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1.
PLoS One ; 19(2): e0298148, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38363776

RESUMO

Sanhua decoction (SHD), a traditional prescription, has long been used in treating ischemic stroke (IS). However, the therapeutic effect of SHD and the associated changes in gut microbiota and short-chain fatty acids (SCFAs) are uncertain. In this study, a rat model of IS was established by the middle cerebral artery occlusion (MCAO). By evaluating the cerebral infarct area and brain tissue pathology, it was found that SHD ameliorated IS-related symptoms in MCAO rats. Using 16S rRNA gene sequencing, we found that SHD reduced abnormally elevated Lactobacillus and opportunistic pathogens such as Desulfovibrio, but increased some beneficial bacteria that produce SCFAs, including Clostridia, Lachnospiraceae, Ruminococcaceae, and Coprococcus. KEGG analysis revealed that SHD regulates several pathways, including D-arginine and D-ornithine metabolism, polyketide sugar unit biosynthesis, and cyanoamino acid metabolism, which are significantly altered in MCAO rats. By gas chromatography-mass spectrometry detection of SCFAs, we found that fecal acetic acid, valeric acid, and caproic acid were significantly increased in MCAO rats, whereas propionic acid and isobutyric acid were decreased. SHD reversed the changes in acetic acid and propionic acid in the model rats and significantly increased fecal butyric acid. In addition, MCAO rats had significantly higher serum levels of acetic acid, butyric acid, isovaleric acid, and valeric acid, and lower levels of caproic acid. Altered serum levels of butyric acid, isovaleric acid, valeric acid, and caproic acid were restored, and the level of isobutyric acid was reduced after SHD administration. Spearman analysis revealed that cerebral infarct area had a strong correlation with Bifidobacterium, Desulfovibrio, Lachnospiraceae, Lactobacillus, acetic acid, valeric acid, and caproic acid. Overall, this study demonstrates for the first time that the effect of SHD on IS may be related to gut microbiota and SCFAs, providing a potential scientific explanation for the ameliorative effect of SHD on IS.


Assuntos
Microbioma Gastrointestinal , Hemiterpenos , Ácidos Pentanoicos , Propionatos , Ratos , Animais , Caproatos , Microbioma Gastrointestinal/fisiologia , Isobutiratos , Infarto da Artéria Cerebral Média/tratamento farmacológico , RNA Ribossômico 16S , Ácidos Graxos Voláteis/metabolismo , Ácido Acético , Ácido Butírico/farmacologia
2.
Molecules ; 29(2)2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38257306

RESUMO

Hepatocellular carcinoma (HCC), one of the most common malignant cancers with a low 5-year survival rate, is the third leading cause of cancer-related deaths worldwide. The finding of novel agents and strategies for the treatment of HCC is an urgent need. Sesquiterpene lactones (SLs) have attracted extensive attention because of their potent antitumor activity. In this study, a new series of SL derivatives (3-18) were synthesized using epimers 1 and 2 as parent molecules, isolated from Sphagneticola trilobata, and evaluated for their anti-HCC activity. Furthermore, the structures of 4, 6, and 14 were confirmed by X-ray single-crystal diffraction analyses. The cytotoxic activities of 3-18 on two HCC cell lines, including HepG2 and Huh7, were evaluated using the CCK-8 assay. Among them, compound 10 exhibited the best activity against the HepG2 and Huh7 cell lines. Further studies showed that 10 induced cell apoptosis, arrested the cell cycle at the S phase, and induced the inhibition of cell proliferation and migration in HepG2 and Huh7. In addition, absorption, distribution, metabolism, and excretion (ADME) properties prediction showed that 10 may possess the properties to be a drug candidate. Thus, 10 may be a promising lead compound for the treatment of HCC.


Assuntos
Butiratos , Carcinoma Hepatocelular , Furanos , Neoplasias Hepáticas , Sesquiterpenos , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Isobutiratos , Neoplasias Hepáticas/tratamento farmacológico , Sesquiterpenos/farmacologia , Lactonas/farmacologia
3.
Microb Biotechnol ; 17(1): e14321, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37649327

RESUMO

Clostridium luticellarii is a recently discovered acetogen that is uniquely capable of producing butyric and isobutyric acid from various substrates (e.g. methanol), but it is unclear which factors influence its (iso)butyric acid production from H2 and CO2 . We aimed to investigate the autotrophic metabolism of C. luticellarii by identifying the necessary growth conditions and examining the effects of pH and metabolite levels on product titers and selectivity. Results show that autotrophic growth of C. luticellarii requires the addition of complex nutrient sources and the absence of shaking conditions. Further experiments combined with thermodynamic calculations identified pH as a key parameter governing the direction of metabolic fluxes. At circumneutral pH (~6.5), acetic acid is the sole metabolic end product but C. luticellarii possesses the unique ability to co-oxidize organic acids such as valeric acid under high H2 partial pressures (>1 bar). Conversely, mildly acidic pH (≤5.5) stimulates the production of butyric and isobutyric acid while partly halting the oxidation of organic acids. Additionally, elevated acetic acid concentrations stimulated butyric and isobutyric acid production up to a combined selectivity of 53 ± 3%. Finally, our results suggest that isobutyric acid is produced by a reversible isomerization of butyric acid, but valeric and caproic acid are not isomerized. These combined insights can inform future efforts to optimize and scale-up the production of valuable chemicals from CO2 using C. luticellarii.


