Serum, spleen metabolomics and gut microbiota reveals effect of catalpol on blood deficiency syndrome caused by cyclophosphamide and acetylphenylhydrazine
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ABSTRACT:
SUBMITTER: Zhang W
PROVIDER: S-EPMC10655121 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:Background: Farnesoid X receptor (FXR) is a key metabolic target of bile acids (BAs) and is also a target for drugs against several liver diseases. However, the contribution of FXR in the pathogenesis of cholestasis is still not fully understood. The purpose of this study is to provide a comprehensive insight into the metabolic properties of FXR-involved cholestasis in mice. Materials and methods: In this study, an alpha-naphthylisothiocyanate (ANIT)-induced cholestasis mouse model and FXR-/- mice were established to investigate the effect of FXR on cholestasis. The effect of FXR on liver and ileal pathology was evaluated. Simultaneously, Untargeted metabolomics combined with 16s rRNA gene sequencing analysis was applied to reveal the involvement of FXR in the pathogenesis of cholestasis. Results: The results showed that ANIT (75 mg/kg) induced marked cholestasis in WT and FXR -/- mice. It is noteworthy that FXR-/- mice developed spontaneous cholestasis. Compared with WT mice, significant liver and ileal tissue damage were found. In addition, 16s rRNA gene sequencing analysis revealed gut microbiota dysbiosis in FXR-/- mice and ANIT-induced cholestasis mice. Differential biomarkers associated with the pathogenesis of cholestasis caused by FXR knockout were screened using untargeted metabolomics. Notably, Lactobacillus_ johnsonii_FI9785 has a high correlation with the differential biomarkers associated with the pathogenesis and progression of cholestasis caused by FXR knockout. Conclusion: Our results implied that the disorder of the intestinal flora caused by FXR knockout can also interfere with the metabolism. This study provides novel insights into the FXR-related mechanisms of cholestasis.
| S-EPMC10239812 | biostudies-literature
Project description:Pseudostellaria heterophylla, also called Tai-zi-shen (TZS) in Traditional Chinese Medicine (TCM), is always used clinically to treat spleen deficiency symptoms. Polysaccharides in TZS have various pharmacological activities, including anti-diabetic, immune regulation, and myocardial protection. However, the relationship between the spleen-invigorating effects of TZS or its polysaccharides and intestinal flora are not clear. This study investigated the effects of TZS decoction (PHD) and polysaccharide (PHP) on immune function and intestinal flora in a rat model of spleen deficiency syndrome (SDS) induced by a decoction of raw rhubarb (RRD). PHD and PHP increased immune organ index, alleviated inflammatory cell filtration, and reduced the levels of pro-inflammatory cytokines in rats with spleen deficiency syndrome. In addition, the production of butyric acid was promoted in PHD and PHP groups. Moreover, 16S rRNA gene sequencing showed that PHD and PHP reduced the relative abundance of Firmicutes while increasing the one of Bacteroidetes; significantly increased the abundance of Lactobacillus and decreased the abundance of Rombutsia; and PHP significantly increased the abundance of Alloprevotella. And there was a significant positive correlation between the alleviation of SDS and short-chain fatty acids (SCFAs)-producing bacteria. These findings suggested PHD and PHP, especially PHP, has a potential to relieve spleen deficiency by reducing intestinal inflammation, modulating structure and composition of gut microbiota, and promoting the production of butyric acid.
| S-EPMC9684442 | biostudies-literature
Project description:Pingwei San (PWS) has been used for more than a thousand years as a traditional Chinese medicine prescription for treating spleen-deficiency diarrhea (SDD). Nevertheless, the exact mechanism by which it exerts its antidiarrheal effects remains unclear. The objective of this investigation was to explore the antidiarrheal efficacy of PWS and its mechanism of action in SDD induced by Rhubarb. To this end, UHPLC-MS/MS was used to identify the chemical composition of PWS, while the body weight, fecal moisture content, and colon pathological alterations were used to evaluate the effects of PWS on the Rhubarb-induced rat model of SDD. Additionally, quantitative polymerase chain reaction (qPCR) and immunohistochemistry were employed to assess the expression of inflammatory factors, aquaporins (AQPs), and tight junction markers in the colon tissues. Furthermore, 16S rRNA was utilized to determine the impact of PWS on the intestinal flora of SDD rats. The findings revealed that PWS increased body weight, reduced fecal water content, and decreased inflammatory cell infiltration in the colon. It also promoted the expression of AQPs and tight junction markers and prevented the loss of colonic cup cells in SDD rats. In addition, PWS significantly increased the abundance of Prevotellaceae, Eubacterium_ruminantium_group, and Tuzzerella, while decreasing the abundance of Ruminococcus and Frisingicoccus in the feces of SDD rats. The LEfSe analysis revealed that Prevotella, Eubacterium_ruminantium_group, and Pantoea were relatively enriched in the PWS group. Overall, the findings of this study indicate that PWS exerted a therapeutic effect on Rhubarb-induced SDD in rats by both protecting the intestinal barrier and modulating the imbalanced intestinal microbiota.
