Gut Pathogens
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2023
·Vol. 15
·期 1
·1-14
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IF 4.2
Wang Shanshan,Wen Qiuyu,Qin Yan,Xia Quan,Shen Chenlin,Song Shuai
Background The pseudo germ-free (PGF) model has been widely used to research the role of intestinal microbiota in drug metabolism and efficacy, while the modelling methods and the utilization of the PGF model are still not standardized and unified. A comprehensive and systematic research of the PGF model on the composition and function of the intestinal microbiota, changes in host cytochrome P450 (CYP450) enzymes expression and intestinal mucosal permeability in four different modelling cycles of the PGF groups are provided in this paper.Results 16S rRNA gene amplicon sequencing was employed to compare and analyze the alpha and beta diversity, taxonomic composition, taxonomic indicators and predicted function of gut microbiota in the control and PGF groups. Bacterial richness and diversity decreased significantly in the PGF group beginning after the first week of establishment of the PGF model with antibiotic exposure. The PGF group exposed to antibiotics for 4-week-modelling possessed the fewest indicator genera. Moreover, increased intestinal mucosal permeability occurred in the second week of PGF model establishment, indicating that one week of antibiotic exposure is an appropriate time to establish the PGF model. The results of immunoblots revealed that CYP1A2, CYP2C19 and CYP2E1 expression was significantly upregulated in the PGF group compared with the control group, implying that the metabolic clearance of related drugs would change accordingly. The abundance of functional pathways predicted in the gut microbiota changed dramatically between the control and PGF groups.Conclusion sThis study provides information concerning the microbial and CYP450 enzyme expression profiles as a reference for evaluating drug metabolism differences co-affected by gut microbiota and host CYP450 enzymes in the PGF model.
研究领域:
药理学
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微生物学
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分子生物学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
Drug Metabolism and Pharmacokinetics
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2022
·
IF 2.041
Shanshan Wang,Yan Qin,Qiuyu Wen,Quan Xia,Ruoyu Gu,Sheng Wang,GuanJun Chen,Chao Tan,Chenlin Shen,Shuai Song
Adverse reactions to azathioprine (AZA) vary greatly among individuals, which is associated with the variable levels of its major metabolites 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP). The intestinal microbiota has been proven to contain AZA-metabolizing enzymes, although the explicit role of the intestinal microbiota in AZA metabolism in vivo remains poorly comprehended. In this study, the pharmacokinetic behaviours of 6-TGN and 6-MMP were assessed in the pseudo germ-free (PGF) group and control group following oral administration of AZA. The AUC 0-t and C max of 6-TGN in the PGF group were significantly decreased by 34.0% and 35.0% ( P < 0.05) compared with those in the control group. Additionally, the AUC 0-t and C max of 6-MMP were reduced by 27.9% and 34.2% in the PGF group, although the differences were not significant. The TPMT and NUDT15 genotypes of rats in the two groups were genetically identical. The expression levels of key AZA-metabolizing enzymes in liver were not different between two groups. Furthermore, the major metabolites of AZA in the incubation system with intestinal microbial enzymes were identified. In summary, shifts in the composition of the intestinal microbiota may regulate the exposure of 6-TGN in vivo by altering the gut microbial metabolism of AZA.
研究领域:
药理学
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微生物学
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药物基因组学
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2022
·Vol. 13
·期 13
·7274-7286
·
IF 6.317
Zhijing Wu,Yu Zhang,Gang Nie,Junxi Liu,Hao Mei,Zihao He,Pengfei Dou,Kaiping Wang
Recently, Dendrobium officinale polysaccharide (DOP), a typical acetylated glucomannan, has been widely applied in functional foods owing to its excellent bioactivity. However, the insufficiency of studies on in vivo process severely limits the further utilization of DOP. The aim of this study was to systematically investigate the gastrointestinal digestive behaviour of DOP after oral administration by labelling it with two fluorescein aminopyrene-1,3,6-trisulfonic acids, trisodium salt (APTS) and cyanine 7.5 (Cy7.5). Combining the results of NIR imaging and HPGPC, we found that DOP was poorly absorbed directly in the prototype form; instead, DOP moved with the intestinal contents to the distal part of the intestine, where Bacteroides aggregated for a prolonged time and was metabolized to oligosaccharide-like substances. In contrast, the digestive degradation of DOP in pseudo-sterile mice with a targeted clearance of Bacteroides significantly weakened, which provided the basis and direction for the subsequent search for more specific metabolic pathways of DOP in vivo.
研究领域:
食品科学
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营养学
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微生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Chinese Journal of Natural Medicines
·
2023
·
IF 4.6
Jianghui HU,Jimin NI,Junping ZHENG,Yanlei GUO,Yong YANG,Cheng YE,Xiongjie SUN,Hui XIA,Yanju LIU,Hongtao LIU
Traditionally, Tripterygium hypoglaucum (Levl.) Hutch (THH) are widely used in Chinese folk to treat rheumatoid arthritis (RA). This study aimed to investigate whether the anti-RA effect of THH is related with the gut microbiota. The main components of prepared THH extract were identified by HPLC-MS. C57BL/6 mice with adjuvant-induced arthritis (AIA) were treated with THH extract by gavage for one month. THH extract significantly alleviated swollen ankle, joint cavity exudation, and articular cartilage destruction in AIA mice. The mRNA and protein levels of inflammatory mediators in muscles and plasma indicated that THH extract attenuated inflammatory responses in the joint by blocking TLR4/MyD88/MAPK signaling pathways. THH extract remarkably restored the dysbiosis of the gut microbiota in AIA mice, featuring the increases of Bifidobacterium , Akkermansia , and Lactobacillus and the decreases of Butyricimonas , Parabacteroides , and Anaeroplasma . Furthermore, the altered bacteria were closely correlated with physiological indices and drove metabolic changes of the intestinal microbiota. In addition, antibiotic-induced pseudo germ-free mice were employed to verify the role of the intestinal flora. Strikingly, THH treatment failed to ameliorate the arthritis symptoms and signaling pathways in pseudo germ-free mice, which validates the indispensable role of the intestinal flora. For the first time, we demonstrated that THH extract protects joint inflammation by manipulating the intestinal flora and regulating the TLR4/MyD88/MAPK signaling pathway. Therefore, THH extract may serve as a microbial modulator to recover RA in clincial practice.ver RA in clincial practice.
研究领域:
药理学
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免疫学
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微生物学
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风湿病学
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产品关联
DOI
PubMed
高影响因子
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