BIOPHARMACEUTICS & DRUG DISPOSITION
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2022
·Vol. 43
·期 6
·247-254
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IF 1.831
Ting Zhu,Yu Wu,Xue-Mei Li,Yu-Meng Jia,Huan Zhou,Li-Ping Jiang,Ting Tai,Qiong-Yu Mi,Jin-Zi Ji,Hong-Guang Xie
As an analog of clopidogrel and prasugrel, vicagrel is completely hydrolyzed to intermediate thiolactone metabolite 2-oxo-clopidogrel (also the precursor of active thiol metabolite H4) in human intestine, predominantly by AADAC and CES2; however, other unknown vicagrel hydrolases remain to be identified. In this study, recombinant human Raf kinase inhibitor protein (rhRKIP) and pooled human intestinal S9 (HIS9) fractions and microsome (HIM) preparations were used as the different enzyme sources; prasugrel as a probe drug for RKIP (a positive control), vicagrel as a substrate drug of interest, and the rate of the formation of thiolactone metabolites 2-oxo-clopidogrel and R95913 as metrics of hydrolase activity examined, respectively. In addition, an IC 50 value of inhibition of rhRKIP-catalyzed vicagrel hydrolysis by locostatin was measured, and five classical esterase inhibitors with distinct esterase selectivity were used to dissect the involvement of multiple hydrolases in vicagrel hydrolysis. The results showed that rhRKIP hydrolyzed vicagrel in vitro, with the values of K m , V max , and CL int measured as 20.04 ± 1.99 μM, 434.60 ± 12.46 nM/min/mg protein, and 21.69 ± 0.28 ml/min/mg protein, respectively, and that an IC 50 value of locostatin was estimated as 1.24 ± 0.04 mM for rhRKIP. In addition to locostatin, eserine and vinblastine strongly suppressed vicagrel hydrolysis in HIM. It is concluded that RKIP can catalyze the hydrolysis of vicagrel in the human intestine, and that vicagrel can be hydrolyzed by multiple hydrolases, such as RKIP, AADAC, and CES2, concomitantly.
研究领域:
药理学
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生物化学
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DOI
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2022
·
IF 7.425
Xueting Guan,Yujing Feng,Yunyao Jiang,Yeye Hu,Ji Zhang,Zhengpeng Li,Chao Song,Fu Li,Jincai Hou,Ting Shen,Weicheng Hu
Lotus root polysaccharide (LRP) is an active water-soluble polysaccharide with average molecular weight of 1.24 × 10 4 . It was composed of (1 → 4)-α-D-glucan backbone with α-D-glycopyranosyl moieties connected to C-6 positions of the glucose residues as side chains approximately every six residues. However, little information is available for its digestion and fermentation characteristics in vitro . The results showed that the levels of reducing sugars were increased slightly, and the molecular weight was also reduced slightly, in simulated gastric and small intestinal juices. During in vitro fermentation, the total sugar, reducing sugar and glucose contents decreased gradually with increasing fermentation time. The molecular of LRP was degraded and to metabolize into a variety the short-chain fatty acids (SCFAs) such as acetic, propionic, and butyric acids. Furthermore, LRP fermentation decreased the pH of the fermentation broth and increased its absorbance. Meanwhile, LRP modulated the gut microbiota by altering the Firmicutes / Bacteroidetes ratio and increasing the relative abundance of Bifidobacterium . The findings from this study showed that LRP could be developed as potential prebiotic to regulate the composition of gut microbiota, thereby promote the production of SCFAs.
