Communications Biology
·
2025
·Vol. 8
·期 1
·1-17
·
IF 5.1
Wang He,Kang Tianyang,Li Weiwei
Gestational diabetes during pregnancy is associated with an increased risk of developmental abnormalities in offspring, but the underlying mechanisms remain unclear. It is not known how maternal metabolism and gut microbes influence kidney development in the fetus. Here we show that gestational diabetes alters maternal gut microbiota and reduces the production of key fatty acids that normally support kidney development in offspring. We find that these changes impair a molecular pathway involving the receptor GPR43 , which promotes the growth and migration of kidney cells. In a mouse model, restoring short-chain fatty acids or transferring gut bacteria from healthy donors improves kidney development in offspring, while blocking GPR43 reverses this effect. This study reveals a previously unknown link between maternal gut metabolism and fetal kidney formation and may guide future strategies to prevent congenital kidney disorders in children born to mothers with gestational diabetes.
研究领域:
发育生物学
·
微生物学
·
代谢学
·
分子生物学
·
肾脏病学
·
妇产科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Physiology
·
2022
·
IF 4.755
Jiang Xuan,Zhang Ying,Zhang Huaxing,Zhang Xiaoguang,Yin Xiaopeng,Yuan Fang,Wang Sheng,Tian Yanming
The heart has high energy requirements, with an estimated 40%–60% of myocardial ATP production derived from the oxidation of fatty acids under physiological conditions. However, the effect of short-chain fatty acids on myocardial contraction remains controversial, warranting further research. The present study sought to investigate the effects and mechanisms of acetate, a short-chain fatty acid, on myocardial contraction in rat ventricular myocytes. Echocardiography and Langendorff heart perfusion were used to evaluate cardiac function. Cell shortening and calcium transient were measured in isolated cardiomyocytes. The patch-clamp method determined the action potential and L-type Ca2+ current in cardiomyocytes. Moreover, the expression of GPR43, a type of short-chain fatty acid receptors in cardiomyocytes was examined by immunofluorescent staining and Western blot. We demonstrated that acetate transiently reduced left ventricular developmental pressure in isolated Langendorff heart perfusion model, with no effect on stroke volume and cardiac output in vivo. In addition, acetate transiently and reversibly inhibited cardiomyocyte contraction and calcium transient. Acetate did not affect the action potential and L-type Ca2+ currents in cardiomyocytes. As a short-chain fatty acid receptor, GPR43 was expressed in rat cardiomyocytes. Furthermore, the GPR43 antagonist GLPG0974 prevented the acetate-induced inhibitory effect on myocardial contraction. We conclude that acetate transiently inhibits contraction via the short-chain fatty acid receptor GPR43 in cardiomyocytes.
研究领域:
心脏病学
·
药理学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
PHARMACOLOGICAL RESEARCH
·
2021
·
IF 7.658
Shengjie Huang,Shiping Hu,Shuang Liu,Bo Tang,Yaojiang Liu,Li Tang,Yuanyuan Lei,Li Zhong,Shiming Yang,Song He
Background Recent evidence suggests that neuropsychiatric stabilizers have a place in resolving gastrointestinal disorders . Lithium carbonate (LC) is one of the most commonly used drugs for bipolar disorder clinically. Here, we estimate the therapeutic function of LC against colitis and investigate the mechanism of intestinal flora and metabolism modulation. Methods A colitis model was constructed by continuously administering 2.5% dextran sodium sulfate (DSS) solution daily for 7 days. Analysis of gut microbiota was carried out by 16S rRNA gene high-throughput sequencing. Spectrum antibiotic cocktail (ABX) and faecal microbiota transplantation (FMT) were employed to evaluate the protective effect of intestinal flora . Colonic Treg cells and related immune responses were detected by flow cytometry. Results LC treatment significantly alleviated colon inflammation by regulating gut microbial diversity and altering flora composition. Notably, LC treatment upregulated short-chain fatty acid (SCFA)-producing bacteria, especially Akkermansia muciniphila ( A. muciniphila ), and transformed metabolite SCFA profiles. LC activated anti-inflammatory Treg cell responses in colonic lamina propria (LP) in a G-protein coupled receptor 43 (GPR43)-dependent mechanism. ABX, FMT and single bacteria gavage experiments were conducted to confirm the above mechanism. Conclusions As an intestinal microbiome and metabolite modulator, LC alleviates colon inflammation in a GPR43-dependent manner through activating Treg cell responses. Therefore, the therapeutic strategy of the microbiome-metabolite-immune axis, as observed in the A. muciniphila -SCFA-Treg cell axis in our study, might provide a new direction for the treatment of IBD .
