INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Benyue Sun,Wenwen Xie,Xuejiao Li,Taohua Liu,Jingjing Bai,Yuan Yao,Long Ma,Shuli Man
Inulin as a natural polysaccharide regulates intestinal microorganisms, and improves the immune and gastrointestinal function. In order to explore the effect of inulin on pulmonary metastasis of colon cancer, we set up a CT26 injected pulmonary metastatic model. The results showed that inulin used alone did not improve pulmonary metastasis of colon cancer, while inulin combined with rifaximin significantly prolonged the survival time of mice, and inhibited pulmonary metastasis compared with model and inulin groups. Inulin treatment increased the abundance of harmful bacteria such as Proteobacteria and Actinobacteria , while combined treatment decreased their abundance and increased the abundance of beneficial bacteria containing Firmicutes and Eubacterium which belonged to the bile acid-related bacteria. The combination treatment decreased the content of primary bile acids and secondary bile acids in the feces of mice, especial for DCA and LCA which were the agonists of TGR5. Furthermore, the combination treatment reduced the mRNA expression of the TGR5, cyclin dependent kinase 4, cyclin 1 and CDK2, increased the mRNA expression of p21 in the lung, down-regulated the level of NF-κB p65, and up-regulated the level of TNF-α compared with the model group. The above may be the reason for the better use of the combination treatment.
研究领域:
肿瘤学
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微生物学
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免疫学
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药理学
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PubMed
高影响因子
Translational Pediatrics
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2025
·Vol. 14
·期 6
·1213
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IF 1.7
Zihong Shan,Chenghui He,Qingyao Yang,Jingjing Xiong,Meng Li,Mingyao Meng,Yongkun Huang
Background Previous research has indicated that chenodeoxycholic acid (CDCA) plays a significant role in intestinal motility and is implicated in some gastrointestinal (GI) disorders. However, the impact of CDCA on defecation patterns in infants, particularly those who are breastfed, remains unclear. This study explored the relationship between CDCA and defecation frequency in breastfed infants, focusing on the underlying mechanisms. Methods We measured CDCA levels in stool samples of infants with varying defecation frequencies using metabolomics, along with studies to explore the impact of CDCA on murine colonic transit and with in vitro cellular studies to elucidate the underlying physiological mechanisms. Results In our murine model, CDCA treatment increased GI transit distance, enhanced fecal water content, and reduced transit time, without causing significant colonic damage. Additionally, CDCA treatment enhanced 5-hydroxytryptamine (5-HT) secretion and upregulated signaling molecules such as tryptophan hydroxylase 1 (Tph1), G protein-coupled bile acid receptor 1 (TGR5), and transient receptor potential ankyrin 1 (TRPA1). Selective inhibition of these pathways suppressed 5-HT secretion and normalized intestinal motility parameters, confirming their mechanistic role. Moreover, CDCA treatment of rat insulinoma-derived RIN-14B cells also resulted in increased 5-HT secretion. Conclusions These findings reveal that CDCA significantly correlates with defecation frequency in breastfed infants and likely influences intestinal motility through the TGR5/TRPA1-5-HT signaling axis.
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Nutrients
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2023
·Vol. 15
·期 23
·4929
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IF 5.9
Lin Zhu,Shuaizhen Fang,Hong Zhang,Xiangjun Sun,Puyu Yang,Jianchun Wan,Yaqiong Zhang,Weiying Lu,Liangli Yu