Assuntos
Dióxido de Carbono , Clostridium , Isobutiratos , Ácido Butírico/metabolismo , Ácido Acético , Fermentação
4.
Pest Manag Sci ; 80(2): 355-365, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37691614

RESUMO

BACKGROUND: Hippodamia variegata (Goeze) (Coleoptera: Coccinellidae), a dominant predatory natural enemy species in cotton-planting, is a key biological control agent for aphids in China. Our previous study showed that herbivore-induced plant volatiles (HIPVs) from Glycyrrhiza uralensis (Fisch.) (Fabales: Fabaceae) and Alhagi sparsifolia (Desv.) (Fabales: Fabaceae) plants infested with Aphis atrata (Zhang) (Homoptera: Aphididae), were important semiochemicals for Hippodamia variegata to locate aphids. However, little was known about the varieties and function of active volatiles from HIPVs of the two plant species. RESULTS: In this study, results from gas chromatography-electroantennography detection (GC-EAD) demonstrated that seven HIPVs (butyl acrylate, α-pinene, butyl isobutyrate, ß-pinene, butyl butyrate, 1,3-diethylbenzene and 1,4-diethylbenzene) identified from the two damaged plant species elicited antennal responses from Hippodamia variegata. Also, results from gas chromatograph-mass spectrometry (GC-MS) analysis showed that the concentrations of the seven active volatiles were significantly higher than those from corresponding healthy plants. Hippodamia variegata exhibited varying degrees of response to each active volatile in electroantennography (EAG) trials, however, only α-pinene, butyl isobutyrate, ß-pinene and butyl butyrate significantly attracted Hippodamia variegata in behavioral trials conducted in the laboratory. They also had a better trapping effect on Hippodamia variegata in cotton fields. CONCLUSION: Four active compounds (α-pinene, butyl isobutyrate, ß-pinene and butyl butyrate) identified from two damaged plant species were considered the most effective HIPVs that attract Hippodamia variegata. These findings provide possibilities for the development of Hippodamia variegata attractants. They also provide a theoretical basis for the biological prevention and control of aphids using Hippodamia variegata. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Assuntos
Afídeos , Monoterpenos Bicíclicos , Butiratos , Besouros , Fabaceae , Glycyrrhiza uralensis , Animais , Afídeos/fisiologia , Isobutiratos , Cromatografia Gasosa-Espectrometria de Massas
5.
Sheng Wu Gong Cheng Xue Bao ; 39(12): 4927-4938, 2023 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-38147992

RESUMO

In order to investigate the enzyme production mechanism of yak rumen-derived anaerobic fungus Orpinomyces sp. YF3 under the induction of different carbon sources, anaerobic culture tubes were used for in vitro fermentation. 8 g/L of glucose (Glu), filter paper (Flp) and avicel (Avi) were respectively added to 10 mL of basic culture medium as the sole carbon source. The activity of fiber-degrading enzyme and the concentration of volatile fatty acid in the fermentation liquid were detected, and the enzyme producing mechanism of Orpinomyces sp. YF3 was explored by transcriptomics. It was found that, in glucose-induced fermentation solution, the activities of carboxymethyl cellulase, microcrystalline cellulase, filter paper enzyme, xylanase and the proportion of acetate were significantly increased (P < 0.05), the proportion of propionate, butyrate, isobutyrate were significantly decreased (P < 0.05). The results of transcriptome analysis showed that there were 5 949 differentially expressed genes (DEGs) between the Glu group and the Flp group, 10 970 DEGs between the Glu group and the Avi group, and 6 057 DEGs between the Flp group and the Avi group. It was found that the DEGs associated with fiber degrading enzymes were significantly up-regulated in the Glu group. Gene ontology (GO) function enrichment analysis identified that DEGs were mainly associated with the xylan catabolic process, hemicellulose metabolic process, ß-glucan metabolic process, cellulase activity, endo-1,4-ß-xylanase activity, cell wall polysaccharide metabolic process, carbohydrate catabolic process, glucan catabolic process and carbohydrate metabolic process. Moreover, the differentially expressed pathways associated with fiber degrading enzymes enriched by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were mainly starch and sucrose metabolic pathways and other glycan degradation pathways. In conclusion, Orpinomyces sp. YF3 with glucose as carbon source substrate significantly increased the activity of cellulose degrading enzyme and the proportion of acetate, decreased the proportion of propionate, butyrate and isobutyrate. Furthermore, the degradation ability and energy utilization efficiency of fungus in the presence of glucose were improved by means of regulating the expression of cellulose degrading enzyme gene and participating in starch and sucrose metabolism pathway, and other glycan degradation pathways, which provides a theoretical basis for the application of Orpinomyces sp. YF3 in practical production and facilitates the application of Orpinomyces sp. YF3 in the future.


Assuntos
Celulase , Celulases , Neocallimastigales , Animais , Bovinos , Neocallimastigales/metabolismo , Anaerobiose , Rúmen/microbiologia , Propionatos/metabolismo , Isobutiratos/metabolismo , Celulose/metabolismo , Fungos , Amido/metabolismo , Glucose/metabolismo , Acetatos , Sacarose/metabolismo
6.
Lipids Health Dis ; 22(1): 164, 2023 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-37789460