研究领域:
免疫学
·
微生物学
·
药理学
✓ 已验证
DOI
高影响因子
Frontiers in Neurology
·
2022
·
IF 4.086
Liao Hongsen,Li Haojia,Bao Hongguang,Jiang Li,Du Jiayue,Guo Yaoyi,Si Yanna
Objective: This study aims to analyze the changes of fecal short chain fatty acids (SCFAs) content and gut microbiota composition in sepsis associated encephalopathy (SAE) mice, further evaluating the effect of SCFAs on cognitive function and the underlying mechanism in SAE mice.Methods: A total of 55 male adult C57BL/6 mice (2–3 months of age, 20–25 g) were divided into four groups randomly: sham group (n = 10), cecal ligation and puncture group (CLP group, n = 15), CLP+SCFAs group (n = 15), and CLP+SCFAs+GLPG0974 group (n = 15). Seven days after surgery, fecal samples were collected for microbiota composition and SCFA analysis from 6 mice in each group randomly. Behavioral test was applied to assess cognitive impairment at the same time. After that, mice were sacrificed and brain tissue was harvested for inflammatory cytokines analysis.Results: The levels of acetic acid (.57 ± 0.09 vs 2.00 ± 0.24, p < 0.001) and propionic acid (.32 ± 0.06 vs .66 ± 0.12, p = 0.002) were significantly decreased in the CLP group compared with the sham group. The administration of SCFAs significantly increased the levels of acetic acid (1.51 ± 0.12 vs. 0.57 ± 0.09, p < 0.001) and propionic acid (0.54 ± 0.03 vs. 0.32 ± 0.06, p = 0.033) in CLP+SCFAs group compared with CLP group. Relative abundance of SCFAs-producing bacteria, including Allobaculum (0.16 ± 0.14 vs. 15.21 ± 8.12, p = 0.037), Bacteroides (1.82 ± 0.38 vs. 15.21 ± 5.95, p = 0.002) and Bifidobacterium (0.16 ± 0.06 vs. 2.24 ± 0.48, p = 0.002), significantly decreased in the CLP group compared with the sham group. The behavioral tests suggested that cognitive function was impaired in SAE mice, which could be alleviated by SCFAs pretreatment. ELISA tests indicated that the levels of IL-1β, IL-6, and TNF-α were elevated in SAE mice and SCFAs could lower them. However, the GPR43 antagonist, GLPG0974, could reverse the cognitive protective effect and anti-neuroinflammation effect of SCFAs.Conclusion: Our study suggested that in SAE, the levels of acetate and propionate decreased significantly, accompanied by gut microbiota dysbiosis, particularly a decrease in SCFAs-producing bacteria. GPR43 was essential for the anti-neuroinflammation and cognitive protective effect of SCFAs in SAE.
研究领域:
神经科学
·
微生物学
·
免疫学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Cellular and Infection Microbiology
·
2025
·
IF 4.8
Jingxuan Yu,Zhenyu Liu,Yan Wang,Yu Zhou,Wei Liu,Tao Wang,Qiubo Xie,Hongzhe Tian,Yalong Xu,Min Wang,Fuhan Zhao,Lin Wang,Guan Zhang,Dongliang Chen,Lei Gao,Tiejun Pan
Introduction: Kidney ischemia–reperfusion injury (IRI) is a major cause of acute kidney injury (AKI), characterized by aggravated inflammation and apoptosis following reperfusion. This study aimed to investigate the protective effects and mechanisms of fecal microbiota transplantation (FMT) in a rat model of kidney IRI.Methods: Sprague–Dawley rats(SDRs) subjected to 45 minutes of bilateral renal ischemia followed by reperfusion were prophylactically treated with FMT derived from guinea pigs or supplemented with propionic acid. Renal function, histopathology, inflammatory markers, apoptosis, proliferation, and gut microbiota composition were systematically evaluated.Results: The results demonstrated that FMT attenuated kidney IRI by remodeling the gut microbiota to enhance propionic acid production, which subsequently modulated inflammation and apoptosis via GPR43 signaling.Conclusions: These findings provide novel insights into microbiota-targeted therapeutic strategies for kidney IRI and highlight propionic acid as a potential therapeutic agent.
