ANALYTICA CHIMICA ACTA
·
2022
·
IF 6.911
Yan-Zhen Wang,Peng-Cheng Mei,Pei-Rong Bai,Na An,Jin-Gang He,Jie Wang,Quan-Fei Zhu,Yu-Qi Feng
Bile acids (BAs) are a class of vital gut microbiota-host cometabolites, and they play an important role in maintaining gut microbiota-host metabolic homeostasis . Very recently, a new mechanism of BA anabolic metabolism mediated by gut microbiota (BA-amino acid conjugation) has been revealed, which provides a perspective for the research on BA metabolism and gut metabolome . In this study, we established a polarity-switching multiple reaction monitoring mass spectrometry-based screening method to mine amino acid-conjugated bile acids (AA-BAs) derived from host-gut microbiota co-metabolism. In addition, a retention time-based annotation strategy was further proposed to identify the AA-BA isomers and epimers . Using the developed methods, we successfully screened 118 AA-BA conjugates from mouse and human feces, 28 of them were confirmed by standards, and 62 putatively identified based on their predicted retention times. Moreover, we observed that the levels of most AA-BAs were significantly downregulated in the feces of chronic sleep deprivation mice, suggesting that the AA-BA metabolism was closely related to the physiological state of the host.
研究领域:
生物化学
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代谢组学
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微生物学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2017
·
IF 5.099
Qian Liu,Wentao Shao,Chunlan Zhang,Cheng Xu,Qihan Wang,Hui Liu,Haidong Sun,Zhaoyan Jiang,Aihua Gu
Organochlorine pesticides (OCPs) can persistently accumulate in body and threaten human health. Bile acids and intestinal microbial metabolism have emerged as important signaling molecules in the host. However, knowledge on which intestinal microbiota and bile acids are modified by OCPs remains unclear. In this study, adult male C57BL/6 mice were exposed to p, p’-dichlorodiphenyldichloroethylene (p, p’-DDE) and β-hexachlorocyclohexane (β-HCH) for 8 weeks. The relative abundance and composition of various bacterial species were analyzed by 16S rRNA gene sequencing. Bile acid composition was analyzed by metabolomic analysis using UPLC-MS. The expression of genes involved in hepatic and enteric bile acids metabolism was measured by real-time PCR. Expression of genes in bile acids synthesis and transportation were measured in HepG2 cells incubated with p, p’-DDE and β-HCH. Our findings showed OCPs changed relative abundance and composition of intestinal microbiota, especially in enhanced Lactobacillus with bile salt hydrolase (BSH) activity. OCPs affected bile acid composition, enhanced hydrophobicity , decreased expression of genes on bile acid reabsorption in the terminal ileum and compensatory increased expression of genes on synthesis of bile acids in the liver. We demonstrated that chronic exposure of OCPs could impair intestinal microbiota; as a result, hepatic and enteric bile acid profiles and metabolism were influenced. The findings in this study draw our attention to the hazards of chronic OCPs exposure in modulating bile acid metabolism that might cause metabolic disorders and their potential to cause related diseases in human.
研究领域:
毒理学
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微生物学
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代谢组学
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环境健康
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DOI
PubMed
高影响因子
INTERNATIONAL DAIRY JOURNAL
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2013
·
IF 2.333
C.F. Guo,J.Y. Li
Elevated serum cholesterol is a major risk factor for coronary artery disease. Probiotics may manage elevated cholesterol. The hypocholesterolaemic effects of Lactobacillus casei F0822 and its functional mechanisms were investigated in rats . The serum total cholesterol, low-density lipoprotein cholesterol and liver total cholesterol levels significantly decreased in rats fed a high-cholesterol diet plus drinking water supplemented with viable cells of strain F0822; however, there was no significant difference in the serum high-density lipoprotein cholesterol levels among the treatment groups. The hypocholesterolaemic mechanisms of strain F0822 were attributed to its ability to suppress the reabsorption of bile acids into the enterohepatic circulation though hydrolysis of conjugated bile acids in the small intestine, binding of deoxycholic acid and hyodeoxycholic acid in the large intestine, and increase in propionate:acetate ratio in the large intestine in rats. Strain F0822 may be a promising probiotic culture with potential hypocholesterolaemic action in human.