RESUMO

BACKGROUND: Urinary 3-indoxyl sulfate levels as well as fecal short chain fatty acid (SCFA) concentrations are surrogate markers for gut microbiota diversity. Patients with inflammatory bowel diseases (IBDs) and patients with primary sclerosing cholangitis (PSC), a disease closely associated with IBD, have decreased microbiome diversity. In this paper, the fecal SCFAs propionate, acetate, butyrate and isobutyrate of patients with IBD and patients with PSC-IBD and urinary 3-indoxyl sulfate of IBD patients were determined to study associations with disease etiology and severity. METHODS: SCFA levels in feces of 64 IBD patients and 20 PSC-IBD patients were quantified by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Urinary 3-indoxyl sulfate levels of 45 of these IBD patients were analysed by means of reversed-phase liquid chromatography-electrospray ionization-tandem mass spectrometry. Feces of 17 healthy controls and urine of 13 of these controls were analyzed in parallel. These cohorts had comparable sex distribution and age. RESULTS: Urinary 3-indoxyl sulfate concentrations (normalized to urinary creatinine levels) was increased (P = 0.030) and fecal isobutyrate levels (normalized to dry weight of the stool sample) of IBD patients were decreased (P = 0.035) in comparison to healthy controls. None of the analyzed metabolites differed between patients with Crohn´s disease (CD) and patients with ulcerative colitis (UC). Fecal acetate and butyrate positively correlated with fecal calprotectin (P = 0.040 and P = 0.005, respectively) and serum C-reactive protein (P = 0.024 and P = 0.025, respectively) in UC but not CD patients. UC patients with fecal calprotectin levels above 150 µg/g, indicating intestinal inflammatory activity, had higher fecal acetate (P = 0.016), butyrate (P = 0.007) and propionate (P = 0.046) in comparison to patients with fecal calprotectin levels < 50 µg/g. Fecal SCFA levels of PSC-IBD and IBD patients were comparable. CONCLUSIONS: Current findings suggest that analysis of urinary 3-indoxyl-sulfate as well as fecal SCFAs has no diagnostic value for IBD and PSC-IBD diagnosis or monitoring of disease severity.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Colite Ulcerativa/diagnóstico , Doença de Crohn/diagnóstico , Indicã/análise , Isobutiratos/análise , Propionatos , Cromatografia Líquida , Espectrometria de Massas em Tandem , Ácidos Graxos Voláteis/metabolismo , Biomarcadores/análise , Butiratos , Acetatos/análise , Gravidade do Paciente , Fezes/química , Complexo Antígeno L1 Leucocitário/análise
7.
Zhen Ci Yan Jiu ; 48(9): 881-9, 2023 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-37730258

RESUMO

OBJECTIVE: To explore the mechanism of moxibustion in the treatment of asthmatic inflammation from the point of short-chain fatty acids (SCFAs) in rats with asthma. METHODS: A total of 48 SD rats (half male and half female) were randomly divided into 4 groups: normal, model, lung treatment and joint-treatment of lung and intestine (joint-treatment), with 12 rats in each group. The asthma model was made by subcutaneous (bilateral back and inguinal regions) and intraperitoneal injection of mixture solution of ovalbumin and aluminium hydroxide gel (on day 1 and 8) and followed by inhalation of atomized 1% ovalbumin (20 min from day 15, once daily for one week). Moxibustion was applied to bilateral "Feishu" (BL13) for rats of the lung treatment group or bilateral "Feishu" (BL13) and "Tianshu" (ST25) for rats of the joint treatment group. One hour after the intervention, the rats in the later three groups were separately given atomized 1% ovalbumin solution inhalation for 20 min. The treatment was conducted for 30 min, once daily for 14 consecutive days. At the end of the intervention, the percentage of inflammatory cells in blood was detected by biochemical method and histopathological changes of the lung were observed after H.E. staining. The inflammatory cells in the bronchoalveolar lavage fluid (BALF) were counted after Wright-Giemsa staining. The mRNA expressions of interleukin (IL)-4, IL-5, IL-13, IL-17, IL-33, leukotriene (LT), thymic stromal lymphopoietin (TSLP) and prostaglandin D2 (PGD2) were detected by real-time PCR, and the contents of SCFAs in rats' feces were detected by gas chromatography-mass spectrometry. RESULTS: Relevant to the normal group, the model group had an obvious increase in the percentages of neutrophils, lymphocytes and eosinophils in the blood, the percentages of neutrophils and eosinophils in the BALF, and in the expression levels of PGD2, TSLP, LT, IL-4, IL-5, IL-13, IL-17 and IL-33 mRNAs in the lung tissues (P<0.01, P<0.05), and a marked decrease in the contents of acetic acid, propionic acid, isobutyric acid, butyric acid and valeric acid in feces (P<0.05, P<0.01). After the treatment, the percentages of neutrophils and lymphocytes in the peripheral blood, eosinophils in the BALF, and the expression levels of PGD2, TSLP, LT, IL-4, IL-17, IL-33 mRNAs in the lung tissues in both the lung treatment and joint treatment groups, as well as neutrophils of BALF, and expression of IL-5 and IL-13 mRNAs in the joint treatment group were significantly down-regulated (P<0.01, P<0.05), while the contents of acetic acid, propionic acid and valerate in the lung treatment group, and acetic acid, propionic acid, isobutyric acid, butyric acid and valeric acid in the joint treatment group were all strikingly increased (P<0.05, P<0.01). The effect of the joint treatment was superior to that of lung treatment in down-regulating the expressions of LT and IL-5 mRNAs (P<0.05, P<0.01) and up-requlating the content of propionic acid (P<0.05). Results of H.E. staining showed thickened alveolar wall, infiltration of a large number of inflammatory cells and interstitial fibrous tissue hyperplasia around the bronchus and scattered arrangement of cells of the lung tissue in the model group, which was relatively milder in both lung treatment and joint treatment groups, particularly the later. CONCLUSION: Joint treatment of asthma from the lung and intestine can better regulate the contents of intestinal SCFAs and alleviate the inflammatory response of asthmatic model rats, thus, intestinal SCFAs may be involved in the process of moxibustion in improving inflammatory response.