研究领域:
肾脏病学
·
微生物组学
·
分子生物学
·
免疫学
·
转化医学
·
代谢物信号传导
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Yu-yan Gu,Xiao-bing Cui,Jing Jiang,Ya-xin Zhang,Meng-hua Liu,Sai-bo Cheng,Yu-ye Li,Lin-ling Liu,Rong-xin Liao,Peng Zhao,Wen Jin,Yu-hua Jia,Jing Wang,Feng-hua Zhou
Ethnopharmacological relevance Dingxin Recipe Ⅲ (DXR Ⅲ) is a traditional Chinese medicine compound used for hyperlipidemia treatment in clinical practice. However, its curative effects and pharmacological mechanisms in hyperlipidemia have not been clarified to date. Aim of the study Studies have demonstrated that gut barrier was strongly implicated in lipid deposition. Based on gut barrier and lipid metabolism, this study examined the effects and molecular mechanisms of DXR Ⅲ in hyperlipidemia. Materials and methods The bioactive compounds of DXR Ⅲ were detected by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry, and its effects were evaluated in high-fat diet-fed rats. Specifically, the serum levels of lipids and hepatic enzymes were measured using the appropriate kits; colon and liver sections were obtained for histological analyses; gut microbiota and metabolites were analyzed by 16S rDNA sequencing and liquid chromatography-MS/MS; and the expression of genes and proteins was determined by real-time quantitative polymerase chain reaction and western blotting and immunohistochemistry, respectively. The pharmacological mechanisms of DXR Ⅲ were further explored by fecal microbiota transplantation and short-chain fatty acid (SCFAs)-based interventions. Results DXR Ⅲ treatment significantly downregulated serum lipid levels, mitigated hepatocyte steatosis and improved lipid metabolism. Moreover, DXR Ⅲ improved the gut barrier, specifically by improving the physical barrier in the colon, causing part composition changes in the gut microbiota, and increasing the serum SCFAs level. DXR Ⅲ also upregulated the expression of colon GPR43/GPR109A. Fecal microbiota transplantation from rats treated with DXR Ⅲ downregulated part hyperlipidemia-related phenotypes, while the SCFAs intervention significantly improved most of the hyperlipidemia-related phenotypes and upregulated the expression of GPR43. Moreover, both DXR Ⅲ and SCFAs upregulated the expression of colon ABCA1. Conclusion DXR Ⅲ protects against hyperlipidemia by improving the gut barrier, particularly the SCFAs/GPR43 pathway.
研究领域:
药理学
·
胃肠病学
·
代谢组学
·
中医
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2025
·
IF 6.1
Yinan Zhang,Qilei Chen,Yaning Xu,Yanming Lv,Yini Wang,Xin-yu Shi,Jiaqi Liu,Jie Wen,Xueting Li,Baixiang Li
Atrazine (ATR), a widely used herbicide, is linked to dopaminergic neurotoxicity and persistent gut microbiota dysbiosis after early life exposure. However, whether the gut microbiota mediates ATR-induced loss of dopaminergic neurons remains unclear. Mice were exposed to ATR from juvenility (4 th week) until adulthood (12 th week), after which exposure ceased until the 20 th week. The role of gut microbiota was confirmed through fecal microbiota transplantation (FMT), which was classified into different groups based on the donor's ATR treatment status. 16S rRNA sequencing revealed that Akkermansia , which exhibited significant differences across FMT groups, is a classic short-chain fatty acid (SCFA)-producing bacteria. FMT recipients receiving ATR-donor microbiota exhibited reduced colonic G Protein-Coupled Receptor 43 (GPR43), serum Glucagon-like Peptide-1 (GLP-1), and substantia nigra Glucagon-like Peptide-1 receptor (GLP-1R)/Tyrosine hydroxylase (TH) levels. Soy isoflavones (SIF), selected for their dual prebiotic and neuroprotective effects, attenuated ATR-induced dopaminergic neurotoxicity by enriching SCFA-producing gut microbiota and the level of SCFAs, thereby activating the GPR43/GLP-1/GLP-1R axis and reducing neuronal loss. These findings demonstrate the critical role of gut microbiota in ATR-induced dopaminergic neurodegeneration, positioning SIF-mediated microbiota modulation as a promising therapeutic approach within the "food-medicine homology" framework.