研究领域:
营养学
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医学
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微生物学
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产品关联
DOI
高影响因子
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
·
2022
·
IF 5.011
Zhicheng Duan,Tingting Yang,Lin Li,Xue Wang,Chujing Wei,Ziyin Xia,Yuanyuan Chai,Xin Huang,Luyong Zhang,Zhenzhou Jiang
Bile acids (BAs) were selected as biomarkers for the diagnosis and prevention of multiple liver diseases, and they were also considered as an important signal transductor via “liver-gut” axis. As important factors for maintaining the normal function and tissue morphology, BA homeostasis throughout the enterohepatic circulation system was guaranteed by BA synthases and transporters, nuclear receptors (NRs) and gut microbiota , all of which presented significant species differences. Thus, we simultaneously quantify BA profiles in the enterohepatic circulation of SD rats and C57BL/6 mice to reveal the species differences of BA homeostasis between these two main rodents of preclinical studies . Our results showed that BA profiles of mice plasma, bile and liver were most dissimilar from these of rats. Meanwhile, BAs profiles also presented obvious species differences in the intestine of mice and rats, especially small intestine . Unlike rats, taurine-conjugated bile acids (T-BAs) were predominant in mice small intestine content and tissue, in which taurocholic acid (TCA) was the most prominent BAs. BAs dynamic analysis showed that compared with rats, mice showed stranger taurine and glycine de-conjugations in lager intestine. However, both the ratios of unconjugated bile acids (Un-BAs) to conjugated BAs, and secondary BAs to primary BAs in mice small content and tissue were all much lower than these in rats. Furthermore, ileum BAs profiles also showed significantly separation trend between rats and mice, whether content or tissue. Our data revealed that the patterns of BAs homeostasis in mice enterohepatic circulation system were significantly different from these in rats (especially in intestine), suggesting that more cautious should be paid to the selection of BAs as biomarkers for disease diagnosis or/and drug induced toxicity, and the certain role and mechanism of individual BA in the pathological process of BA-related diseases via “liver-gut” axis should be verified by using of multiple species.
研究领域:
生物学
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医学
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产品关联
DOI
PubMed
高影响因子
CELL
·
2024
·
IF 45.5
Qixing Nie,Xi Luo,Kai Wang,Yong Ding,Shumi Jia,Qixiang Zhao,Meng Li,Jinxin Zhang,Yingying Zhuo,Jun Lin,Chenghao Guo,Zhiwei Zhang,Huiying Liu,Guangyi Zeng,Jie You,Lulu Sun,Hua Lu,Ming Ma,Yanxing Jia,Ming-Hua Zheng,Yanli Pang,Jie Qiao,Changtao Jiang
The gut microbiota has been found to play an important role in the progression of metabolic dysfunction-associated steatohepatitis (MASH), but the mechanisms have not been established. Here, by developing a click-chemistry-based enrichment strategy, we identified several microbial-derived bile acids, including the previously uncharacterized 3-succinylated cholic acid (3-sucCA), which is negatively correlated with liver damage in patients with liver-tissue-biopsy-proven metabolic dysfunction-associated fatty liver disease (MAFLD). By screening human bacterial isolates, we identified Bacteroides uniformis strains as effective producers of 3-sucCA both in vitro and in vivo . By activity-based protein purification and identification, we identified an enzyme annotated as β-lactamase in B. uniformis responsible for 3-sucCA biosynthesis. Furthermore, we found that 3-sucCA is a lumen-restricted metabolite and alleviates MASH by promoting the growth of Akkermansia muciniphila . Together, our data offer new insights into the gut microbiota-liver axis that may be leveraged to augment the management of MASH.
