The model-based analysis of biochemical flux in T2D and healthy gut conditions showed distinct biochemical signatures and diverse metabolic interactions in the microbial community. The metabolic interactions encompass cross-feeding of short-chain fatty acids, amino acids, and vitamins among individual microbes within the community. In T2D conditions, a reduction in the metabolic flux of acetate, butyrate, vitamin B5, and bicarbonate was observed in the microbial community model, which can impact carbohydrate metabolism. The decline in butyrate levels is correlated with both insulin resistance and diminished glucose metabolism in T2D patients. Compared to the healthy gut, an overall reduction in glucose consumption and SCFA production flux was estimated in the T2D gut environment. Moreover, the decreased consumption profiles of branch chain amino acids (BCAAs) and aromatic amino acids (AAAs) in the T2D gut microbiota can be a distinct biomarker for T2D. Hence, the flux-level analysis of the microbial community model can provide insights into the metabolic reprogramming in diabetic gut microbiomes, which may be helpful in personalized therapeutics and diet design against T2D.