| S-EPMC10215682 | biostudies-literature
Project description:BackgroundTaohong Siwu Decoction (THSWD) is a prescription which included in the "List of Ancient Classic Prescriptions (First Batch)" issued by the National Administration of Traditional Chinese Medicine (TCM) and the National Medical Products Administration of the People's Republic of China. THSWD is effective and widely applied clinically for many diseases caused by blood deficiency and stasis syndrome in TCM, such as primary dysmenorrhea, menopausal syndrome, coronary heart disease, angina pectoris, and diabetes.MethodsThe TCM model of blood deficiency and blood stasis syndrome was prepared by ice water bath combined with cyclophosphamide, and the rats were randomly divided into control group, blood deficiency, and blood stasis model group, positive group, and THSWD treatment group. Pharmacodynamics measured the blood routine, blood coagulation, and other related indexes in rats. UHPLC-MS technology was used to analyze the changes in the fingerprints of metabolites in the plasma of rats with blood deficiency and blood stasis syndrome, and combined with mass spectrometry information and public database retrieval, to find potential biomarkers for screening metabolites. At the same time, 16S rDNA sequencing technology was used to identify intestinal flora, and statistical analysis was used to find differences in strain diversity between groups.ResultsTHSWD administration can significantly improve the physical signs, blood routine, and hematopoietic factors caused by the blood deficiency and blood stasis syndrome model, and improve the symptoms of blood deficiency. The results of the general pharmacological studies showed THSWD groups improved changes in blood plasma viscosity and coagulation-related factors caused by modeling, and improved coagulation function significantly. The metabolomic analysis found that compared to the model group, THSWD exerted better effects on β-alanine, taurine, L-tyrosine, L-arginine, Eugenol, sodium deoxycholate, and deethylatrazine. Twenty-three potential differential metabolites showed intervention effects, mainly involved in eight metabolic pathways, including amino acid metabolism, taurine and hypotaurine metabolism, vitamin metabolism, and nucleotide metabolism. Gut microbiota data showed that, compared to the control group, the relative abundance and value of Firmicutes and Bacteroidota of the blood deficiency and blood stasis model group was significantly reduced, while the relative abundance of Actinobacteria, Spirochaetota, Proteobacteria, Campilobacterota, and other pathogenic bacteria was significantly increased. Following THSWD intervention, the abundance of beneficial bacteria increased, and the abundance of pathogenic bacteria decreased. Correlation analysis between the gut microbiota and differential metabolites showed that the two are closely related. THSWD affected the host blood system through mutual adjustment of these two factors, and improved blood deficiency and blood stasis syndrome in rats.ConclusionThe blood deficiency and blood stasis syndrome model of TCM disease caused by ice bath combined with cyclophosphamide lead to changes in the pharmacology, metabolomics, and gut microbiota. The intervention of THSWD can improve the symptoms caused by blood deficiency and blood stasis. The mechanism is mainly through the regulation of platelet function and amino acid metabolism.
| S-EPMC10122815 | biostudies-literature
Project description:BackgroundSimo decoction (SMD) is a traditional prescription for treating gastrointestinal diseases. More and more evidences prove that SMD can treat constipation by regulating intestinal microbiota and related oxidative stress indicators, but the specific mechanism is still unclear.MethodsA network pharmacological analysis was used to predict the medicinal substances and potential targets of SMD to alleviate constipation. Then, 15 male mice were randomly divided into normal group (MN group), natural recovery group (MR group), and SMD treatment group (MT group). Constipation model mice were constructed by gavage of Folium sennae decoction and control of diet and drinking water, and SMD was used for intervention after successful modeling. The levels of 5-hydroxytryptamine (5-HT), vasoactive intestinal peptide (VIP), superoxide dismutase (SOD), malondialdehyde (MDA), and fecal microbial activities were measured, and the intestinal mucosal microbiota was sequenced.ResultNetwork pharmacology analysis showed that a total of 24 potential active components were obtained from SMD, and 226 target proteins were obtained after conversion. Meanwhile, we obtained 1,273 and 424 disease-related targets in the GeneCards database and the DisGeNET database, respectively. After combination and deduplication, the disease targets shared 101 targets with the potential active components of SMD. When the mice were intervened with SMD, the 5-HT, VIP, MDA, SOD content, and microbial activity in MT group were close to MN group, and Chao 1 and ACE in MT group were significantly higher than that in MR group. In the Linear discriminant analysis Effect Size (LEfSe) analysis, the abundance of beneficial bacteria such as Bacteroides, Faecalibacterium, Alistipes, Subdoligranulum, Lactiplantibacillus, and Phascolarctobacterium in MT group increased. At the same time, there were some associations between microbiota and brain-gut peptides and oxidative stress indicators.ConclusionSMD can promote intestinal health and relieve constipation through brain-bacteria-gut axis associating with intestinal mucosal microbiota and alleviate oxidative stress.