研究领域:
食品科学
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微生物学
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营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2024
·
IF 5.1
Dan Yuan,Wenqian Xiao,Ao Gao,Wei Lu,Zhiming Gao,Bing Hu,Yuehan Wu,Wenxin Jiang,Yanlei Li
The degradation of sodium alginate by human gut microbiota was found to be retarded via calcium cross-linking in our previous study. We hypothesized that the guluronic acid block (GB) on the alginate molecule might be the key structural region affecting alginate degradation by the gut microbiota when cross-linked with calcium. This study aims to prove this hypothesis by studying the structural features of the cross-linked GB on its in vitro fecal fermentation behaviors concerning the aspects of total carbohydrate contents, monosaccharide contents, short-chain fatty acids production, calcium state variations, and structural variations. Herein, GB isolated from sodium alginate was cross-linked under ranges of molar ratios of [Ca2+]/[–COOH] that further restricted the degradation by gut microbiota similar to the cross-linked alginates. First, total carbohydrate contents, short-chain fatty acids production, monosaccharides contents, and calcium state analyses confirmed that the degradation of GB by gut microbiota was restricted by calcium cross-linking. Furthermore, the tracking analysis of structural variations during in vitro fermentation revealed that the “granules” structure could further restrict degradation by the gut microbiota, leaving more cross-linked GB fragments surviving in comparison to the “networks” structure. In addition, Bacteroides xylanisolvens showed a significant positive correlation to the “cross-linking porosity (R = 0.825, p < 0.001), which supported our previous findings on fermentation behaviors of cross-linked alginate. Together, guluronic acid blocks are the key structural regions that retard the degradation of sodium alginate by the gut microbiota when cross-linked with calcium.
研究领域:
食品科学
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微生物学
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营养学
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2024
·
IF 10.7
Fang Ting Gu,Jun Hui Li,Zi Chen Zhao,Yan Yu Zhu,Lin Xi Huang,Jian Yong Wu
This study was to assess the digestion and colonic fermentation of two bioactive polysaccharides, EPS-LM and LBPS, and the subsequent influences on human gut microbiota through simulated gastrointestinal systems. EPS-LM, an exopolysaccharide isolated from mycelial culture of a medicinal fungus Cordyceps sinensis Cs-HK1, was characterized as a heteropolysaccharide consisting of Man(108):Gal(52.7):Glc(29.2) (molar ratio) with an average molecular weight (MW) 5.513 × 10 6 . LBPS was isolated from a well-known medicinal plant ( Lycium barbarum L.) which was also characterized as a heteropolysaccharide (1.236 × 10 5 MW). Both polysaccharides were highly resistant to saliva, gastric and small-intestine digestion with negligible MW reduction and release of reducing sugars but were quickly degraded to lower MW during in vitro human fecal fermentation. They were consumed as a carbon source by the gut bacteria to produce short-chain fatty acids (SCFAs). In comparison, the carbohydrate content of EPS-LM was more completely consumed than LBPS and there were also notable differences in consumption of specific monosaccharides and production of specific SCFAs, propionic and butyric acid, and relative abundance of gut bacterial populations between EPS-LM and LBPS group. The results suggest that metabolic outcomes and modulating effects of EPS-LM and LBPS on the gut microbiota are highly dependent on their molecular composition.
研究领域:
微生物学
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营养科学
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胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2020
·
IF 3.701
Vemana Gowd,Lianghua Xie,Chongde Sun,Wei Chen
Bayberry (BB) fruits contain high levels of polyphenols and possess good bioactivities. However, there are no specific studies to illustrate the impact of human gut microbiota fermentation (HGMF) on BB polyphenols subjected to gastrointestinal digestion (GID). Therefore, in this study, BB was subjected to simulated GID and HGMF (0–48 h) in order to study the fate of BB bioactive components. Phenolic gut metabolites were identified and quantified by relevant standards using HPLC. Cyanidin-3- O -glucoside was the only anthocyanin in BB and could be detected in its free form even after gut fermentation for 24 h. Gut metabolites of BB showed better hypoglycemic activity by improving hepatic glucose consumption and glycogen content. Furthermore, gut metabolites significantly ameliorated glucolipotoxicity induced oxidative stress. Since BB gut metabolites showed good hypoglycemic and antioxidant activities, BB can be considered as a functional food and dietary supplementation of BB could help in maintenance of good health.
