Cell Host & Microbe
·
2024
·
IF 20.6
Ying-Xi Xu,Lu-Di Liu,Jiang-Yuan Zhu,Shan-Shan Zhu,Bing-Qi Ye,Jia-Lu Yang,Jing-Yi Huang,Zhi-Hao Huang,Yi You,Wen-Kang Li,Jia-Lin He,Min Xia,Yan Liu
Hyperuricemia induces inflammatory arthritis and accelerates the progression of renal and cardiovascular diseases. Gut microbiota has been linked to the development of hyperuricemia through unclear mechanisms. Here, we show that the abundance and centrality of Alistipes indistinctus are depleted in subjects with hyperuricemia. Integrative metagenomic and metabolomic analysis identified hippuric acid as the key microbial effector that mediates the uric-acid-lowering effect of A. indistinctus. Mechanistically, A. indistinctus-derived hippuric acid enhances the binding of peroxisome-proliferator-activated receptor γ (PPARγ) to the promoter of ATP-binding cassette subfamily G member 2 (ABCG2), which in turn boosts intestinal urate excretion. To facilitate this enhanced excretion, hippuric acid also promotes ABCG2 localization to the brush border membranes in a PDZ-domain-containing 1 (PDZK1)-dependent manner. These findings indicate that A. indistinctus and hippuric acid promote intestinal urate excretion and offer insights into microbiota-host crosstalk in the maintenance of uric acid homeostasis.
研究领域:
微生物学
·
代谢组学
·
药理学
·
胃肠病学
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产品关联
DOI
PubMed
高影响因子
iMeta
·
2024
·
IF 23.7
Shi Zhong,Yu-Qing Sun,Jin-Xi Huo,Wen-Yi Xu,Ya-Nan Yang,Jun-Bo Yang,Wei-Jie Wu,Yong-Xin Liu,Chong-Ming Wu,You-Gui Li
Inflammatory bowel disease (IBD) is a significant global health concern. The gut microbiota plays an essential role in the onset and development of IBD. Sanghuangporus (SH), a traditional Chinese medicinal mushroom, has excellent anti-inflammatory effects and is effective at modulating the gut microbiota. Despite these attributes, the specific anticolitic effects of SH and the mechanisms through which the gut microbiota mediates its benefits remain unclear. Herein, we demonstrated that polyphenol-rich extract from SH effectively alleviated the pathological symptoms of dextran sodium sulfate (DSS)-induced colitis in mice by modulating the gut microbiota. Treatment with SH distinctly enriched Alistipes , especially Alistipes onderdonkii , and its metabolite 5-hydroxyindole-3-acetic acid (5HIAA). Oral gavage of live A. onderdonkii or 5HIAA potently mitigated DSS-induced colitis in mice. Moreover, both 5HIAA and SH significantly activated the aromatic hydrocarbon receptor (AhR), and the administration of an AhR antagonist abrogated their protective effects against colitis. These results underscore the potent efficacy of SH in diminishing DSS-induced colitis through the promotion of A. onderdonkii and 5HIAA, ultimately activating AhR signaling. This study unveils potential avenues for developing therapeutic strategies for colitis based on the interplay between SH and the gut microbiota. Graphical Sanghuangporus is a medical mushroom with potent anticolitic effects. It modulates the gut microbiota and specifically enriches Alistipes onderdonkii , which can produce 5-hydroxyindole-3-acetic acid, thus activating the aryl hydrocarbon receptor pathway and ameliorating colitis. Highlights Sanghuangporus (SH) polyphenol extract potently alleviated symptoms of colon colitis in dextran sodium sulfate-induced colitis mice. The gut microbiota especially Alistipes onderdonkii mediates the anticolitic effect of SH. The SH-enriched microbial metabolite 5-hydroxyindole-3-acetic acid exhibited an anticolitic effect via the activation of the aryl hydrocarbon receptor. The “gut microbiota-metabolites-signaling pathway” provides an effective perspective for the study of complex Chinese medicine systems.
