Research
·
2025
·
IF 10.7
Ningning He,Mengjie Mu,Xiaofang Li,Qingyuan Hao,Kaiwei Chen,Xinnan Zhao,Yang Sun,Haoyu Wang,Zhinan Wu,Hewei Liang,Mengmeng Wang,Liang Xiao,Tao Yu,Zhi-Peng Wang,Jixing Peng,Yuanqiang Zou,Shangyong Li
Antibiotic cocktails (ABX) serve as potent therapeutic interventions for refractory ulcerative colitis (UC), yet invariably induce gut dysbiosis. This study demonstrates that pectin oligosaccharides synergistically enhance ABX efficacy by restoring gut microbiota balance and selectively enriched antibiotic-resistant Parabacteroides goldsteinii in a colitis mouse model. Our results further indicate that the gavage administration of P. goldsteinii AM58-2XD markedly alleviated colitis via enhancing the branched-chain amino acid metabolic pathway, particularly by facilitating valine metabolism. Notably, these anticolitis effects were partially attenuated in P. goldsteinii ΔilvE mutants, which are defective in valine-derived isobutyrate (IBN) biosynthesis. We further demonstrated that exogenous IBN supplementation effectively alleviated colitis symptoms in mice and enhanced gut barrier function via activation of the peroxisome proliferator-activated receptor γ (PPARγ) pathway. Conditional knockout of PPARγ in Caco-2 intestinal epithelial cells markedly abrogated the IBN-induced enhancement of tight junctions, thereby substantiating the critical role of the IBN-PPARγ pathway in metabolite-mediated mucosal repair. Collectively, we delineate a prebiotic/probiotic–metabolite axis wherein P. goldsteinii facilitates mucosal repair via IBN/PPARγ-dependent epithelial metabolic reprogramming. This insight redefines antibiotic-resistant commensals as precise biotherapeutics for microbiota restoration in refractory UC management.
研究领域:
微生物组学
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炎症性肠病
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代谢生物学
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黏膜免疫
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转化医学
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肠道微生态
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DOI
PubMed
高影响因子
Microbiome
·
2024
·Vol. 12
·期 1
·1-19
·
IF 13.8
Zhang Yujun,Gao Yan,Li Chen,Zhang Yong-An,Lu Yuanan,Ye Jing,Liu Xueqin
Background Spring viremia of carp virus (SVCV) infects a wide range of fish species and causes high mortality rates in aquaculture. This viral infection is characterized by seasonal outbreaks that are temperature-dependent. However, the specific mechanism behind temperature-dependent SVCV infectivity and pathogenicity remains unclear. Given the high sensitivity of the composition of intestinal microbiota to temperature changes, it would be interesting to investigate if the intestinal microbiota of fish could play a role in modulating the infectivity of SVCV at different temperatures. Results Our study found that significantly higher infectivity and pathogenicity of SVCV infection in zebrafish occurred at relatively lower temperature. Comparative analysis of the intestinal microbiota in zebrafish exposed to high- and low-temperature conditions revealed that temperature influenced the abundance and diversity of the intestinal microbiota in zebrafish. A significantly higher abundance of Parabacteroides distasonis and its metabolite secondary bile acid (deoxycholic acid, DCA) was detected in the intestine of zebrafish exposed to high temperature. Both colonization of Parabacteroides distasonis and feeding of DCA to zebrafish at low temperature significantly reduced the mortality caused by SVCV. An in vitro assay demonstrated that DCA could inhibit the assembly and release of SVCV. Notably, DCA also showed an inhibitory effect on the infectious hematopoietic necrosis virus, another Rhabdoviridae member known to be more infectious at low temperature. Conclusions This study provides evidence that temperature can be an important factor to influence the composition of intestinal microbiota in zebrafish, consequently impacting the infectivity and pathogenicity of SVCV. The findings highlight the enrichment of Parabacteroides distasonis and its derivative, DCA, in the intestines of zebrafish raised at high temperature, and they possess an important role in preventing the infection of SVCV and other Rhabdoviridae members in host fish.