Assuntos
Asma , Moxibustão , Pneumonia , Animais , Feminino , Masculino , Ratos , Pontos de Acupuntura , Asma/genética , Asma/terapia , Ácidos Graxos Voláteis , Interleucina-13 , Interleucina-17 , Interleucina-33 , Interleucina-4 , Interleucina-5 , Intestinos , Isobutiratos , Pulmão , Ovalbumina , Propionatos , Prostaglandina D2 , Ratos Sprague-Dawley
8.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 45(4): 581-590, 2023 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-37654138

RESUMO

Objective To investigate the effects of Weidiao-3(WD-3)Mixture on the clinical efficacy of immunotherapy for advanced gastric cancer and the intestinal flora.Methods Fifty-one patients with advanced gastric cancer treated in Wuxi Traditional Chinese Medicine Hospital from January 2020 to December 2021 were randomized into a WD-3 group(immunotherapy + WD-3 Mixture,one dose per day)(n=25)and a gastric cancer(GC) group(only immunotherapy)(n=26)according to the admission time.Ten healthy volunteers were included as the healthy control group.The Karnofsky score and the Quality of Life Questionnare-Core score were evaluated before and after treatment,and the clinical efficacy was compared after treatment.After treatment,the stool samples were collected for 16SrRNA gene high-throughput sequencing and targeted metabolomics.The α and ß diversity and structure of the intestinal flora and the content of short-chain fatty acids were compared between groups.Results The quality of life in both groups improved after treatment and was better in the WD-3 group than in the GC group(P=0.035).The dry mouth(P=0.038)and altered taste(P=0.008)were mitigated in the WD-3 group after treatment,and the reflux(P=0.001)and dry mouth(P=0.022)were mitigated in the GC group after treatment.After treatment,the WD-3 group outperformed the GC group in terms of dysphagia(P=0.047)and dry mouth(P=0.045).The WD-3 group was superior to the GC group in terms of objective remission rate and disease control rate,with prolonged median progression-free survival and median overall survival(P=0.039,P=0.043).The α and ß diversity indexes of the intestinal flora showed no significant differences between WD-3 and GC groups(all P>0.05).At the phylum level,WD-3 and GC groups had lower relative abundance of Firmicutes(P=0.038,P=0.042)and higher relative abundance of Proteobacteria(P=0.016,P=0.015)than the healthy control group.The relative abundance of Actinomycetes in the GC group was lower than that in the healthy control group(P=0.035)and the WD-3 group(P=0.046).At the genus level,the GC group had lower relative abundance of Bifidobacteria and Coprococcus than the healthy control group and the WD-3 group(all P<0.001).LEfSe revealed the differences in the relative abundance of 6 intestinal bacterial taxa between the WD-3 group and the GC group.At the genus level,Saccharopolyspora had higher relative abundance in the WD-3 group than in the healthy control group and only existed in the WD-3 group.The content of isobutyric acid and isovaleric acid in the WD-3 group was higher than that in the healthy control group(P=0.037,P=0.004).Conclusion WD-3 Mixture may increase the relative abundance of Bifidobacteria and Coprococcus and the content of isobutyric acid and isovaleric acid to alter the intestinal microecology,thereby improving the efficacy of immunotherapy for gastric cancer.


Assuntos
Microbioma Gastrointestinal , Neoplasias Gástricas , Humanos , Isobutiratos , Qualidade de Vida , Neoplasias Gástricas/terapia , Imunoterapia , Resultado do Tratamento
9.
Poult Sci ; 102(9): 102900, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37406441

RESUMO

Excess abdominal fat is a common phenomenon in broiler chickens. Gut microbiota could regulate lipid metabolism through their effects on short-chain fatty acids (SCFAs) production. This study was conducted to investigate the potential relationship between abdominal fat development and cecal microorganism populations. Abdominal fat and cecum contents were collected at 3, 7, 14, 21, 28, 35, and 42 d of age. The results showed that abdominal fat weight increased with age. The abdominal fat percentage was higher between 7 and 21 d of age than at 3 d (P < 0.05), and it increased again at 28 to 42 d (P < 0.05). Morphological analysis showed that adipocyte diameter and cross-sectional area (CSA) increased significantly after 14 d of age (P < 0.05). Moreover, gut microbiota analysis indicated that the Chao1 and Shannon indices were higher between 14 and 28 d than at 3 d of age (P < 0.05). Furthermore, LEfse analysis revealed that Faecalibacterium, Anaerotruncus, Anaeroplasma, Subdoligranulum, and Clostridium emerged to become dominant at 14 d. A greater abundance of Bacteroides, Ruminococcus, Dehalobacterium, and Lactobacillus were determined at 28 d when compared with 14 d of age. Parabacteroides, Ochrobactrum, Lactobacillus, Blautia, Alistipes, Dehalobacterium, Odoribacter, and Suuterella were found to be predominant at 42 d. PICRUSt analysis revealed that amino acid metabolism, lipid metabolism, and terpenoids and polyketides metabolism were elevated at 14 d; the immune and digestive systems were significantly developed at 28 d. In addition, cecum propionic acid and butyric acid contents gradually increased (P < 0.05), while the isobutyric acid contents gradually decreased with advancing age (P < 0.05). Correlation analysis among SCFAs, differential genera and abdominal fat suggested that Coprobacillus, Shigella, and Butyricicoccus had negative correlations with propionic acid, butyric acid, and abdominal fat weight, but positive correlations with isobutyric acid. Isobutyric acid was identified as being negatively associated with abdominal fat weight, while the reverse was found for propionic acid and butyric acid. In conclusion, abdominal fat development is correlated with the emergence of specific microbes and d 14 may be a pivotal age for establishing this relationship.