研究领域:
食品科学
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营养学
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药理学
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微生物学
✓ 已验证
产品关联
DOI
高影响因子
CHEMOSPHERE
·
2021
·
IF 7.086
Shuqing Zhou,Min Jin,Rong Tan,Zhiqiang Shen,Jing Yin,Zhigang Qiu,Zhengshan Chen,Danyang Shi,Haibei Li,Zhongwei Yang,Huaran Wang,Zhixian Gao,Junwen Li,Dong Yang
The latent dangers of waterborne viral transmission have become a major public health concern. In this study, reduced graphene oxide (rGO)-Fe 3 O 4 nanoparticles were decorated with cetyltrimethylammonium bromide (CTAB) to adsorb severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike pseudovirus and three human enteric viruses (HuNoV, HRV, and HAdV). The successful combination of CTAB with rGO-Fe 3 O 4 was confirmed by transmission electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, zeta potential, Brunner-Emmet-Teller, and vibrating sample magnetometer measurements. The adsorption of HuNoV and HAdV followed pseudo-first-order kinetics, while that of HRV conformed to the pseudo-second-order model. CTAB-functionalized rGO-Fe 3 O 4 exhibited exceptionally high adsorption of HuNoV, HRV, HAdV and SARS-CoV-2 spike pseudovirus, with maximum adsorption capacities of 3.55 × 10 7 , 7.01 × 10 7 , 2.21 × 10 7 and 6.92 × 10 6 genome copies mg −1 , respectively. Moreover, the composite could effectively adsorb the four types of virus particles from coastal, tap, and river water. In addition, concentrating the virions using CTAB functionalized rGO-Fe 3 O 4 composites before qPCR analysis significantly improved the detection limit. The results indicate that viruses are captured on the surface of CTAB functionalized rGO-Fe 3 O 4 composites through electrostatic interactions and the intrinsic adsorption ability of rGO. Overall, CTAB-functionalized rGO-Fe 3 O 4 composites are promising materials for the adsorption and detection of human enteric viruses as well as SARS-CoV-2 from complex aqueous environments.
研究领域:
环境科学
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生物学
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材料科学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Guoqiang Zhang,Jieke Du,Chengsong Zhang,Zhiyi Zhao,Yuexing Chen,Mingyu Liu,Jianwei Chen,Guangyi Fan,Li Ma,Shengying Li,Kun Liu
Widespread use of polyethylene terephthalate (PET) plastics and their recycling challenges have led to substantial accumulation of PET wastes in global environments, with inevitable consequences for their entry into the food chains. Recent studies have increasingly documented the ingestion of microplastics by humans through food and beverages. However, the fate of these microplastics within the gastrointestinal tract, particularly the role of the human gut microbiota, remains inadequately understood. To address this knowledge gap, we employed a bioinformatics workflow integrated with functional verification to investigate the PET digestion/degradation capabilities of intestinal microorganisms. This approach identified a novel PET hydrolase—HGMP01 from the human gut metagenome, which exhibits the capacity to hydrolyze PET nanoparticles. Moreover, comprehensive exploration for HGMP01 homologues in the human gut metagenome and metatranscriptome unveil their distribution in diverse intestinal microorganisms. This study provides biochemical evidence for an unforeseen role of human gut microbiome in plastic digestion, thus holding substantial implications for human health.