Video Abstract
研究领域:
水产养殖
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微生物学
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病毒学
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鱼类健康
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DOI
PubMed
高影响因子
BMC MICROBIOLOGY
·
2024
·Vol. 24
·期 1
·1-15
·
IF 4
Wang Benlin,Qiu Yifeng,Xie Ming,Huang Pengcheng,Yu Yao,Sun Qi,Shangguan Wentai,Li Weijia,Zhu Zhangrui,Xue Jingwen,Feng Zhengyuan,Zhu Yuexuan,Yang Qishen,Wu Peng
Objective Bladder cancer(BCa) was a disease that seriously affects patients’ quality of life and prognosis. To address this issue, many researches suggested that the gut microbiota modulated tumor response to treatment; however, this had not been well-characterized in bladder cancer. In this study, our objective was to determine whether the diversity and composition of the gut microbiota or the density of specific bacterial genera influence the prognosis of patients with bladder cancer. Methods We collected fecal samples from a total of 50 bladder cancer patients and 22 matched non-cancer individuals for 16S rDNA sequencing to investigate the distribution of Parabacteroides in these two groups. Further we conducted follow-up with cancer patients to access the impact of different genera of microorganisms on patients survival. We conducted a Fecal Microbiota Transplantation (FMT) and mono-colonization experiment with Parabacteroides distasonis to explore its potential enhancement of the efficacy of anti-PD-1 immunotherapy in MB49 tumor-bearing mice. Immunohistochemistry, transcriptomics and molecular experiment analyses were employed to uncover the underlying mechanisms. Results The 16S rDNA showed that abundance of the genus Parabacteroides was elevated in the non-cancer control group compared to bladder cancer group. The results of tumor growth curves showed that a combination therapy of P. distasonis and ICIs treatment significantly delayed tumor growth and increased the intratumoral densities of both CD4 + T and CD8 + T cells. The results of transcriptome analysis demonstrated that the pathways associated with antitumoral immune response were remarkably upregulated in the P. distasonis gavage group. Conclusion P. distasonis delivery combined with α-PD-1 mAb could be a new strategy to enhance the effect of anti-PD-1 immunotherapy. This effect might be achieved by activating immune and antitumor related pathways.
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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分子生物学
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DOI
高影响因子
Cell Reports
·
2019
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IF 7.815
Kai Wang,Mingfang Liao,Nan Zhou,Li Bao,Ke Ma,Zhongyong Zheng,Yujing Wang,Chang Liu,Wenzhao Wang,Jun Wang,Shuang-Jiang Liu,Hongwei Liu
Summary We demonstrated the metabolic benefits of Parabacteroides distasonis (PD) on decreasing weight gain, hyperglycemia, and hepatic steatosis in ob/ob and high-fat diet (HFD)-fed mice. Treatment with live P. distasonis (LPD) dramatically altered the bile acid profile with elevated lithocholic acid (LCA) and ursodeoxycholic acid (UDCA) and increased the level of succinate in the gut. In vitro cultivation of PD demonstrated its capacity to transform bile acids and production of succinate. Succinate supplementation in the diet decreased hyperglycemia in ob/ob mice via the activation of intestinal gluconeogenesis (IGN). Gavage with a mixture of LCA and UDCA reduced hyperlipidemia by activating the FXR pathway and repairing gut barrier integrity. Co-treatment with succinate and LCA/UDCA mirrored the benefits of LPD. The binding target of succinate was identified as fructose-1,6-bisphosphatase, the rate-limiting enzyme in IGN. The succinate and secondary bile acids produced by P. distasonis played key roles in the modulation of host metabolism.