Assuntos
Microbioma Gastrointestinal , Animais , Propionatos/metabolismo , Galinhas/fisiologia , Isobutiratos/metabolismo , Bacteroidetes , Ácidos Graxos Voláteis/metabolismo , Ceco/microbiologia
10.
Poult Sci ; 102(8): 102789, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37354614

RESUMO

A total of 392 Cobb 500 off-sex male broiler chicks were used in a 21-day experiment to study the effect of protease, xylanase, and xylo-oligosaccharides (XOS) on improving growth performance, nutrient utilization (ileal digestibility and total tract retention), gene expression of nutrient transporters, cecal short-chain fatty acids (SCFAs), and microbiota profile of broilers challenged with Eimeria spp. Chicks at 0-day old were allocated to 8 treatments in a 4 × 2 factorial arrangement: 1) corn-soybean meal diet with no enzyme (Con); 2) Con plus 0.2 g/kg protease alone (PRO); 3) Con plus 0.2 g/kg protease combined with 0.1 g/kg xylanase (PRO + XYL); or 4) Con plus 0.5 g/kg xylo-oligosaccharides (XOS); with or without Eimeria challenge. The 4 diets were formulated to be marginally low in crude protein (183 g/kg). Challenged groups were inoculated with a solution containing E. maxima, E. acervulina, and E. tenella oocysts on d 15. Eimeria depressed (P < 0.01) growth performance and nutrient utilization. Supplemental protease improved (P < 0.05) body weight gain and feed intake in the prechallenge phase (d 0-15) but had no effect during the infection period (d 15-21). There was no interaction between infection and feed supplementation for nutrient utilization. The supplementations of either PRO or XOS alone increased (P < 0.01) total tract retention of Ca and tended (P < 0.1) to improve total tract retention of N, P, AME, and AMEn. Eimeria decreased (P < 0.05) expressions of GLUT2, GLUT5, PepT1, ATP2B1, CaSR, Calbidin D28K, NPT2, and ZnT1 but increased (P < 0.01) expression of GLUT1. XOS supplementation increased (P < 0.05) ATP2B1 expression. Protease decreased (P < 0.05) isobutyrate concentration in unchallenged treatments but not in challenged treatments. Eimeria decreased (P < 0.01) cecal saccharolytic SCFAs acetate and propionate but increased (P < 0.01) branched-chain fatty acid isovalerate. The supplementation of PRO + XYL or XOS increased (P < 0.05) cecal butyrate or decreased cecal isobutyrate concentrations, respectively. PRO + XYL and XOS decreased cecal protein levels in unchallenged birds but not challenged ones. Eimeria challenge significantly (P < 0.05) decreased the microbial richness (Observed features) and diversity (Shannon index and phylogenetic diversity) and changed the microbial composition by reducing the abundance of certain bacteria, such as Ruminococcus torques, and increasing the abundance of others, such as Anaerostipes. In contrast, none of the additives had any significant effect on the cecal microbial composition. In conclusion, PRO or XOS supplementation individually improved nutrient utilization. All the additives decreased the cecal content of branched-chain fatty acids, consistent with decreased cecal N concentration, although the effects were more pronounced in unchallenged birds. In addition, none of the feed additives impacted the Eimeria-induced microbial perturbation.


Assuntos
Coccidiose , Eimeria , Microbiota , Animais , Masculino , Suplementos Nutricionais/análise , Galinhas , Dieta com Restrição de Proteínas/veterinária , Peptídeo Hidrolases/metabolismo , Isobutiratos/metabolismo , Filogenia , Dieta/veterinária , Endopeptidases/metabolismo , Ácidos Graxos Voláteis/metabolismo , Oligossacarídeos/farmacologia , Oligossacarídeos/metabolismo , Nutrientes , Ração Animal/análise , Coccidiose/veterinária , Coccidiose/metabolismo
11.
Int J Mol Sci ; 24(10)2023 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-37240050

RESUMO

Anxiety is one of the most common central nervous system disorders, affecting at least one-quarter of the worldwide population. The medications routinely used for the treatment of anxiety (mainly benzodiazepines) are a cause of addiction and are characterized by many undesirable side effects. Thus, there is an important and urgent need for screening and finding novel drug candidates that can be used in the prevention or treatment of anxiety. Simple coumarins usually do not show side effects, or these effects are much lower than in the case of synthetic drugs acting on the central nervous system (CNS). This study aimed to evaluate the anxiolytic activity of three simple coumarins from Peucedanum luxurians Tamamsch, namely officinalin, stenocarpin isobutyrate, and officinalin isobutyrate, in a 5 dpf larval zebrafish model. Moreover, the influence of the tested coumarins on the expression of genes involved in the neural activity (c-fos, bdnf) or dopaminergic (th1), serotoninergic (htr1Aa, htr1b, htr2b), GABA-ergic (gabarapa, gabarapb), enkephalinergic (penka, penkb), and galaninergic (galn) neurotransmission was assessed by quantitative PCR. All tested coumarins showed significant anxiolytic activity, with officinalin as the most potent compound. The presence of a free hydroxyl group at position C-7 and the lack of methoxy moiety at position C-8 might be key structural features responsible for the observed effects. In addition, officinalin and its isobutyrate upregulated the expression of genes involved in neurotransmission and decreased the expression of genes connected with neural activity. Therefore, the coumarins from P. luxurians might be considered as promising drug candidates for the therapy of anxiety and related disorders.