In this study, the impact ofsn-2 palmitic triacyclglycerols (TAGs) in combination with their ratio of two major TAGs (1-oleoyl-2-palmitoyl-3-linoleoylglycerol (OPL) to 1,3-dioleoyl-2-palmitoylglycerol (OPO)) in human milk fat substitute (HMFS) on bile acid (BA) metabolism and intestinal microbiota composition was investigated in newly-weaned Sprague–Dawley rats after four weeks of high-fat feeding. Compared to those of control group rats, HMFS-fed rats had significantly increased contents of six hepatic primary BAs (CDCA, αMCA, βMCA, TCDCA, TαMCA and TβMCA), four ileal primary BAs (UDCA, TCA, TCDCA and TUDCA) and three secondary BAs (DCA, LCA and ωMCA), especially for the HMFS with the highestsn-2 palmitic acid TAGs of 57.9% and OPL to OPO ratio of 1.4. Meanwhile, the inhibition of ileal FXR-FGF15 and activation of TGR5-GLP-1 signaling pathways in HMFS-fed rats were accompanied by the increased levels of enzymes involved in BA synthesis (CYP7A1, CYP27A1 and CYP7B1) in the liver and two key thermogenic proteins (PGC1α and UCP1) in perirenal adipose tissue, respectively. Moreover, increasingsn-2 palmitic TAGs and OPL to OPO ratio in HMFS also altered the microbiota composition both on the phylum and genus level in rats, predominantly microbes associated with bile-salt hydrolase activity, short-chain fatty acid production and reduced obesity risk, which suggested a beneficial effect on host microbial ecosystem. These observations provided important nutritional evidence for developing new HMFS products for infants.Keywords:sn-2 palmitic triacylglycerols;human milk fat substitute;BA metabolism;FXR;TGR5;gut microbiota
研究领域:
营养学
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微生物学
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代谢学
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分子生物学
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PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2022
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IF 10.723
Tao Wang,Junjie Han,Huanqin Dai,Jingzu Sun,Jinwei Ren,Wenzhao Wang,Shanshan Qiao,Chang Liu,Li Sun,Shuangjiang Liu,Dianpeng Li,Shenglong Wei,Hongwei Liu
Polysaccharides are known to confer protection against obesity via modulation of gut microbiota . To expand our knowledge of mushroom-derived prebiotics , we investigated the structural characteristics and anti-obesity effects of Lyophyllum decastes polysaccharides. Two heteroglycans were purified and characterized. The isolated polysaccharides effectively reduced obesity and the related disorders in the diet-induced obese (DIO) mice. An altered gut microbiota with enrichments of Bacteroides intestinalis and Lactobacillus johnsonii and an increase of secondary bile acids were detected in the polysaccharide-treated mice. Supplementation of B. intestinalis and L. johnsonii prevented the obesity and hyperlipidemia in DIO mice, demonstrating their causal linkage to the efficacy of polysaccharides. An enhancement of energy expenditure in the brown adipose tissues due to up-regulation of the secondary bile acids-activated TGR5 pathway was deduced to be one of the mechanisms underlying the effect of polysaccharides. These results confirmed Lyophyllum decastes -derived polysaccharides as new prebiotics for preventing and treating obesity.
研究领域:
营养学
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微生物学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Food Frontiers
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2025
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IF 6.9
Xiaole Zhao,Bing Zheng,Tianxiang Ao,Jianhua Xie,Yi Chen,Hesham El-Seedi,Hairong Huang,Baoting Liu,Qiang Yu
Polygonatum cyrtonema polysaccharide (PCP-80%) is one of the major active ingredients in Polygonatum cyrtonema . By establishing the type 2 diabetes mellitus (T2DM) rat model and applying multi-omics analysis, the present study aimed to explore the potential mechanism of PCP-80% to alleviate T2DM in terms of the interactions between intestinal microbiota and their metabolites. The results suggested that PCP-80% effectively improve the blood glucose and lipids levels, enhance intestinal barrier function. In addition, PCP-80% restored gut microbiota disorders, increased the secretion of short-chain fatty acids (SCFAs), and enhanced bile acid (BA)-converting enzyme-rich microbiota abundance. Furthermore, PCP-80% intervention significantly ameliorated BA dysmetabolism while enhancing metabolic homeostasis in T2DM rats. These changes activated the G protein-coupled bile acid receptor 1 (TGR5) and farnesoid X receptor (FXR), triggering fibroblast growth factor 15 (FGF15) secretion to ameliorate T2DM-induced intestinal barrier dysfunction and glucose/lipid dysregulation. Mechanistically, PCP-80% exerted therapeutic effects through a microbiota-bile acid crosstalk axis, wherein gut microbiota remodeling enhanced bile acid metabolism and amplified TGR5/FXR-FGF15 signaling, ultimately restoring metabolic homeostasis in T2DM rats.
