A diverse range of symbiotic gut bacteria codevelops with the host and is considered a metabolic “organ” that not only facilitates harvesting of nutrients from the dietary components but also ...produces a class of metabolites. Many metabolites of gut microbes have an important impact on host health. For example, an inventory of metabolic intermediates derived from bacterial protein fermentation may affect host physiology and pathophysiology. Additionally, gut microbiota can convert cholesterol to bile acids and further into secondary bile acids which can conversely modulate microbial community. Moreover, new research identifies that microbes synthesize vitamins for us in the colon. Here, we will review data implicating a major class of bacterial metabolites through breaking down dietary fiber we cannot process, short-chain fatty acids (SCFAs), as crucial executors of alteration of immune mechanisms, regulation of metabolic homeostasis, and neuroprotective effects to combat disease and improve health.
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CEKLJ, DOBA, EMUNI, FZAB, GEOZS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Scutellariae radix (
Scutellaria baicalensis
Georgi, SR) and coptidis rhizoma (
Coptis chinensis
Franch, CR) are both widely used traditional Chinese medicines and have been used together to treat ...T2DM with synergistic effects in the clinical practices for thousands of years, but their combination mechanism is not clear. Accumulating evidences have implicated gut microbiota as important targets for the therapy of T2DM. Thus, this study aimed to unravel the cooperation mechanism of SR and CR on the amelioration of T2DM based on the systematic analysis of metagenome and metabolome of gut microbiota. Bacterial communities were analyzed based on high-throughput 16S rRNA gene sequencing. Furthermore, ultra high-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS) was used to analyze variations of microbial metabolites in feces and the contents of short chain fatty acids (SCFAs) in the cecum were determined by a gaschromatography-flame ionization detector (GC-FID). 16S rRNA gene sequencing results revealed that T2DM rats treated with SR, CR, and the combination of SR and CR (SC) exhibited changes in the composition of the gut microbiota. The SCFAs-producing bacteria such as
Bacteroidales S24-7 group_norank
,
Eubacterium nodatum group
,
Parasutterella
,
Prevotellaceae UCG-001
,
Ruminiclostridium
, and
Ruminiclostridium 9
in T2DM rats were notably enriched after treatment with SR, CR, and their combination. In contrast, secondary bile acid-producing bacteria such as
Escherichia-Shigella
strongly decreased in numbers. The perturbance of metabolic profiling in T2DM rats was obviously improved after treatment, exhibiting a lower level of secondary bile acids and a numerical increase of microbially derived SCFAs. Moreover, the correlation analysis illustrated a close relationship among gut microbiota, its metabolites, and T2DM-related indexes. The findings indicated that the crosstalk between microbiota-derived metabolites and the host played an important role in the progress of T2DM and might provide a novel insight regarding gut microbiota and its metabolites as potential new targets of traditional Chinese medicines. Furthermore, this work also suggested that the integration of various omics methods and bioinformatics made a useful template for drug mechanism research.
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CEKLJ, DOBA, EMUNI, FZAB, GEOZS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Rhubarb, a traditional herb, has been used in clinical practice for hundreds of years to cure constipation, but its mechanism is still not clear enough. Currently, growing evidence suggests that ...intestinal flora might be a potential target for the treatment of constipation. Thus, the aim of this study was to clarify the laxative effect of rhubarb via systematically analyzing the metagenome and metabolome of the gut microbiota. In this study, the laxative effects of rhubarb were investigated by loperamide-induced constipation in rats. The gut microbiota was determined by high-throughput sequencing of 16S rRNA gene. Ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used for fecal metabolomics analysis. The data showed that rhubarb could significantly shorten gastrointestinal transit time, increase fecal water content and defecation frequency, improve gastrointestinal hormone disruption, and protect the colon mucus layer. Analysis of 16S rRNA gene sequencing indicated that rhubarb could improve the disorder of intestinal microbiota in constipated rats. For example, beneficial bacteria such as
Ligilactobacillus
,
Limosilalactobacillus
, and
Prevotellaceae UCG-001
were remarkably increased, and pathogens such as
Escherichia-Shigella
were significantly decreased after rhubarb treatment. Additionally, the fecal metabolic profiles of constipated rats were improved by rhubarb. After rhubarb treatment, metabolites such as chenodeoxycholic acid, cholic acid, prostaglandin F2α, and α-linolenic acid were markedly increased in constipation rats; in contrast, the metabolites such as lithocholic acid, calcidiol, and 10-hydroxystearic acid were notably reduced in constipation rats. Moreover, correlation analysis indicated a close relationship between intestinal flora, fecal metabolites, and biochemical indices associated with constipation. In conclusion, the amelioration of rhubarb in constipation might modulate the intestinal microflora and its metabolism. Moreover, the application of fecal metabolomics could provide a new strategy to uncover the mechanism of herbal medicines.
Key points
•
Rhubarb could significantly improve gut microbiota disorder in constipation rats.
•
Rhubarb could markedly modulate the fecal metabolite profile of constipated rats.