研究领域:
医学
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微生物学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Jie Li,Xiaolong Lian,Baojian Li,Quhuan Ma,Lingling Yang,Guangmiao Gao,Tingmei Yin,Xiaoyan Fu,Yi Deng,Zhijun Yang,Xiujuan Yang
Ethnopharmacological relevance Cisplatin (CP), a widely used antineoplastic agent, is a leading cause of drug-induced liver injury (DILI) due to its hepatotoxic effects. Licorice (GC), an established remedy in traditional Chinese medicine (TCM), has shown promise in addressing liver diseases and DILI. Nonetheless, the specific active components and underlying mechanisms of GC in mitigating CP-induced liver injury remain inadequately investigated. Aim of the study This study examined the active components and efficacy of GC in addressing CP-induced hepatotoxicity, focusing on its mechanisms related to bile acid metabolism and gut microbiota regulation. Materials and methods Utilizing a CP-induced rat liver injury model, this study evaluated changes in liver coefficient, liver function indices, and pathological morphology while assessing the efficacy of GC for both prevention and treatment of CP-induced liver injury. Subsequently, UPLC-Q-TOF-MS qualitatively analyzed GC's blood-entering components, elucidating its pharmacodynamic material basis. Network pharmacology analysis identified potential pathways and targets of GC's blood components in relation to CP-induced liver injury. Furthermore, metabolomics and 16S rRNA sequencing were employed to clarify the pharmacodynamic mechanisms of GC in modulating bile acid metabolism and gut microbiota, offering insights into its preventive and therapeutic roles. Results The pharmacodynamic results revealed that GC significantly reduced liver function biomarkers and improved pathological changes in liver tissue. UPLC-Q-TOF-MS analysis identified 16 blood-entering components as potential pharmacodynamic agents of GC for preventing and treating CP-induced liver injury. Network pharmacology analysis suggested a link between GC's efficacy and the bile acid metabolic pathway. Furthermore, metabolomics analysis, immunoblotting, and 16S rRNA sequencing demonstrated that GC regulated bile acid metabolites in both liver and feces, enhanced FXR and BSEP expressions in the liver, and decreased CYP27A1 expression. Additionally, GC mitigated CP-induced intestinal dysbiosis by altering the abundance of gut microbiota. Conclusions UPLC-Q-TOF-MS performed a qualitative analysis of 16 blood-entering components linked to GC, providing a basis for further exploration of the pharmacodynamic material underpinning GC. The protective role of GC in CP-induced liver injury appears connected to enhanced bile acid metabolism and restoration of gut microbiota balance.
研究领域:
民族药理学
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药理学
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代谢组学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Biotechnology Journal
·
2024
·Vol. 19
·期 11
·e202400518
·
IF 3.2
Fangzhi Deng,Zhenru Zhou,Zhen Du,Mohamed Mohany,Qunyue Wu,Weiyang Liang,Lei Zhang,Shan Li
Murideoxycholic acid (MDCA), as a significant secondary bile acid derived from the metabolism of α/β-muricholic acid in rodents, is an important component in maintaining the bile acid homeostasis. However, the biosynthesis of MDCA remains a challenging task. Here, we present the development of cytochrome P450 monooxygenase CYP102A1 (P450 BM3) from Bacillus megaterium , employing semi-rational protein engineering technique. Following three rounds of mutagenesis, a triple variant (T260G/G328A/L82V) has been discovered that proficiently catalyzes the 6β-hydroxylation of lithocholic acid (LCA), thereby generating MDCA with an impressive 8.5-fold increase in yield compared to the template P450 BM3 mutant. The MDCA selectivity has been also promoted from 62.0% to 96.3%. This biocatalyst introduces a novel approach for the biosynthesis of MDCA from LCA. Furthermore, molecular docking and dynamics simulations have been employed to unravel the molecular mechanisms underlying the enhanced LCA conversion and MDCA selectivity.
研究领域:
生物化学
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分子生物学
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DOI
PubMed
高影响因子
Food & Function
·
2025
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IF 5.4
Yan Liu,Tian Zhao,Zhangtie Wang,Yansong Zhang,Jianfu Shen,Baiyi Lu
Cholesterol is an important lipid molecule that can affect the gut microbiome upon ingestion. We systematically investigated the effects of cholesterol on the microbiota of the large and small intestines using ex vivo and in vivo models, combining flow cytometry, metabolomics, and metagenomics. The results showed that cholesterol directly causes a loss of bacterial membrane polarity and integrity, as well as a reduction in microbial metabolic activity. Cholesterol directly affected the global metabolism of the large and small intestine microbiota, including amino acid, carbohydrate, and nucleotide metabolism. Ex vivo and in vivo studies shared similar results, showing that cholesterol increased the abundance of the primary bile acid-metabolizing bacteria Clostridium and Dorea in the large intestinal microbiota, confirming the enrichment effect of cholesterol on these bacteria. In the in vivo model, increased conjugated bile acids in the small intestine and decreased abundance of BSH-containing Bifidobacterium were observed due to cholesterol. Only in vivo models have demonstrated that cholesterol increases phosphatidylcholine levels in both the small and large intestine, which may be related to the effects of cholesterol on host metabolism. The pro-inflammatory capacity of the intestinal microbiota was enhanced by cholesterol, as evidenced by the increased levels of IL-1β and TNF-α in THP-1 cells upon stimulation with cholesterol-treated microbiota. This study comprehensively elucidates the effects of cholesterol on the composition and metabolic functions of the microbiota in both the large and small intestines. It offers a novel perspective on the ways in which cholesterol affects host metabolism via the gut microbiome.