研究领域:
微生物学
·
免疫学
·
药理学
·
胃肠病学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Shan Li,Ronghua Guo,Xiang Gao,Yin Wang,Jiaxin Wen,Ting Zhao,Xiaofei Guo,Junhui Li,Shiguo Chen,Duo Li
Fucosylated chondroitin sulfate from Pearsonothuria graeffei (FCS- Pg ), a natural macromolecular polysaccharide, has been proven to prevent obesity, but its underlying molecular mechanism is still unclear. C57BL/6 J mice fed on high fat diet (HFD) were administered FCS- Pg lasting for ten weeks. The results demonstrated that FCS- Pg supplementation reduced body weight with dosage manner compared with HFD group. The expressions of intestinal lipid synthesis related proteins such as cluster of differentiation 36 (CD36) in FCS- Pg group were lower than those in the HFD group. Compared with the normal group, HFD caused gut microbiota disorder in the colon. FCS- Pg supplementation at high dosage restored the gut microbiota composition with higher abundance of Alistipes and Bacteroidetes and lower abundance of Colidextribacter , Bilophila and Firmicutes compared with HFD group. Moreover, FCS- Pg decreased the expression of proteins involved in triglyceride synthesis such as glycerol 3-phosphate dehydrogenase 1 (GPD1) and increased the expression of proteins involved in lipolysis and thermogenesis such as adipose triglyceride lipase (ATGL) and uncoupling protein 1 (UCP1) in the white adipose tissue (WAT) compared with HFD group. In conclusion, our study suggested that FCS- Pg significantly prevented obesity and improved WAT function in HFD-fed mice by regulating intestinal lipid metabolism and microflora composition.
研究领域:
营养学
·
分子生物学
·
微生物学
·
肥胖研究
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代谢学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Microbiology Spectrum
·
2024
·
IF 3.7
Yvhao Xie,Xinxin Li,Qingshi Meng,Jinjun Li,Xin Wang,Liying Zhu,Weiwei Wang,Xiaoqiong Li
Tryptophan (TRP) metabolites have been identified as potent biomarkers for complications of type 2 diabetes mellitus (T2DM). However, it remains unclear whether the therapeutic effect of metformin in T2DM is related to the modulation of TRP metabolic pathway. This study aims to investigate whether metformin affects TRP metabolism in T2DM mice through the gut microbiota. A liquid chromatography-tandem mass spectrometry method was established to determine 16 TRP metabolites in the serum, colon content, urine, and feces of T2DM mice, and the correlations between metabolites and the T2DM mice gut microbiota were performed. The method demonstrated acceptable linearity (R2 > 0.996), with the limit of quantification ranging from 0.29 to 69.444 nmol/L for 16 analytes, and the limit of detection ranging from 0.087 to 20.833 nmol/L. In T2DM mice, metformin treatment effectively restored levels of indole-3-lactic acid (ILA), indole-3-propionic acid (IPA), and the ILA/IPA ratio, along with several aryl hydrocarbon receptor ligands in the serum, with a notable impact in the colon but not in the urine. This restoration was accompanied by a shift in the relative abundance of Dubosiella, Turicibacter, RF39, Clostridia_UCG-014, and Alistipes. Spearman’s correlation analysis revealed positive correlations between Turicibacter and Alistipes with IPA and indole-3-acetic acid. Conversely, these genera displayed negative correlations with ILA and kynurenine. In addition, our study revealed the presence of endogenous indole pathway in germ-free mice, and the impact of metformin on endogenous TRP metabolism in T2DM mice cannot be disregarded. Further research is needed to investigate the regulation of TRP metabolism by metformin.