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CEKLJ, DOBA, EMUNI, FZAB, GEOZS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
•Three types of metabolites were analysed in jujube fruits at 6 ripening stages.•The contents of most triterpenoids and sugars increased with jujube fruit ripening.•The accumulation of cAMP and cGMP ...was mainly in the later stage of ripening.•The results will be helpful to determine the harvest time for jujube fruit.
Jujube (Ziziphus jujuba) fruit is widely consumed as food and traditional Chinese medicine in Asian countries due to its potential effects for human health. To facilitate selection of the maturity stage providing optimum health benefits, jujube fruits were analysed at six stages of growth (S1–6) for triterpenic acids, nucleosides, nucleobases, and sugars by UHPLC–MS/MS or HPLC–ELSD methods. The content levels of most triterpenic acids and sugars increased with ripening, and reached the highest at S5 and S6, respectively. The accumulation of the cyclic nucleotides (cAMP and cGMP) was mainly in the later stage of ripening (S5–6). Therefore, if taking triterpenic acids as the major quality indicator, S5 should be the ideal time to harvest jujube fruit, and the full ripen stage (S6) maybe the best choice when taking sugars and cyclic nucleotides as the most important components.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Ulcerative colitis (UC), a kind of inflammatory bowel disease, is generally characterized by chronic, persistent, relapsing, and nonspecific ulceration of the bowel, which is widespread in the world. ...Although the pathogenesis of UC is multifactorial, growing evidence has demonstrated that gut microbiota and its metabolites are closely related to the development of UC. Lizhong decoction (LZD), a well-known classical Chinese herbal prescription, has been used to clinically treat UC for long time, but its mechanism is not clear. In this study, 16S rRNA gene sequencing combining with untargeted metabolomics profiling was used to investigate how LZD worked. Results indicated that LZD could shape the gut microbiota structure and modify metabolic profiles. The abundance of opportunistic pathogens such as
Clostridium
sensu stricto
1
,
Enterobacter
, and
Escherichia-Shigella
correlated with intestinal inflammation markedly decreased, while the levels of beneficial bacteria including
Blautia
,
Muribaculaceae_norank
,
Prevotellaceae UCG-001
, and
Ruminiclostridium 9
elevated in various degrees. Additionally, fecal metabolite profiles reflecting microbial activities showed that adenosine, lysoPC(18:0), glycocholic acid, and deoxycholic acid notably decreased, while cholic acid, α-linolenic acid, stearidonic acid, and
l
-tryptophan significantly increased after LZD treatment. Hence, based on the systematic analysis of 16S rRNA gene sequencing and metabolomics of gut flora, the results provided a novel insight that microbiota and its metabolites might be potential targets for revealing the mechanism of LZD on amelioration of UC.
Key Points
•
The potential mechanism of LZD on the amelioration of UC was firstly investigated.
•
LZD could significantly shape the structure of gut microbiota.
•
LZD could notably modulate the fecal metabolic profiling of UC mice.
Graphical abstract
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CEKLJ, DOBA, EMUNI, FZAB, GEOZS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In this study, a sensitive and rapid method for the simultaneous determination of free amino acids without derivatization using hydrophilic interaction liquid chromatography coupled with tandem mass ...spectrometry (HILIC–MS/MS) was developed. The method was performed on an ultra-high-performance liquid chromatography (UHPLC) separation system coupled with a triple-quadrupole mass spectrometry (TQ-MS) instrument. Sufficient separation of 23 underivatized amino acids was achieved on an Acquity BEH Amide column (2.1 mm × 100 mm, 1.7 μm) in a single run of 12 min. Then the method was applied for the analysis of the free amino acids in 46 batches of Ziziphus jujuba fruits which comprised 39 cultivars from 26 cultivation regions. Multivariate statistical analysis was also used to investigate the differences in free amino acid profiles among the samples. This study showed that HILIC–UHPLC–TQ-MS is an effective technique to analyze underivatized amino acids in the food samples.
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IJS, KILJ, NUK, PNG, UL, UM, UPUK
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•The components can hypoglycemic and alleviate associated liver and kidney injury.•The effects are related to insulin receptor and TGF-β/Smads signaling pathway.•The components can ...regulate 13 potential biomarkers and 3 metabolism pathway.