研究领域:
神经毒理学
·
环境健康
·
微生物组研究
·
神经药理学
·
营养科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR IMMUNOLOGY
·
2023
·
IF 3.6
Zhijun Zhao,Yongqing Tong,Yuting Kang,Zhuoran Qiu,Qiujie Li,Chao Xu,Geng Wu,Wei Jia,Pengtao Wang
Cigarette smoke is recognized as a major trigger for individuals with chronic obstructive pulmonary disease (COPD), leading to an amplified inflammatory response. The onset and progression of COPD are affected by multiple environmental and genetic risk factors, such as inflammatory mechanisms, oxidative stress, and an imbalance between proteinase and antiprotease. As a result, conventional drug therapies often have limited effectiveness. This study aimed to investigate the anti-inflammatory effect of sodium butyrate (SB) in COPD and explore its molecular mechanism, thereby deepening our understanding of the potential application of SB in the treatment of COPD. In our study, we observed an increase in the mRNA and protein expressions of inflammatory factors interleukin-1beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), Matrix metallopeptidase 9 (MMP9) and MMP12 in both NR8383 cell and rat models of COPD. However, these expressions were significantly reduced after SB treatment. Meanwhile, SB treatment effectively decreased the phosphorylation levels of nuclear transcription factor-kappa B (NF-κB) p65, c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) and inhibited the nuclear translocation of these proteins in the COPD cells, leading to a reduction in the expression of various inflammatory cytokines. Additionally, SB also inhibited the expression level of the Nod-like receptor pyrin domain 3 (NLRP3) inflammasome, which consists of NLRP3, apoptosis-associated speck-like protein (ASC), and Caspase-1 in the cigeratte smoke extract (CSE)-stimulated cells. Our results showed that CSE down-regulated the mRNA levels of G-protein-coupled receptor 43 (GPR43) and GPR109A, while SB only up-regulated the expression of GPR43 and had no effect on GPR109A. Moreover, additional analysis demonstrated that the knockdown of GPR43 diminishes the anti-inflammatory effects of SB. It is evident that siRNA-mediated knockdown of GPR43 prevented the reduction in mRNA expression of IL-1β, IL-6, TNF-α, MMP9, and MMP12, as well as the expression of phosphorylated proteins NF-κB p65, JNK, and p38 MAPKs with SB treatment. These findings revealed a SB/GPR43 mediated pathway essential for attenuating pulmonary inflammatory responses in COPD, which may offer potential new treatments for COPD.
研究领域:
药理学
·
肺科学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PLoS One
·
2023
·Vol. 18
·期 4
·e0283105
·
IF 3.7
Guifang Yuan,Song Wen,Xuemei Zhong,Xiaotong Yang,Linrui Xie,Xiuli Wu,Xiaoyu Li
Technically, symptom of offspring asthma is also closely reliant on its maternal high-fiber diet as well as the intestinal microbiome. Fruits and vegetables are abundant in inulin, and this naturally soluble dietary fiber is endowed with a potential value on offspring asthma control through the maternal intake, but the mechanism now remains less studied. In this study, rats were given with inulin-included drinking water, whereas in normal group rats were allowed with normal water. Afterwards, we analyzed both the formations of the offspring intestinal microbiome ahead of asthma model establishment and of the maternal intestinal microbiome through high throughput sequence and the short-chain fatty acids (SCFAs) by metabolomic analysis. Subsequently, lung inflammation indexes were detected by Elisa, and the expression of short-chain fatty acid receptors (GPR41, GPR43) in the offspring of asthma models were evaluated through qPCR assay. Inulin intake resulted in altered maternal intestinal microbiome composition, with a significant increase in SCFAs-producing bacteria (mainly Bifidobacterium ), attenuating the asthmatic inflammatory response in the offspring. Meanwhile, inulin intake during pregnancy modulates the composition of the intestinal microbiome of the offspring, and this alteration appears before the onset of asthma, hence, there should be further studies onto the impacts of offspring’s intestinal microbiome on asthma procession.
研究领域:
免疫学
·
微生物学
·
营养学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2025
·
IF 8
Zhenting Zhang,Sixiu Zhong,Ruihua Zhang,Qibing Zeng,Pinggui Lei,Wenjin Qiu,Wang Chen,Daoping Wang,Xinjing Wei,Qun Huang,Ting Hu,Peng Luo
Skeletal fluorosis is closely associated with inflammation and metabolic disorders caused by excessive fluoride exposure. Rosa roxburghii Tratt juice (RRTJ), a natural dietary supplement, has been widely used to manage diseases associated with inflammatory damage and metabolic disorders. However, it is largely unknown if RRTJ can mitigate fluoride-induced bone metabolism disorders and the underlying mechanisms. In this study, we demonstrated that RRTJ supplementation significantly improved fluoride exposure-induced bone metabolism disorders, enhanced anti-inflammatory responses, increased short-chain fatty acid concentrations (SCFAs), strengthened the intestinal barrier, and markedly enriched beneficial bacteria, particularly Ligilactobacillus spp. Notably, we identified Rosa roxburghii Tratt polysaccharides (RRTP) as a key component of RRTJ that significantly promotes the growth of Ligilactobacillus murinus . Additionally, RRTJ effectively alleviated fluoride-induced lipid metabolism disorders. A mechanistic study revealed that RRTJ fortifies intestinal barrier function via activating intestinal G-protein-coupled receptor 43 (GPR43) and inhibiting NF-κB signaling pathways, leading to ameliorating bone metabolism disorders. These findings reveal the unique mechanism of RRTJ in balancing bone metabolism and provide new insights into the interaction between natural products and the gut microbiota, offering potential dietary strategies to mitigate fluorosis-induced bone metabolism disorders.