研究领域:
药理学
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微生物学
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内分泌学
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代谢组学
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糖尿病研究
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胃肠病学
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高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2023
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IF 7.5
Xiongjie Sun,Yu Zhang,Gang Cheng,Tianxiang Zhu,Zhigang Zhang,Lei Xiong,Haiming Hu,Hongtao Liu
Ulcerative colitis (UC) has been confirmed as a disease with a high incidence and low cure rate worldwide. In severe cases, UC can develop into colon cancer. Modern research has confirmed that berberine (BBR) can treat UC by inhibiting the expressions of inflammatory factors. However, the contribution of gut microbiota and flora metabolites in treating UC with BBR remains unclear. In this study, the ameliorative effects of BBR on gut microbiota dysbiosis and flora metabolites were investigated in a dextran sodium sulfate (DSS)-induced UC rodent model. We found that BBR significantly improved the pathological phenotype, attenuated intestinal barrier disruption, and mitigated colonic inflammation in DSS mice. By 16 S rDNA sequencing, BBR alleviated gut microbiota dysbiosis in UC mice. Moreover, the gut microbiota depletion experiment confirmed that the therapeutic effect of BBR was inextricably correlated with the gut microbiota. Besides, the flora metabolites ( e.g. , short-chain fatty acids, bile acids, and 5-hydroxytryptamine) were studied using HPLC-MS. The results suggested that BBR ameliorated the bile acid imbalance induced by DSS in the liver and gut. Furthermore, BBR treatment repaired gut barrier damage. The above results revealed that BBR alleviated DSS-induced UC in mice by restoring the disturbed gut microbiota, elevating unconjugated and secondary bile acids in the gastrointestinal tract, and activating the FXR and TGR5 signal pathway. This study provides novel insights into the mechanism of BBR in treating UC.
研究领域:
药理学
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胃肠病学
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微生物学
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代谢组学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
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2024
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IF 6.7
Xue Bai,Jianjun Deng,Zhiguang Duan,Rongzhan Fu,Chenhui Zhu,Daidi Fan
Background Gastrointestinal mucositis stands as one of the most severe side effects of irinotecan (CPT-11). however, only palliative treatment is available at present. Therefore, there is an urgent need for adjunctive medications to alleviate the side effects of CPT-11. Purpose In this study, our objective was to explore whether ginsenoside Rh4 could serve as a modulator of the gut microbiota and an adjunctive agent for chemotherapy, thereby alleviating the side effects of CPT-11 and augmenting its anti-tumor efficacy. Study design A CPT-11-induced gastrointestinal mucositis model was used to investigate whether ginsenoside Rh4 alleviated CPT-11-induced gastrointestinal mucositis and enhanced the anti-tumor activity of CPT-11. Methods In this study, we utilized CT26 cells to establish a xenograft tumor model, employing transcriptomics, genomics, and metabolomics techniques to investigate the impact of ginsenoside Rh4 on CPT-11-induced gastrointestinal mucositis and the effect on the anti-tumor activity of CPT-11. Furthermore, we explored the pivotal role of gut microbiota and their metabolites through fecal microbiota transplantation (FMT) experiments and supplementation of the key differential metabolite, hyodeoxycholic acid (HDCA). Results The results showed that ginsenoside Rh4 repaired the impairment of intestinal barrier function and restored intestinal mucosal homeostasis in a gut microbiota-dependent manner. Ginsenoside Rh4 treatment modulated gut microbiota diversity and upregulated the abundance of beneficial bacteria, especially Lactobacillus_reuteri and Akkermansia_muciniphila , which further regulated bile acid biosynthesis, significantly promoted the production of the beneficial secondary bile acid hyodeoxycholic acid (HDCA), thereby alleviating CPT-11-induced gut microbiota dysbiosis. Subsequently, ginsenoside Rh4 further alleviated gastrointestinal mucositis through the TGR5-TLR4-NF-κB signaling pathway. On the other hand, ginsenoside Rh4 combination therapy could further reduce the weight and volume of colon tumors, promote tumor cell apoptosis, and enhance the anti-tumor activity of CPT-11 by inhibiting the PI3K-Akt signaling pathway, thus exerting a synergistic anti-tumor effect. Conclusion In summary, our findings confirm that ginsenoside Rh4 can alleviate CPT-11-induced gastrointestinal mucositis and enhance the anti-tumor activity of CPT-11 by modulating gut microbiota and its related metabolites. Our study validates the potential of ginsenoside Rh4 as a modulator of the gut microbiota and an adjunctive agent for chemotherapy, offering new therapeutic strategies for addressing chemotherapy side effects and improving chemotherapy efficacy.