Assuntos
Ansiolíticos , Animais , Ansiolíticos/farmacologia , Peixe-Zebra/genética , Frutas/química , Isobutiratos/análise , Ansiedade/tratamento farmacológico , Ansiedade/metabolismo , Cumarínicos/química , Expressão Gênica
13.
Nutrients ; 15(7)2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37049552

RESUMO

(1) Background: Non-alcoholic fatty liver disease (NAFLD) is a major global health concern. The increasing prevalence of NAFLD has been related to type 2 diabetes mellitus (T2D). However, the relationship between short-chain fatty acids (SCFAs) and NAFLD severity is ambiguous in T2D subjects. This study aimed to explore the association of SCFAs with the severity of NAFLD in T2D patients. (2) Methods: We employed echography to examine the severity of hepatic steatosis. The serum levels of nine SCFAs, namely, formate, acetate, propionate, butyrate, isobutyrate, methylbutyrate, valerate, isovalerate, and methylvalerate, were measured using gas chromatography mass spectrometry. (3) Results: A total of 259 T2D patients was enrolled in this cross-sectional study. Of these participants, 117 with moderate to severe NAFLD had lower levels of formate, isobutyrate, and methylbutyrate than the 142 without NAFLD or with mild NAFLD. Lower circulating levels of isobutyrate and methylbutyrate were associated with an increased severity of NAFLD. A relationship between NAFLD severity and circulating isobutyrate and methylbutyrate levels was found independently of a glycated hemoglobin (HbA1C) level of 7.0%. (4) Conclusion: Circulating levels of isobutyrate and methylbutyrate were significantly and negatively correlated with NAFLD severity in the enrolled T2D patients. SCFAs may be related to NAFLD severity in T2D patients.


Assuntos
Diabetes Mellitus Tipo 2 , Ácidos Graxos Voláteis , Fígado Gorduroso , Hepatopatia Gordurosa não Alcoólica , Humanos , Ácidos Graxos Voláteis/sangue , Hepatopatia Gordurosa não Alcoólica/sangue , Diabetes Mellitus Tipo 2/sangue , Ultrassonografia , Fígado Gorduroso/diagnóstico por imagem , Isobutiratos/sangue , Estudos Transversais , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais
14.
J Dairy Sci ; 106(5): 3176-3191, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36894426

RESUMO

A multicenter observational study to evaluate genome-wide association was conducted in early-lactation Holstein cows (n = 293) from 36 herds in Canada, the USA, and Australia. Phenotypic observations included rumen metabolome, acidosis risk, ruminal bacterial taxa, and milk composition and yield measures. Diets ranged from pasture supplemented with concentrates to total mixed rations (nonfiber carbohydrates = 17 to 47, and neutral detergent fiber = 27 to 58% of dry matter). Rumen samples were collected <3 h after feeding and analyzed for pH, ammonia, d- and l-lactate, volatile fatty acid (VFA) concentrations, and abundance of bacterial phyla and families. Eigenvectors were produced using cluster and discriminant analyses from a combination of pH and ammonia, d-lactate, and VFA concentrations, and were used to estimate the probability of the risk of ruminal acidosis based on proximity to the centroid of 3 clusters, termed high (24.0% of cows), medium (24.2%), and low risk (51.8%) for acidosis. DNA of sufficient quality was successfully extracted from whole blood (218 cows) or hair (65 cows) collected simultaneously with the rumen samples and sequenced using the Geneseek Genomic Profiler Bovine 150K Illumina SNPchip. Genome-wide association used an additive model and linear regression with principal component analysis (PCA) population stratification and a Bonferroni correction for multiple comparisons. Population structure was visualized using PCA plots. Single genomic markers were associated with milk protein percent and the center logged ratio abundance of the phyla Chloroflexi, SR1, and Spirochaetes, and tended to be associated with milk fat yield, rumen acetate, butyrate, and isovalerate concentrations and with the probability of being in the low-risk acidosis group. More than one genomic marker was associated or tended to be associated with rumen isobutyrate and caproate concentrations, and the center log ratio of the phyla Bacteroidetes and Firmicutes and center log ratio of the families Prevotellaceae, BS11, S24-7, Acidaminococcaceae, Carnobacteriaceae, Lactobacillaceae, Leuconostocaceae, and Streptococcaceae. The provisional NTN4 gene, involved in several functions, had pleiotropy with 10 bacterial families, the phyla Bacteroidetes and Firmicutes, and butyrate. The ATP2CA1 gene, involved in the ATPase secretory pathway for Ca2+ transport, overlapped for the families Prevotellaceae, S24-7, and Streptococcaceae, the phylum Bacteroidetes, and isobutyrate. No genomic markers were associated with milk yield, fat percentage, protein yield, total solids, energy-corrected milk, somatic cell count, rumen pH, ammonia, propionate, valerate, total VFA, and d-, l-, or total lactate concentrations, or probability of being in the high- or medium-risk acidosis groups. Genome-wide associations with the rumen metabolome, microbial taxa, and milk composition were present across a wide geographical and management range of herds, suggesting the existence of markers for the rumen environment but not for acidosis susceptibility. The variation in pathogenesis of ruminal acidosis in the small population of cattle in the high risk for acidosis group and the dynamic nature of the rumen as cows cycle through a bout of acidosis may have precluded the identification of markers for acidosis susceptibility. Despite a limited sample size, this study provides evidence of interactions between the mammalian genome, the rumen metabolome, ruminal bacteria, and milk protein percentage.