研究领域:
药理学
·
微生物学
·
代谢组学
·
糖尿病研究
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2020
·
IF 5.162
Ye Mi,Yao Xian Chin,Wan Xiu Cao,Yao Guang Chang,Phaik Eem Lim,Chang Hu Xue,Qing Juan Tang
Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, has gradually emerged as a public health challenge worldwide. Carrageenan is a popular food additive that has been in use for decades. However, controversy exists regarding to the safety of carrageenan due to its exacerbation of colitis in experimental models. In this study, we studied the effects of vehicle and host intestinal microflora on carrageenan inflammatory properties in C57BL/6 J mice. We found that in high-fat diet model, native carrageenan in drinking water increased the disease activity index (DAI), myeloperoxidase (MPO) activity and the mRNA expression of TLR4 in colon, whereas carrageenan-supplemented diet has no visible effects. However, no signs of colitis were observed under low-fat diet regardless of the mode of vehicle used. Moreover, we discovered that carrageenan-induced colitis in high-fat diet model was robustly correlated with changes in the composition of gut microbiota, specifically Alistipes finegoldii and Bacteroides acidifaciens . Hence, we propose that the inflammatory property of carrageenan is influenced greatly by its intake form via modification of host intestinal microecology.
研究领域:
胃肠病学
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微生物学
·
营养学
✓ 已验证
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Ke Cai,Xin-Yue Cao,Fan Chen,Yue Zhu,Dong-Dong Sun,Hai-Bo Cheng,Jin-Ao Duan,Shu-Lan SU
ABSTRACT Background Xianlian Jiedu Decoction (XLJDD) has been used for the treatment of colorectal cancer (CRC) for several decades because of the prominent efficacy of the prescription. Despite the clear clinical efficacy of XLJDD, the anti-CRC mechanism of action is still unclear. Purpose The inhibitory effect and mechanism of XLJDD on CRC were investigated in the azoxymethane/dextran sulfate sodium (AOM/DSS)-induced mice. Methods The AOM/DSS-induced mice model was adopted to evaluate the efficacy after administering the different doses of XLJDD. The therapeutic effects of XLJDD in treating AOM/DSS-induced CRC were investigated through histopathology, immunofluorescence and ELISA analysis methods. In addition, metabolomics profile and 16S rRNA analysis were used to explore the effective mechanisms of XLJDD on CRC. Results The results stated that the XLJDD reduced the number of tumor growth on the inner wall of the colon and the colorectal weight/length ratio, and suppressed the disease activity index (DAI) score, meanwhile XLJDD also increased body weight, colorectal length, and overall survival rate. The treatment of XLJDD also exhibited the ability to lower the level of inflammatory cytokines in serum and reduce the expression levels of β -catenin, COX-2, and iNOS protein in colorectal tissue. The findings suggested that XLJDD has anti-inflammatory properties and may provide relief for those suffering from inflammation-related conditions. Mechanistically, XLJDD improved gut microbiota dysbiosis and associated metabolic levels of short chain fatty acids (SCFAs), sphingolipid, and glycerophospholipid. This was achieved by reducing the abundance of Turicibacter, Clostridium_sensu_stricto_1 , and the levels of sphinganine, LPCs, and PCs. Additionally, XLJDD increased the abundance of Enterorhabdus and Alistipes probiotics, as well as the content of butyric acid and isovaleric acid. Conclusion The data presented in this article demonstrated that XLJDD can effectively inhibit the occurrence of colon inner wall tumors by reducing the level of inflammation and alleviating intestinal microbial flora imbalance and metabolic disorders. It provides a scientific basis for clinical prevention and treatment of CRC.