研究领域:
环境科学
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微生物学
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生物化学
·
人类健康
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2018
·
IF 3.412
Wangting Zhou,Yamei Yan,Jia Mi,Hongcheng Zhang,Lu Lu,Qing Luo,Xiaoying Li,Xiaoxiong Zeng,Youlong Cao
Digestion and fermentation in vitro of polysaccharides from bee collected pollen of Chinese wolfberry (WBPPS) were investigated in the present study. It was found that WBPPS mainly consisted of mannose, ribose, rhamnose, galacturonic acid, glucose, galactose, xylose, and arabinose in a molar ratio of 0.38:0.09:0.17:0.64:0.22:0.67:0.08:1.03, respectively. WBPPS was not affected by human saliva. The fraction A (molecular weight 1340 kDa) of WBPPS was not broken down in simulated gastric and small intestinal juices, while the small fraction B (molecular weight 523 kDa) of WBPPS was degraded. Moreover, fermentation in vitro revealed that WBPPS could significantly enhance the production of short-chain fatty acids and modulate gut microbiota composition via increasing the relative abundances of genera Prevotella, Dialister, Megamonas, Faecalibacterium, and Alloprevotella and decreasing the numbers of genera Bacteroides, Clostridium XlVa, Parabacteroides, Escherichia/Shigella, Phascolarctobacterium, Parasutterella, Clostridium sensu stricto, and Fusobacterium.
研究领域:
食品科学
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微生物学
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营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2020
·
IF 4.236
Chen Miao,Liu Shujun,Imam Khandaker Md. Sharif Uddin,Sun Lichao,Wang Yulu,Gu Tianyi,Wen Boting,Xin Fengjiao
Wheat bran is a cereal rich in dietary fibers that have high levels of ferulic acid, which has prebiotic effects on the intestinal microbiota and the host. Herein we explored the effect of xylooligosaccharide, xylan, and whole wheat bran on the human gut bacteria and screened for potential ferulic acid esterase genes. Using in vitro fermentation, we analyzed the air pressure, pH-value, and short-chain fatty acid levels. We also performed 16S rRNA gene and metagenomic sequencing. A Venn diagram analysis revealed that 80% of the core operational taxonomic units (OTUs) were shared among the samples, and most of the xylooligosaccharide treatment core OTUs (319/333 OTUs) were shared with the other two treatments’ core OTUs. A significant difference analysis revealed that the relative abundance of Dorea, Bilophila, and Sulfurovum in wheat bran treatment was higher than that in xylan and xylooligosaccharide treatments. The clusters of orthologous groups of proteins functional composition of all samples was similar to the microbiota composition of the control. Using metagenomic sequencing, we revealed seven genes containing the conserved residues, Gly-X-Ser-X-Gly, and the catalytic triad, Ser-His-Asp, which are thus potential ferulic acid esterase genes. All the results indicate that xylan and/or xylooligosaccharide, the main dietary fibers in wheat bran, plays a major role in in vitro fermentation by the human gut microbiota.
研究领域:
微生物学
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营养科学
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胃肠病学
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基因组学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2021
·
IF 6.953
Juanjuan Tian,Xiaomeng Wang,Xueliang Zhang,Xiaohong Chen,Xin Rui,Qiuqin Zhang,Mingsheng Dong,Wei Li
This study aimed to explore the in vitro simulated digestion and fecal fermentation behaviors of two purified exopolysaccharide fractions (EPS1 and EPS2) from Paecilomyces cicadae TJJ1213 and its effects on human gut microbiota composition. Results showed that EPS1 and EPS2 could not be digested by saliva-gastrointestinal. After fecal fermentation, however, the molecular weight of EPS1 and EPS2 significantly decreased, and the molar ratios of the monosaccharide composition remarkably changed, indicating that EPS1 and EPS2 could be degraded and consumed by human gut microbiota. Notably, EPS1 and EPS2 could significantly modulate the composition, via increasing the relative abundances of Bacteroides and Phascolarctobacterium and decreasing the pathogenic bacteria Escherichia-Shigella, Klebsiella and Fusobacterium . In addition, EPS1 and EPS2 also could promote the production of short-chain fatty acids during fermentation for 24 h. These results suggested that EPS from Paecilomyces cicadae TJJ1213 can be used as a functional food to improve health and prevent diseases by promoting gut health.