Mulberry leaf is one of the commonly used traditional Chinese medicines, has been shown to exert hypoglycemic effects against diabetes. The aim of this study is to investigate the effects and mechanism of mulberry leaf flavonoids (MF), polysaccharides (MP) and alkaloids (MA) on diabetic and its liver and kidney injury. The db/db mice was adopted and the results showed that the FBG (fasting blood glucose) of model group continued to increase and associated liver and kidney injury. After the intervention of MP and MA, the value of FBG exhibited the most obvious hypoglycemic effect. MF and MP have obvious improved effect on kidney injury, which reduced the content of mALB/Cre (microalbumin/creatinine) in urine and improved the tubular epithelial cells edematous and renal cystic epithelial thickening. While the MF and MA possessed a significant effect on liver damage, manifested in reducing the levels of ALT (alanine aminotransferase) and AST (aspartate aminotransferase) and pathological changes of liver on db/db mice. Through metabolomics analysis, 13 endogenous potential biomarkers were identified in serum. The three effective components of mulberry can regulate the 13 potential biomarkers and the corresponding metabolic pathway. Collectively, the components of mulberry leaf have clear hypoglycemic effect and protective effect on liver and kidney injury and the effects are related to insulin receptor and TGF-β/Smads signaling pathway.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•An HILIC–UHPLC-TQ-MS for determination of nucleosides, nucleobases and nucleotides.•Nucleotides could have good retentions and peak shapes with the proposed method.•The method is simple, rapid and ...sensitive than the previous methods.•The method was successfully applied to analysis of Ziziphus plants.
In this study, a rapid and sensitive analytical method was developed for the determination of 20 nucleobases, nucleosides and nucleotides in Ziziphus plants at trace levels by using hydrophilic interaction ultra-high performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry (HILIC–UHPLC-TQ-MS/MS) in multiple-reaction monitoring (MRM) mode. Under the optimized chromatographic conditions, good separation for 20 target compounds were obtained on a UHPLC Amide column with sub-2μm particles within 10min. The overall LODs and LOQs were between 0.11–3.12ngmL−1 and 0.29–12.48ngmL−1 for the 20 analytes, respectively. It is the first report about simultaneous analysis of nucleobases, nucleosides and nucleotides in medicinal plants using HILIC–UHPLC-TQ-MS/MS method, which affords good linearity, precision, repeatability and accuracy. The developed method was successfully applied to Ziziphus plant (Z. jujuba, Z. jujuba var. spinosa and Z. mauritiana) samples. The analysis showed that the fruits and leaves of Ziziphus plants are rich in nucleosides and nucleobases as well as nucleotides, and could be selected as the healthy food resources. Our results in present study suggest that HILIC–UHPLC-TQ-MS/MS method could be employed as a useful tool for quality assessment of the samples from the Ziziphus plants as well as other medicinal plants or food samples using nucleotides, nucleosides and nucleobases as markers.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
•Comprehensive metabolomics approach by UHPLC–QTOF/MS coupled with pattern recognition methods.•Hematopoietic functions of herb pair Gui-Xiong.•Thirteen endogenous metabolites were tentatively ...identified and 12 metabolic pathways were found.•Danggui and Chuanxiong had synergetic hematopoietic effect.
The compatibility of Angelicae Sinensis Radix (Danggui, DG) and Chuanxiong Rhizoma (Chuanxiong, CX), a famous herb pair Gui-Xiong (GX), can produce synergistic and complementary hematopoiesis. In present study, global metabolic profiling with ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC–QTOF/MS) combined with pattern recognition method was performed to discover the underlying hematopoietic regulation mechanisms of DG, CX and GX on hemolytic and aplastic anemia rats (HAA) induced by acetyl phenylhydrazine (APH) and cyclophosphamide (CP). Thirteen endogenous metabolites contributing to the separation of model group and control group were tentatively identified. The levels of LPCs including lysoPC (18:0), lysoPC (20:4), lysoPC (16:0) and lysoPC (18:2), sphinganine, nicotinic acid, thiamine pyrophosphate, phytosphingosine, and glycerophosphocholine increased significantly (p<0.05) in HAA, while the levels of oleic acid, 8,11,14-eicosatrienoic acid, ceramides (d18:1/14:0), and 17a-hydroxypregnenolone decreased significantly (p<0.05) in comparison with control rats. Those endogenous metabolites were chiefly involved in thiamine metabolism and sphingolipid metabolism. The metabolic deviations could be regulated closer to normal level after DG, CX and GX intervention. In term of hematopoietic function, GX was the most effective as shown by the relative distance in PLS-DA score plots and relative intensity of metabolomic strategy, reflecting the synergic action between DG and CX. The relative distance calculation was firstly used in metabolomics for semi-quantization.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The seeds of Sophora alopecuroides L. have been utilized as a crude drug in China for thousands of years. Quinolizidine alkaloids are the main bioactive components of this plant. To determine the ...distribution and content of quinolizidine alkaloids in different seed organs (seed coat and cotyledon), a reliable method has been established using ultra-high-performance liquid chromatography coupled with a triple quadrupole electrospray tandem mass spectrometry (UPLC–MS/MS). Seven constituents, namely cytisine, oxymatrine, oxysophocarpine, sophoridine, sophoramine, matrine, and sophocarpine, were simultaneously determined in 10min. The proposed method was fully validated in terms of linearity, sensitivity, precision, repeatability as well as recovery. The analysis results showed there were remarkable differences in the distribution and contents of the chemical markers between seed coat and cotyledon. The established approach could be helpful for the quality control of S. alopecuroides seeds, and also for the determination of this type class of alkaloids in other medicinal herbs. The present study can provide necessary information for the rational utilization of S. alopecuroides resources.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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