研究领域:
肿瘤学
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药理学
·
微生物学
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代谢组学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2024
·
IF 4.9
Yong Zhang,Cong Wang,Hedong Lang,Hongtao Yu,Min Zhou,Xin Rao,Qianyong Zhang,Long Yi,Jundong Zhu,Mantian Mi
Exhaustive exercise is known to induce muscle damage characterized by inflammation and oxidative stress. Although “regular” and “weekend warrior” exercise regimens have been shown to confer comparable health benefits in human studies, such as reduced risks of all-cause, cardiovascular disease (CVD), and cancer mortality, their differential impacts on muscle damage post-exhaustive exercise remain unclear. This study aimed to compare the effects of long-term, moderate-intensity (LTMI) and short-term, high-intensity (STHI) training modalities, matched for total exercise volume, on gut microbiota, short-chain fatty acids (SCFAs), and exhaustive exercise-induced muscle damage in mice, as well as to evaluate the correlation between these factors. LTMI is considered a regular exercise regimen, while STHI shares some similarities with the “weekend warrior” pattern, such as promoting exercise intensity and condensing training sessions into a short period. Our findings indicate that LTMI training significantly enhanced the abundance of SCFA-producing bacteria, including Akkermansia , Prevotellaceae_NK3B31_group , Odoribacter , Alistipes , and Lactobacillus , thereby increasing SCFA levels and attenuating muscle damage following exhaustive swimming. In contrast, STHI training increased the abundance of opportunistic pathogens such as Staphylococcus and Bilophila , without altering SCFA levels, and was associated with exacerbated muscle damage. Moreover, we observed a significant negative correlation between the abundance of SCFA-producing bacteria and SCFA levels with the expression of inflammatory cytokines in the muscle of mice post-exhaustive exercise. Conversely, the abundance of Staphylococcus and Bilophila showed a notable positive correlation with these cytokines. Additionally, the effects of LTMI and STHI on exhaustive exercise-induced muscle damage were transmissible to untrained mice via fecal microbiota transplantation, suggesting that gut microbiota changes induced by these training modalities may contribute to their contrasting impacts on muscle damage. These results underscore the significance of selecting an appropriate training modality prior to engaging in exhaustive exercise, with implications for athletic training and injury prevention.
研究领域:
运动生理学
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微生物学
·
肌肉生物学
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胃肠科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Antioxidants
·
2024
·Vol. 13
·期 11
·1291
·
IF 6
Xinyao Li,Hao Ling,Zengyang He,Zihui Yang,Tao Jiang,Peng Huang,Jianguo Zeng
The hybrid plant edible grass (Rumex patientiaL. ×Rumex tianschanicusA. LOS), a member of the Rumex genus, presents a novel food source with a protein content of approximately 30–40%. By incorporating non-traditional feed sources, such as edible grass leaf powder (EGLP), into broiler production, costs could be reduced. The experimental subjects of this study were Arbor Acres (AA) broilers. A total of 300 newly hatched broilers were randomly divided into to five groups, with each group consisting of six cages, housing 10 birds per cage. The control group was fed a basal diet composed of maize and soybean meal. In the experimental groups, varying percentages (3%, 6%, 9%, and 12%) of EGLP were substituted for the corn–soybean meal in the basal diet. In the diet, for days 1–21, the corn content was reduced from 1.90% to 8.20%, and the soybean meal content was lowered from 1.50% to 6.00%. Similarly, in the diet, for days 22–42, the corn content was decreased from 1.17% to 7.00%, while the soybean meal content was reduced by 1.50% to 6.00%. The experiment lasted 42 days and was divided into two phases: the brooding phase (days 1 to 21) and the finishing phase (days 22 to 42). The results show that substituting 3% and 6% EGLP for corn and soybean meal significantly increased the average daily gain (ADG) during the brooding period compared to the control group (p< 0.01). Additionally, the group with a 3% substitution rate exhibited a significant increase in the average daily feed intake (ADFI) during the brooding phase (p< 0.01). Throughout the 42-day experiment, substituting 3% and 6% of EGLP for maize and soybean meal did not significantly affect the overall growth performance of broilers (p> 0.05). However, a 6% supplementation notably reduced the feed conversion ratio (FCR) (p< 0.01). Both the 3% (EG3) EGLP and 6% (EG6) EGLP replacement meals significantly enhanced the antioxidant capacity of broiler chickens, as indicated by the increased levels of the total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) (p< 0.01). Additionally, broilers supplemented with 3–12% showed a marked increase in cecal short-chain fatty acids (SCFAs) compared to the control group (p< 0.01). The 3% EGLP replacement diet also significantly boosted the prevalence ofLactobacillusin the cecum (p< 0.01). Furthermore, after EGLP supplementation, there was a higher abundance of SCFA-metabolizing bacteria, particularlyAlistipesandChristensenellaceae_R-7, compared to pre-treatment (p< 0.05). The prevalence ofClostridiumwas significantly greater in the groups receiving 9% and 12% EGLP (p< 0.05), whileButyrivibriolevels were notably higher after supplementation with 12% EGLP (p< 0.05).