研究领域:
营养学
·
微生物学
·
药理学
·
毒理学
·
骨骼生物学
·
代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Chen Mingjun,Feng Yang,Luo Dan,Zhang Chen,Zhou Jing,Dai Hengheng,Lin Mingxiong,Tong ZhanQi
Purpose: Wuwei Kushen Changrong capsule (Composite Sophora Colon-soluble Capsule, CSCC) is a Chinese patent medicine developed to treat ulcerative colitis. Studies highlight CSCC potential efficacy for ulcerative colitis (UC) but unclear mechanism limits its widely treatment for patients. We aimed to investigate the anti-colitis efficacy of CSCC and explore the mechanism by which GPR43 inhibits the NLRP3/STAT3 signaling pathway, thereby mediating the protective effects of CSCC on the intestinal barrier.Methods: The protective effects of CSCC were evaluated in a murine ulcerative colitis model induced by 3% DSS. Assessments included body weight, Disease Activity Index (DAI) score, colon length, and histopathological score. Colon tissue, cell function, and immune-inflammatory status were evaluated using immunohistochemistry, immunofluorescence, ELISA, and real-time fluorescence quantitative PCR (RT-PCR). Protein expression levels of relevant pathways and receptors were measured using Western blot. All experiments were repeated.Results: CSCC protected mice from DSS-induced colitis by upregulating Gpr43, promoting the expression of ZO-1 and Occludin tight junction proteins. Mechanistically, CSCC inhibits the MEK4/JNK1/STAT3 activation pathway, consequently suppressing the STAT3/NLRP3/IL-1β pathway and inhibiting the production of inflammatory factors such as IL-17A.Conclusion: The mechanisms through which CSCC protects against DSS-induced colitis may include upregulating Gpr43, inhibiting the STAT3/NLRP3 pathway, and suppressing inflammation factors like IL-17A. These findings highlight the mechanisms underlying CSCC’s anti-colitis effects and suggest its potential as a therapeutic candidate for managing the progression of UC.
研究领域:
药理学
·
免疫学
·
胃肠病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2023
·
IF 5.2
Huan-Huan Chen,Qi-Jun Wu,Tie-Ning Zhang,Yu-Hong Zhao
Background The association between gut microbes and short-chain fatty acids (SCFAs) and therapeutic responses of patients with lung cancer (LC) receiving therapy remains unknown. Methods Fecal and serum samples were prospectively collected from patients with LC, classified as responders, if they presented durable clinical benefits, and non-responders, if not. The composition of gut microbes was analyzed using 16S ribosomal DNA sequencing. Serum SCFA concentrations were detected using gas chromatography. Cell proliferation, migration, invasion, cell cycle, and apoptosis assays were performed on isobutyric acid-treated A549 cells. Reverse transcription-quantitative PCR, Western blotting, immunocytochemistry, and immunofluorescence staining experiments have been performed to investigate the expression of associated genes or proteins. Results Non-responders harbored higher microbiome α-diversity but lower β-diversity compared with responders. Compared to the patients with low α-diversity, those with high α-diversity showed significantly shorter progression-free survival. Additionally, β-diversity has also been observed between these two groups. Specifically, Parasutterella, Clostridiaceae , and Prevotella_7 were more abundant among responders, whereas Bacteroides_stercoris and Christensenellaceae_R-7_group were more abundant in non-responders. The serum SCFA (especially acetate and isobutyrate) levels tended to be higher in responders. Isobutyric acid inhibited the proliferation, migration, and invasion of A549 cells by inducing apoptosis and G1/S arrest while upregulating the expression of GPR41, GPR43, and GPR5C and downregulating that of PAR1, and increasing the activity of histone acetyltransferases. Conclusion We revealed the influence of gut microbiota and SCFAs on the therapeutic responses in patients with LC and the anti-tumor effect of isobutyric acid, indicating their potential use as therapeutic targets.
研究领域:
肿瘤学
·
微生物学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）