研究领域:
微生物学
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营养科学
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胃肠病学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2025
·
IF 3.1
Hangming Li,Lue Hong,Yijun Wang,Shuo Chai,Ping Huang,Hongmei Chen,Wenhong Liu,Wei Zhu,Massimo Marzorati,Hui Wang,Jingkui Tian,Xiaoyong Zhang
Atractylodes macrocephalae Rhizoma (AMR), a traditional Chinese medicine, is extensively utilized in clinical practice for its pharmacological properties, including anti-inflammatory, anti-tumor, and gastrointestinal regulatory effects. Nonetheless, the intricate nature of traditional Chinese medicine extracts has resulted in few studies into the effects of compositional variations in Atractylodes macrocephalae Rhizoma extracts (AMRE) from diverse sources on gastrointestinal metabolic processes. This study developed an integrated in vitro and in vivo compound analysis strategy utilizing Ultrahigh-performance liquid chromatography Quadrupole-Orbitrap tandem mass spectrometry (UHPLC-Q-Orbitrap-MS/MS) and the Simulator of Human Intestinal Microbial Ecosystem (SHIME) to examine the metabolic alterations caused by variations in the chemical constituents of AMRE from diverse sources. A total of 117 chemical constituents were found, primarily classified as terpenoids, organic acids, alkaloids, coumarins, and phenylpropanoids. 51 prototype components and 79 metabolites were identified. The metabolic processes were predominantly observed among terpenoids, with reaction types encompassing hydroxylation, oxidation, hydrogenation, methylation, glucuronidation, and sulfonation. Analysis of dynamic changes revealed that the majority of the prototype components underwent a considerable reduction in the colon, while the metabolites were markedly enriched in both the small intestine and colon. Differential analysis showed that AMRE3 contained the highest number of terpenoid compounds, AMRE1 exhibited the highest average content of chemical constituents, and AMRE2 had the lowest. These disparities were consistently observed in both prototype components and metabolic behaviors, thereby affirming the robust correlation between metabolite distribution and chemical constituents. This study elucidates, for the first time, the variations in the chemical constituents of AMRE from diverse sources and the metabolic characteristics and discrepancies they elicit in the human gastrointestinal tract (GI tract), offering a viable strategy for further clarifying the material basis of its pharmacological effects and clinical applications.
研究领域:
药理学
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中医药学
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分析化学
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代谢组学
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胃肠病学
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微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Host & Microbe
·
2025
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IF 18.7
Hongbin Liu,Juntao Shen,Zhiwei Zhang,Jiuming Wang,Chengxin Zhang,Linggang Zheng,Haoran Ni,Liang Hong,Jieqiong Zhang,Dongfang Xue,Jiayang Chen,Qinze Yu,Zepeng Qu,Yingfei Ma,Tong Si,Liangzhen Zheng,Sheng Wang,Changtao Jiang,Yu Li,Kai Wang,Lei Dai
The human gut microbiome contains numerous proteins whose functions remain elusive yet are pivotal to host health. Sequence-based methods often falter when attempting to infer functions within this microbial proteome due to evolutionary divergence. To address this challenge, we develop the Human Gut Microbial Protein Structure Database, which incorporates ∼2.7 million predicted protein structures. Our findings reveal that structural analogy enhances the annotation of phage proteins. We detail the structural diversification of phage endolysins and confirm their potential in eliminating gut pathobionts. Furthermore, our structure-guided approach is effective in the identification of microbial-host isozymes. By employing structural alignments, we identify previously unrecognized bacterial enzymes involved in melatonin biosynthesis. Finally, we present an alignment-free method, dense enzyme retrieval, based on structure-encoded protein language models for ultrafast and sensitive detection of remote homologs. Our research underscores the value of computational structural genomics in elucidating the functional landscape of the human gut microbiome.
研究领域:
微生物组研究
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结构生物信息学
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计算生物学
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宏基因组学
·
酶发现
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）