研究领域:
动物科学
·
营养学
·
微生物学
·
家禽科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2022
·Vol. 36
·期 6
·2463-2480
·
IF 6.388
Yun Wang,Yuanyuan Xu,Xiaowei Xu,Hong Wang,Dong Wang,Wenchao Yan,Jiaying Zhu,Haiping Hao,Guangji Wang,Lijuan Cao,Jun Zhang
The Ginkgo biloba leave extract (GbE) is widely applied in the prevention and treatment of atherosclerotic cardiovascular diseases in clinical practice. However, its mechanism of actions has not been totally elucidated. In this study, we confirmed the beneficial effects of GbE in alleviating hypercholesterolemia, inflammation and atherosclerosis in Ldlr −/− mice, which were fed 12 weeks of Western diet (WD). Moreover, 16S rRNA sequencing revealed that GbE treatment reshaped the WD-perturbed intestinal microbiota, particularly decreased the Firmicutes / Bacteroidetes ratio and elevated the abundance of Akkermansia , Alloprevotella , Alistipes , and Parabacteroides . Furthermore, GbE treatment downregulated the intestinal transcriptional levels of proinflammatory cytokines and enhanced the expression of tight junction proteins, exerting the roles of attenuating the intestinal inflammation as well as repairing the gut barrier. Meanwhile, the targeted metabolomic analysis displayed that GbE treatment significantly reversed the dysfunction of the microbial metabolic phenotypes, including promoting the production of short chain fatty acids, indole-3-acetate and secondary bile acids, which were correlated with the atherosclerotic plaque areas. Finally, we confirmed GbE-altered gut microbiota was sufficient to alleviate atherosclerosis by fecal microbiota transplantation. In summary, our findings provide important insights into the pharmacological mechanism underlying the antiatherogenic efficacy of GbE.
研究领域:
药理学
·
心血管疾病
·
微生物学
·
代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2024
·
IF 3.8
Qiaoling Zhao,Fei Yang,Qiuyan Pu,Rui Zhao,Su Jiang,Yunping Tang
The protective effects of docosahexaenoic acid-enriched phosphatidylserine (DHA-PS, 50 or 100 mg/kg) on bisphenol A (BPA)-induced intestinal damage were assessed. The biochemical indices, pathological examination, non-targeted metabolomics integrated with gut microbiota analysis, and immunofluorescence analysis were used to investigate the protective effects of DHA-PS and its underlying regulatory mechanism. The DHA-PS treatment improved the pathology of intestinal tract and increased the expression levels of Claudin-1, Occludin, and ZO-1. In addition, the DHA-PS treatment also notably decreased the levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, and increased the antioxidant enzymes activities. Moreover, DHA-PS treatment increased the relative abundances of Akkermansia, Alistipes, Butyricicoccus, Coriobacteriaceae_ UCG-002 , Enterorhabdus , and Lachnospiraceae_ UCG-006. DHA-PS treatment alleviated BPA-induced intestinal damage by regulating the kynurenine pathway of tryptophan, lipid, and arachidonic acid metabolisms. Overall, this study suggested that DHA-PS could alleviate BPA-induced intestinal damage by enhancing the intestinal barrier integrity, improving gut microbial composition and metabolites, and inhibiting the TLR4/NF-κB pathways.
研究领域:
营养学
·
药理学
·
微生物学
·
代谢组学
·
毒理学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）