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Project description:BackgroundDysregulation of gut microbiota-host bile acid (BA) co-metabolism is a critical pathogenic factor of diarrhea-predominant irritable bowel syndrome (IBS-D). Traditional Chinese Medicine (TCM), instructed by pattern differentiation, is effective in treating IBS-D, in which liver depression and spleen deficiency (LDSD) is the most prevalent pattern. Still, it is unclear the linkage between the LDSD pattern and the BA metabolic phenotype.PurposeThis study aimed to uncover the biological basis of the LDSD pattern from the BA metabolic perspective.MethodsPatients with IBS-D completed questionnaires regarding the irritable bowel severity scoring system (IBS-SSS), stool frequency, Stool Bristol scale, and Self-Rating Scales of mental health. Fasting blood and morning feces were collected to analyze the gut metagenome and BA-related indices/metabolites.ResultsIBS-D patients with LDSD had a higher incidence of BA overexcretion (41% vs. 23% non-LDSD) with significant elevations in fecal total BAs and serum BA precursor 7α-hydroxy-4-cholesten-3-one levels. Compared to controls or non-LDSD patients, LDSD patients had a featured fecal BA profile, with higher proportions of deoxycholic acid (DCA), 7-ketodeoxycholic acid, and lithocholic acid. It is consistent with the BA-metabolizing genomic changes in the LDSD gut microbiota characterized by overabundances of 7-dehydroxylating bacteria and BA-inducible genes (baiCD/E/H). The score of bowel symptoms (stool frequency and abdominal pain) showing greater severity in the LDSD pattern were positively correlated with bai-expressing bacterial abundances and fecal DCA levels separately.ConclusionWe clarified a differed BA metabolic phenotype in IBS patients with LDSD, which closely correlates with the severity of bowel symptoms. It demonstrates that gut microbiota and host co-metabolism of BAs would provide crucial insight into the biology of the LDSD pattern and its internal relationship with IBS progression.
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Project description:Codonopsis Radix (CR) is an important traditional Chinese medicine used for the treatment of spleen deficiency syndrome (SDS). Codonopsis pilosula polysaccharides (CPP) in CR are considered to be responsible for tonifying the spleen function; however, the mechanisms of the polysaccharides have remained unclear. This study aimed to investigate the treatment mechanisms of CPP in SDS mice using a combinational strategy of 16S rRNA gene sequencing and targeted metabolomics. Here, studies demonstrated that CPP had invigorating effect in vivo in Sennae Folium-induced SDS in mice by organ indexes, D-xylose determination, gastrointestinal hormones levels and goblet cells observation. Antibiotic treatment revealed that the intestinal microbiota was required for the invigorating spleen effect of CPP. Furthermore, gut microbiota analysis found that CPP significantly enriched probiotic Lactobacillus and decreased the abundance of some opportunistic pathogens, such as Enterococcus and Shigella. The metabolic profile analysis of the colonic content revealed that 25 chemicals were altered significantly by CPP, including amino acids, organic acids, fatty acids, carbohydrates and carnitine etc., which are mainly related to "energy conversion" related processes such as amino acids metabolism, tricarboxylic acid cycle, and nitrogen metabolism. Spearman's correlation assays displayed there were strong correlations among biochemical indicators-gut microbiota-metabolomics. In summary, these results provided a new perspective for CPP improving SDS by regulating energy metabolism related bacteria and pathways.