Assuntos
Acidose , Doenças dos Bovinos , Feminino , Animais , Bovinos , Rúmen/metabolismo , Amônia/metabolismo , Estudo de Associação Genômica Ampla/veterinária , Isobutiratos , Lactação , Ácidos Graxos Voláteis/metabolismo , Proteínas do Leite/análise , Butiratos/metabolismo , Dieta/veterinária , Bactérias/metabolismo , Lactatos/análise , Acidose/veterinária , Concentração de Íons de Hidrogênio , Fermentação , Mamíferos/metabolismo , Doenças dos Bovinos/metabolismo
15.
J Biol Chem ; 299(4): 103036, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36806679

RESUMO

Staphylococcus aureus controls its membrane biophysical properties using branched-chain fatty acids (BCFAs). The branched-chain acyl-CoA precursors, utilized to initiate fatty acid synthesis, are derived from branched-chain ketoacid dehydrogenase (Bkd), a multiprotein complex that converts α-keto acids to their corresponding acyl-CoAs; however, Bkd KO strains still contain BCFAs. Here, we show that commonly used rich medias contain substantial concentrations of short-chain acids, like 2-methylbutyric and isobutyric acids, that are incorporated into membrane BCFAs. Bkd-deficient strains cannot grow in defined medium unless it is supplemented with either 2-methylbutyric or isobutyric acid. We performed a screen of candidate KO strains and identified the methylbutyryl-CoA synthetase (mbcS gene; SAUSA300_2542) as required for the incorporation of 2-methylbutyric and isobutyric acids into phosphatidylglycerol. Our mass tracing experiments show that isobutyric acid is converted to isobutyryl-CoA that flows into the even-chain acyl-acyl carrier protein intermediates in the type II fatty acid biosynthesis elongation cycle. Furthermore, purified MbcS is an ATP-dependent acyl-CoA synthetase that selectively catalyzes the activation of 2-methylbutyrate and isobutyrate. We found that butyrate and isovalerate are poor MbcS substrates and activity was not detected with acetate or short-chain dicarboxylic acids. Thus, MbcS functions to convert extracellular 2-methylbutyric and isobutyric acids to their respective acyl-CoAs that are used by 3-ketoacyl-ACP synthase III (FabH) to initiate BCFA biosynthesis.


Assuntos
Isobutiratos , Staphylococcus aureus , Staphylococcus aureus/genética , Staphylococcus aureus/metabolismo , Ligases , Ácidos Graxos/metabolismo
16.
Surg Obes Relat Dis ; 19(7): 727-734, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36842931

RESUMO

BACKGROUND: Obesity has reached epidemic dimensions in recent decades. Bariatric surgery (BS) is one of the most effective interventions for weight loss and metabolic improvement in patients with obesity. Short-chain fatty acids (SCFA) are gut microbiota-derived metabolites with a key role in body weight control and insulin sensitivity. Although BS is known to induce significant changes in the gut microbiota composition, its impact on the circulating levels of certain metabolites produced by the gut microbiota such as SCFA remains poorly understood. OBJECTIVE: To determine the impact of BS on the circulating SCFA levels in patients with severe obesity. SETTING: University hospital. METHODS: An observational, prospective study was performed on 51 patients undergoing Roux-en-Y gastric bypass. Plasma samples were collected at baseline (1 day before surgery) and at 6 and 12 months after BS. Plasma SCFA levels were determined by liquid chromatography-mass spectrometry. RESULTS: The results revealed significant changes in the circulating levels of SCFA after BS. A marked increase in propionate, butyrate, isobutyrate, and isovalerate levels and a decrease in acetate, valerate, hexanoate, and heptanoate levels were observed 12 months after BS. Furthermore, the changes in the levels of propionate, butyrate, and isobutyrate negatively correlated with changes in body mass index, while those of isobutyrate correlated negatively with changes in the homeostatic model assessment for insulin resistance index. CONCLUSION: These results suggest that propionate, butyrate, and isobutyrate levels could be related to weight loss and improved insulin sensitivity in patients with severe obesity after BS.


Assuntos
Cirurgia Bariátrica , Resistência à Insulina , Obesidade Mórbida , Humanos , Obesidade Mórbida/cirurgia , Propionatos , Estudos Prospectivos , Isobutiratos , Obesidade/cirurgia , Cirurgia Bariátrica/métodos , Ácidos Graxos Voláteis , Redução de Peso , Butiratos
17.
J Anim Sci ; 1012023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36573478

RESUMO

The objective of this study was to determine the fecal characteristics, microbiota, and metabolites of dogs fed a Saccharomyces cerevisiae fermentation product (SCFP) and subjected to exercise challenge in untrained and trained states. Thirty-six adult dogs (18 male, 18 female; mean age: 7.1 yr; mean body weight: 29.0 kg) were randomly assigned to control or SCFP-supplemented (250 mg/dog/d) diets and fed for 10 wk. After 3 wk, dogs were given an exercise challenge (6.5 km run), with fresh fecal samples collected pre- and post-challenge. Dogs were then trained by a series of distance-defined running exercise regimens over 7 wk (two 6.4 km runs/wk for 2 wk; two 9.7 km runs/wk for 2 wk; two 12.9 km runs/wk for 2 wk; two 3.2 km runs/wk). Dogs were then given exercise challenge (16 km run) in the trained state, with fresh fecal samples collected pre- and post-challenge. Fecal microbiota data were evaluated using QIIME2, while all other data were analyzed using the Mixed Models procedure of SAS. Effects of diet, exercise, and diet*exercise were tested with P < 0.05 considered significant. Exercise challenge reduced fecal pH and ammonia in both treatments, and in untrained and trained dogs. After the exercise challenge in untrained dogs, fecal indole, isobutyrate, and isovalerate were reduced, while acetate and propionate were increased. Following the exercise challenge in trained dogs, fecal scores and butyrate decreased, while isobutyrate and isovalerate increased. SCFP did not affect fecal scores, pH, dry matter, or metabolites, but fecal Clostridium was higher in controls than in SCFP-fed dogs over time. SCFP and exercise challenge had no effect on alpha or beta diversity in untrained dogs. However, the weighted principal coordinate analysis plot revealed clustering of dogs before and after exercise in trained dogs. After exercise challenge, fecal Collinsella, Slackia, Blautia, Ruminococcus, and Catenibacterium were higher and Bacteroides, Parabacteroides, Prevotella, Phascolarctobacterium, Fusobacterium, and Sutterella were lower in both untrained and trained dogs. Using qPCR, SCFP increased fecal Turicibacter, and tended to increase fecal Lactobacillus vs. controls. Exercise challenge increased fecal Turicibacter and Blautia in both untrained and trained dogs. Our findings show that exercise and SCFP may affect the fecal microbiota of dogs. Exercise was the primary cause of the shifts, however, with trained dogs having more profound changes than untrained dogs.