研究领域:
营养学
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微生物学
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代谢生物学
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DOI
PubMed
高影响因子
Aquaculture Reports
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2022
·
IF 3.385
Jia Xu,Chaozhong Zheng,Shuyan Chi,Shuang Zhang,Junming Cao,Beiping Tan,Shiwei Xie
Dietary Clostridium autoethanogenum protein (CAP) has the potential to replace fishmeal (FM), but excessive CAP substitutions will affect gut health. Bile acids (BAs) have multiple benefits, but little information is available on the effects of BAs on Pacific white shrimp ( Litopenaeus vannamei ) fed a CAP diet (CAP replacing FM). An 8-week feeding trial were used to investigate the impacts of CAP substitution and BAs addition on structural changes of intestine, apoptosis, inflammatory cytokine and NFκB pathway of intestine, and transcriptomic profiles of hepatopancreas in Pacific white shrimp. Compared to PC (control) treatment, the NC (CAP50, CAP replacing 50% FM) treatment significantly decreased the fold height (FH) and villus length (VL) of midgut, and impaired the mitochondrial cristae. Compared to NC group, the FH was increased in BA1 (CAP50 with 0.03% BAs) and BA2 (CAP50 with 0.06% BAs) groups, the muscle layer thickness (MT) was decreased in BA2 and BA3 (CAP50 with 0.09% BAs) groups, the VL was increased in BA1 group, and the mitochondrial cristae was normal and well-defined in BA1 and BA2 groups (all p < 0.05). The NC increased the genes expression of apoptosis and NFκB signalling pathway, while the BA2 decreased the genes expression of apoptosis, inflammatory cytokine and NFκB signalling pathway. In transcriptomics analysis, a total of 171 differential expression genes (DEGs) were identified in NC group and 50 DEGs in BA2 group. There was 13 DEGs was observed both in NC and BA2 groups. The 5 KEGG pathways were statistically enriched in all treatments, including “Carbon metabolism”, “One carbon pool by folate”, “Glycine, serine and threonine metabolism”, “Amino sugar and nucleotide sugar metabolism”, and “PPAR signaling pathway”. In conclusion, CAP50 substitution impaired the intestinal health and 0.06% BAs addition improved it, both treatments altered the transcriptomics profiles of hepatopancreas in Pacific white shrimp.
研究领域:
水产养殖学
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分子生物学
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营养学
✓ 已验证
产品关联
DOI
高影响因子
Animal Nutrition
·
2025
·
IF 7.5
Qingyan Yin,Xingwei Jiang,Huifeng Liu,Peiyue Wang,Xiaodong Su,Jun Zhang,Xinjian Lei,Junhu Yao
An essential function carried out by bile acids (BA) is to aid in lipid absorption, as they emulsify lipids and combine with them to form chylomicrons. While BA have been utilized as lipid emulsifiers in monogastric and aquatic animals, their impact on ruminants remains relatively unexplored. Two experiments were conducted to investigate the effects of BA on the lipid absorption of lactating dairy goats. In experiment 1, twelve lactating goats with similar days in milk (42 ± 2 d), body weight (46.2 ± 5.1 kg), and milk yield (1.62 ± 0.33 kg) were administered four BA doses (0, 1, 2, or 4 g/d) to explore the effects of BA supplementation. The results observed a positive correlation between the BA dose and plasma total bile acid concentration ( P < 0.001). Notably, when goats received BA, there was a trend of increase in the proportion of preformed fatty acids in milk ( P = 0.079). In experiment 2, eighteen lactating goats with similar days in milk (100 ± 6 d), body weight (45.0 ± 3.7 kg), and milk yield (1.60 ± 0.31 kg) were divided into two groups (HF and HFB): HF group received no BA, while HFB group received BA (4 g/d). Both the groups were fed diets with fat powder supplementation (1% of dry material) for 5 weeks. BA supplementation led to a significant increase in milk yield ( P = 0.024) and fat concentration ( P = 0.045). Meanwhile, there was a significant rise of total bile acid concentration in plasma ( P < 0.001), rumen ( P < 0.001) and feces ( P < 0.001). Additionally, BA supplementation had a significant impact on blood metabolism, up-regulating 241 metabolites and down-regulating 208 metabolites ( P < 0.05). BA supplementation also altered the correlations among various plasma lipid components ( P < 0.05). In fatty acid (FA) analysis, 26 different FA were detected, out of which 16 showed significant down-regulation upon BA supplementation ( P < 0.05). In conclusion, BA supplementation positively influenced lactating dairy goats, particularly when fed diets with fat powder supplementation. BA supplementation enhanced milk yield, improved milk fat concentration, and significantly altered lipid-related blood metabolism. These findings suggest that BA supplementation could be a valuable strategy for enhancing dairy production and lipid metabolism in dairy goats, offering potential benefits for the dairy industry.