研究领域:
肿瘤学
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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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PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2021
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IF 5.279
Ruiqian Duan,Xiao Guan,Kai Huang,Yu Zhang,Sen Li,Ji’an Xia,Meng Shen
A high-fat diet (HFD) causes hyperlipidemia, which worsens disturbances in bile acid (BA) metabolism and gut microbiota. This study aimed to investigate the regulation of flavonoids from whole-grain oat (FO) on BA metabolism and gut microbiota in HFD-induced hyperlipidemic mice. The experiment results showed that FO improved serum lipid profiles and decreased body weight and lipid deposition in HFD-fed mice. Through real-time qualitative polymerase chain reaction (RT-qPCR) and Western blot assays, by up-regulating the expression of PPARα, CPT-1, CYP7A1, FXR, TGR5, NTCP, and BSTP, and down-regulating those of SREBP-1c, FAS, and ASBT, FO suppressed lipogenesis, promoted lipolysis and BA synthesis, and efflux to faeces via the FXR pathway. 16s rRNA sequencing revealed that FO significantly increased Akkermansia and significantly decreased Lachnoclostridium, Blautia, Colidextribacter, and Desulfovibrio. Spearman’s correlation analysis showed that these bacteria were strongly correlated with hyperlipidemia-related parameters. Therefore, our results indicated that FO possessed an antihyperlipidemic effect via regulating the gut–liver axis, i.e., BA metabolism and gut microbiota.
研究领域:
营养学
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生物化学
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微生物学
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分子生物学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2022
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IF 5.988
Chuyao Liao,Di Wang,Siyuan Qin,Ying Zhang,Jie Chen,Ruijie Xu,Fengguo Xu,Pei Zhang
Irinotecan (CPT-11) in combination with 5-fluorouracil and leucovorin is a first-line chemotherapy regimen for the treatment of colorectal cancer; however, its clinical application is limited by the dose-limiting gastrointestinal toxicity of colitis. In our previous studies, several bile acids (BAs) were found significantly elevated in the colon of the CPT-11-induced rat colitis model. On the other hand, NLRP3 inflammasome has been reported to play important roles in mediating colitis. Interestingly, BA was stated to activate the NLRP3 inflammasome in some studies, while in some other reports, it showed an inhibitory effect. We assumed that the inflammatory status in different circumstances might have contributed to the controversial findings. In this study, we first discovered, under non-inflammatory conditions, that supplementing BA could activate the NLRP3 inflammasome in THP-1-differentiated macrophages and promote inflammation. In lipopolysaccharide (LPS)-induced inflammatory macrophages, however, BA inhibited the NLRP3 inflammasome and reduced inflammation. Further experiments demonstrated that Takeda G protein-coupled receptor 5 (TGR5) is essential in mediating the inhibitory effect of BA, while phospho-SP1 (p-SP1) is key to the activation. Furthermore, we applied the above findings to ameliorate CPT-11-caused colitis in rats by inhibiting SP1 with mithramycin A (MitA) or activating TGR5 using oleanolic acid (OA). Our findings may shed light on the discovery of effective interventions for reducing dose-limiting chemotherapy-induced colitis.
研究领域:
肿瘤学
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胃肠病学
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
Gut Microbes
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2024
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IF 12.2
Xiaoqiang Zhu,Xiaojuan Dai,Lijun Zhao,Jing Li,Yanhong Zhu,Wenjuan He,Xinlei Guan,Tao Wu,Li Liu,Hongping Song,Liang Lei
Abdominal obesity-related metabolic syndrome (MetS) has emerged as a significant global public health issue that affects human health. Flavonoids, such as quercetin, have been reported to exert obvious anti-obesity and lipid-lowering effects in both humans and animal models. However, the precise underlying mechanism remains elusive. In this study, we investigated the potential roles of gut microbiota-bile acids (BAs) interactions in quercetin-induced anti-obesity effects and metabolic benefits. Oral administration of quercetin significantly enhanced energy metabolism through activating thermogenesis of brown adipose tissues (BAT) and browning of white adipose tissues (WAT), thus mitigating metabolic dysfunctions in an abdominal obesity-related MetS mouse model. Further mechanistic studies demonstrated that quercetin treatment substantially promoted the generation of non-12α-hydroxylated BAs (non-12OH BAs), particularly ursodeoxycholic acid (UDCA) and lithocholic acid (LCA), in serum via regulating the overall structure of gut microbiota and enriching Lactobacillus. High level of non-12OH BAs bind to Takeda G protein-coupled receptor 5 (TGR5) on adipocytes to stimulate thermogenesis. Remarkably, fecal microbiota transplantation (FMT) from quercetin-treated mice replicated the effects of quercetin on non-12OH BAs generation and energy expenditure, which suggested gut microbiota reshape and concomitant BAs regulation were responsible for the benefits on energy metabolism of quercetin in the MetS mouse model. Our findings not only highlighted the critical role of gut microbiota-BAs crosstalk in mediating quercetin-induced energy expenditure, but also enriched the pharmacological mechanisms of quercetin in ameliorating MetS-related diseases.
研究领域:
药理学
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代谢学
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微生物学
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内分泌学
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PubMed
高影响因子
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