The objective of this study was to determine the fecal characteristics, microbiota, and metabolites of dogs fed a Saccharomyces cerevisiae fermentation product (SCFP) and subjected to exercise challenge in untrained and trained states. Thirty-six adult dogs were randomly assigned to control or SCFP-supplemented (250 mg/d) diets and fed for 10 wk. An exercise challenge was administered while dogs were in an untrained state and a trained state (after 7 wk of an exercise regimen), with fresh fecal samples collected pre- and post-challenge. Exercise challenge reduced fecal pH and ammonia in all dogs. After the exercise challenge in untrained dogs, fecal indole, isobutyrate, and isovalerate concentrations were reduced, while acetate and propionate concentrations were increased. Following exercise challenge in trained dogs, fecal scores and butyrate concentrations decreased, while isobutyrate and isovalerate increased. SCFP reduced fecal Clostridium over time vs. controls. Beta diversity analysis revealed clustering of dogs before and after exercise in trained dogs. After exercise challenge, over 10 bacterial genera were altered in untrained and trained dogs. Our findings show that exercise and SCFP may affect the fecal microbiota of dogs, but exercise was the primary cause of the shifts and trained dogs had more profound changes than untrained dogs.


Assuntos
Microbiota , Saccharomyces cerevisiae , Cães , Feminino , Masculino , Animais , Saccharomyces cerevisiae/metabolismo , Fermentação , Isobutiratos/metabolismo , Ração Animal/análise , Dieta/veterinária , Fezes
18.
Front Endocrinol (Lausanne) ; 13: 1013959, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36204098

RESUMO

Background: Single-anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) is one of the most effective bariatric procedures in the treatment of type 2 diabetes mellitus (T2DM). However, the mechanisms by which SADI-S improves T2DM are not well-known. Objective: To explore the effects of SADI-S on metabolites in the stool of rats with T2DM. Methods: Twenty rats were fed on high-fat diet and administered with a low-dose (30mg/kg) of streptozotocin to establish T2DM models. The rats were then randomly assigned to the SADI-S group (n=10) and sham operation group (n=9). Stool samples were collected from all rats at 8 weeks after surgery and stored at -80 °C. Metabolomics analysis was performed to identify differential metabolites through ultra- performance liquid chromatography-mass spectrometry. Results: At 8-week after surgery, rats of the SADI-S group showed significantly decreased fasting blood glucose, glucose tolerance test 2-hour, glycated haemoglobin, and body weight compared with those of the sham group. A total of 245 differential metabolites were identified between the two groups. Among them, 16 metabolites such as branched-chain amino acids (valine), aromatic amino acid (phenylalanine), bile acid (cholic acid, lithocholic acid, and ß-muricholic acid), short-chain fatty acid (isobutyric acid), and phospholipid [lysoPE(17:0), lysoPE(20:3) and lysoPS(16:0)] were associated to the T2DM remission after SADI-S. Conclusion: SADI-S improves T2DM in rats by regulating phenylalanine biosynthesis, valine, phenylalanine, alanine, glutamate, proline, bile acid, and phospholipid metabolism pathways.


Assuntos
Diabetes Mellitus Tipo 2 , Obesidade Mórbida , Animais , Ratos , Alanina , Aminoácidos Aromáticos , Aminoácidos de Cadeia Ramificada , Anastomose Cirúrgica/métodos , Ácidos e Sais Biliares , Glicemia/análise , Diabetes Mellitus Tipo 2/cirurgia , Gastrectomia/métodos , Glutamatos , Hemoglobinas Glicadas/análise , Íleo/química , Íleo/cirurgia , Isobutiratos , Ácido Litocólico , Obesidade Mórbida/cirurgia , Fenilalanina , Fosfolipídeos , Prolina , Estreptozocina , Valina
19.
Nutrients ; 14(19)2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36235606

RESUMO

BACKGROUND: Short-chain fatty acids (SCFA) play a key role in the gut microbiota-brain crosstalk regulating the main neurodevelopmental processes during pregnancy. The aim of this study is to investigate the longitudinal relationship between prenatal levels of the main SCFAs in maternal serum and infant cognitive development and temperament on day 40 postpartum after adjusting for several pre-, peri- and post-natal confounders. METHODS: A sample of 357 healthy mother-infant pairs were followed from the beginning of pregnancy to 40 days after birth. Serum SCFA concentrations were assessed in the first and third trimester of pregnancy by LC-MS/MS; and socio-demographic, nutritional, and psychological variables were collected. At 40 days, the Bayley Scales of Infant Development-III and the Early Infancy Temperament Questionnaire were administered. RESULTS: Lower serum levels of acetic, butyric and isobutyric acid, mainly during the first trimester, were related to better language and psychomotor development and, in the case of butyric acid, better intensity behavior in infants. Medium levels of propionic acid were related to better scores for development, mood and temperament. CONCLUSIONS: These findings suggest that in a community sample of healthy pregnant women from a Mediterranean region of northern Spain, lower serum levels of SCFAs, especially in the first trimester of pregnancy, seem to be related to better infant neurodevelopment.


Assuntos
Isobutiratos , Propionatos , Criança , Cromatografia Líquida , Ácidos Graxos Voláteis , Feminino , Humanos , Lactente , Parto , Gravidez , Espectrometria de Massas em Tandem
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