研究领域:
动物营养学
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生物化学
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乳品科学
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产品关联
DOI
PubMed
高影响因子
Recent Patents on Anti-Cancer Drug Discovery
·
2021
·Vol. 16
·期 2
·258-272
·
IF 4.169
Zhang Xiangli,Shen Qin,Wang Yi,Zhou Leilei,Weng Qi,Li Qingyong
Background: E2 (Camptothecin - 20 (S) - O- glycine - deoxycholic acid), and G2 (Camptothecin - 20 (S) - O - acetate - deoxycholic acid) are two novel bile acid-derived camptothecin analogues, modified deoxycholic acid at 20-position of CPT(camptothecin) with greater anticancer activity
and lower systematic toxicity in vivo. Objective: We aimed to investigate the metabolism of E2 and G2 by Rat Liver Microsomes (RLM). Methods: Phase I and Phase II metabolism of E2 and G2 in rat liver microsomes were performed, respectively, and the mixed incubation of phase I and
phase II metabolism of E2 and G2 was also processed. Metabolites were identified by liquid chromatographic/mass spectrometry. Results: The results showed that phase I metabolism was the major biotransformation route for both E2 and G2. The isoenzyme involved in their metabolism had some
difference. The intrinsic clearance of G2 was 174.7 mL/min. mg protein, more than three times that of E2 (51.3 mL/min . mg protein), indicating a greater metabolism stability of E2. 10 metabolites of E2 and 14 metabolites of G2 were detected, including phase I metabolites (mainly via hydroxylations
and hydrolysis) and their further glucuronidation products. Conclusion: These findings suggested that E2 and G2 have similar biotransformation pathways except for some differences in the hydrolysis ability of the ester bond and amino bond from the parent compounds, which may result in
the diversity of their metabolism stability and responsible CYPs(Cytochrome P450 proteins).
研究领域:
药理学
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生物化学
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肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Xiaofeng Liu,Yong Zhao,Chenyue Liu,Chunying Li,Yan Yi,Suyan Liu,Xuan Tang,Chen Pan,Yushi Zhang,Jingzhuo Tian,Jiayin Han,Xingnan Yue,Aihua Liang
Ethnopharmacological relevance Psoraleae Fructus (PF), the dried mature fruit of the leguminous plant Psoralea corylifolia L., is often used as a nutraceutical and to treat ulcerative colitis (UC). However, recently there have been reports of PF-induced liver injury. Aim of the study To investigate the difference and mechanism of hepatotoxicity between normal and UC rats oral administration with PF, and clarify the relationship between PF risk and disease status. Materials and Methods PF water extracts (at the human equivalent dosage and 8-fold greater; 0.7 and 5.6 g/kg/day, respectively) were given to normal and UC rats for 4 weeks, and the general behaviors and colonic mucosal conditions were observed. The liver injury and its mechanism were studied by blood biochemistry, coagulation time, liver hematoxylin and eosin (H&E) staining, bile acids (BAs) metabolism, transcriptome analysis, quantitative real-time polymerase chain reaction (qRT‒PCR) and western blot (WB)experiments. Results Normal rats receiving 5.6 g/kg PF water extract showed significantly increased serum levels of total bilirubin (TBIL) and total bile acids (TBA), significantly prolonged activated partial thromboplastin time (APTT), prothrombin time (PT) and thromboplastin time (TT), and slightly swollen hepatocytes, and obvious hepatobiliary hyperplasia. These liver injuries may be related to disordered BAs metabolism: the levels of farnesoid x receptor (FXR) and sulfotransferase family 2A member 1/2 (SULT2a1/a2) were down-regulated, whereas the levels of microsomal epoxide hydrolase (mEH), organic anion transporting polypeptide (OATP) and multidrug resistance-associated protein 3 (MRP3) were up-regulated, leading to liver and blood UnconBA and GlycineBA accumulation. However, at the same dose, UC model rats exhibited no obvious liver damage. Conclusion Normal rats, but not UC rats, displayed signs of liver injury in response to 5.6 g/kg PF water extract administration. Therefore, we recommend that healthy individuals should be aware of the potential risks associated with PF, and other patients should take PF according to their physician’s guidance.
研究领域:
药理学
·
分子生物学
·
中医药学
✓ 已验证
DOI
PubMed
高影响因子
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