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Project description:Fecal microbiota transplantation (FMT) is an effective means of modulating gut microbiota for the treatment of many diseases, including Clostridioides difficile infections. The gut-spleen axis has been established, and this is involved in the development and function of the spleen. However, it is not understood whether gut microbiota can be used to improve spleen function, especially in spleens disrupted by a disease or an anti-cancer treatment. In the current investigation, we established that alginate oligosaccharide (AOS)-improved gut microbiota (A10-FMT) can rescue anticancer drug busulfan-disrupted spleen vasculature and spleen function. A10-FMT improved the gene and/or protein expression of genes involved in vasculature development, increased the cell proliferation rate, enhanced the endothelial progenitor cell capability, and elevated the expression of the cell junction molecules to increase the vascularization of the spleen. This investigation found for the first time that the reestablishment of spleen vascularization restored spleen function by improving spleen immune cells and iron metabolism. These findings may be used as a strategy to minimize the side effects of anti-cancer drugs or to improve spleen vasculature-related diseases. IMPORTANCE Alginate oligosaccharide (AOS)-improved gut microbiota (A10-FMT) can rescue busulfan disrupted spleen vasculature. A10-FMT improved the cell proliferation rate, endothelial progenitor cell capability, and cell junction molecules to increase vasculature formation in the spleen. This reestablishment restored spleen function by improving spleen immune cells and iron metabolism. These findings are useful for the treatment of spleen vasculature-related diseases.
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Project description:This study evaluated the performance, gut microbiota, and blood metabolites in broiler chickens fed cranberry and blueberry products for 30 days. A total of 2,800 male day-old broiler Cobb-500 chicks were randomly distributed between 10 diets: control basal diet; basal diet with bacitracin (BACI); four basal diets with 1 and 2% of cranberry (CP1, CP2) and blueberry (BP1, BP2) pomaces; and four basal diets supplemented with ethanolic extracts of cranberry (COH150, COH300) or blueberry (BOH150, BOH300) pomaces. All groups were composed of seven replicates (40 birds per replicate). Cecal and cloacal samples were collected for bacterial counts and 16S rRNA gene sequencing. Blood samples and spleens were analyzed for blood metabolites and gene expressions, respectively. The supplementation of COH300 and BOH300 significantly increased the body weight (BW) during the starting and growing phases, respectively, while COH150 improved (P < 0.05) the overall cumulated feed efficiency (FE) compared to control. The lowest prevalence (P = 0.01) of necrotic enteritis was observed with CP1 and BP1 compared to BACI and control. Cranberry pomace significantly increased the quinic acid level in blood plasma compared to other treatments. At days 21 and 28 of age, the lowest (P < 0.05) levels of triglyceride and alanine aminotransferase were observed in cranberry pomace and blueberry product-fed birds, respectively suggesting that berry feeding influenced the lipid metabolism and serum enzyme levels. The highest relative abundance of Lactobacillaceae was found in ceca of birds fed CP2 (P < 0.05). In the cloaca, BOH300 significantly (P < 0.005) increased the abundances of Acidobacteria and Lactobacillaceae. Actinobacteria showed a significant (P < 0.05) negative correlation with feed intake (FI) and FE in COH300-treated birds, whereas Proteobacteria positively correlated with the BW but negatively correlated with FI and FE, during the growing phase. In the spleen, cranberry products did not induce the release of any pro-inflammatory cytokines but upregulated the expression of several genes (IL4, IL5, CSF2, and HMBS) involved in adaptive immune responses in broilers. This study demonstrated that feed supplementation with berry products could promote the intestinal health by modulating the dynamics of the gut microbiota while influencing the metabolism in broilers.
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Project description:The impact of 4-epi-oxytetracycline (4-EOTC), one of the main oxytetracycline (OTC) metabolites, on the gut microbiota and physiological metabolism of Wistar rats was analyzed to explore the dynamic alterations apparent after repeated oral exposure (0.5, 5.0 or 50.0 mg/kg bw) for 15 days as shown by 16S rRNA pyrosequencing and UPLC-Q-TOF/MS analysis. Both principal component analysis and cluster analysis showed consistently altered patterns with distinct differences in the treated groups versus the control groups. 4-EOTC treatment at 5.0 or 50.0 mg/kg increased the relative abundance of the Actinobacteria, specifically Bifidobacteriaceae, and improved the synthesis of lysophosphatidylcholine (LysoPC), as shown by the lipid biomarkers LysoPC(16:0), LysoPC(18:3), LysoPC(20:3), and LysoPC(20:4). The metabolomic analysis of urine samples also identified four other decreased metabolites: diacylglycerol, sphingomyelin, triacylglycerol, and phosphatidylglycerol. Notably, the significant changes observed in these biomarkers demonstrated the ongoing disorder induced by 4-EOTC. Blood and urine analysis revealed that residual 4-EOTC accumulated in the rats, even two weeks after oral 4-EOTC administration, ceased. Thus, through thorough analysis, it can be concluded that the alteration of the gut microbiota and disorders in blood metabolomics are correlated with 4-EOTC treatment.
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