研究领域:
微生物学
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代谢学
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胃肠病学
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DOI
PubMed
高影响因子
BMC GASTROENTEROLOGY
·
2026
·
IF 3.2
Yao Jinwen,Gao Xia,Zhu Lin,Wang Linlin,Chen Qian,Liang Weijuan,Feng Huaili,You Ting,Wei Changli,Liu Yuqi,Zhang Hongyang,Chen Chengzhi,Chen Li
Background Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in childhood, with methylphenidate hydrochloride (MPH) as its first-line pharmacotherapy. Though effective, MPH is associated with underrecognized gastrointestinal adverse events warranting further investigation. Recently, the gut microbiota has attracted attention for treating gastrointestinal distress, but research on its role in alleviating MPH-induced gastrointestinal reactions remains scarce. Methods Herein, Wistar-Kyoto rats (WKY) served as controls alongside spontaneously hypertensive rats (SHR) to explore MPH-induced gastrointestinal adverse drug reactions. The gastrointestinal phenotypes, colonic histopathological characteristics, and inflammatory factor levels were evaluated, and the gut microbiota profiles were analyzed via 16S rRNA gene sequencing. The protective effect of Parabacteroides distasonis ( P. distasonis ) was further verified by supplementing the treated rats with this strain. Results We demonstrated MPH induced diarrhea and colonic inflammatory responses in rats. 16S rRNA gene amplicon sequencing revealed that MPH-treated rats had significantly decreased gut microbiota health index, increased dysbiosis index, and reduced P. distasonis abundance, suggesting MPH-induced gastrointestinal reactions may correlate closely with reduced P. distasonis . Further experiments confirmed that P. distasonis supplementation effectively alleviated diarrhea and colonic inflammatory responses in MPH-treated rats. Conclusions Collectively, this is the first study verifying that P. distasonis supplementation mitigates MPH-induced gastrointestinal adverse reactions, providing a novel intervention strategy to improve tolerance of ADHD pharmacotherapy.
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高影响因子
Advanced Science
·
2025
·
IF 14.1
Yimeng Chen,Shujun Jiang,Haolu Wang,Mengzhen Si,Haixia Wu,Xinyi Liang,Shenmeng Yao,Yanliang Zhang,Xiaodong Wen,Jie Yang
The gut bacterium Parabacteroides spp. is increasingly recognized for its therapeutic potential in treating metabolic disorders. However, the role of Parabacteroides johnsonii in metabolic disorders is never reported. Here, this study finds that the abundance of P. johnsonii in the feces is negatively correlated with the blood glucose and lipid levels of obese patients. Oral administration of live P. johnsonii improved the metabolic dysfunction in high fat diet (HFD)-fed mice, accompanied by the alleviation of leaky gut and the systemic inflammation. P. johnsonii enhanced the catabolism of branched-chain amino acids (BCAAs) to branched-chain short-chain fatty acids (BSCFAs) in gut. Particularly, the conversion of valine to isobutyrate is correlated to the symptoms of obese patients. Isobutyrate intervention mirrored the favorable effects of P. johnsonii on HFD-fed mice. Isobutyrate increased H3K14 acetylation at Fgf1b promoters and activated its transcription through inhibition of HDAC3 in colon, thereby maintaining the intestinal barrier integrity. The natural product stachyose exerted anti-obesity effects by enhancing the growth of P. johnsonii . These results offered insights into the mechanisms underlying the potential of P. johnsonii , isobutyrate, and stachyose in treating metabolic disorders. Graphical Clinical discovery and the proposed underlying mechanism by how P. johnsonii ameliorated metabolic disorders.
研究领域:
微生物学
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代谢紊乱
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肠道菌群
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营养学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Translational Medicine
·
2025
·Vol. 23
·期 1
·1363
·
IF 7.5
Li Mengyun,Zhang Xiaobing,Lu Jiafeng,Xiang Junjie,Wu Jie,Zheng Matao,Yang Siwei,He Lingyan,Shao Xian
Background Increasing evidence implicates the gut microbiota in the pathogenesis of Parkinson’s disease (PD). Microbiota-targeted interventions may be a promising therapeutic approach. Isoliquiritigenin (ISL), a natural flavonoid and primary pharmacological constituent of licorice (Glycyrrhiza), has neuroprotective effects. Whether this neuroprotection involves modulation of the gut microbiota is unclear. Purpose The study assessed whether ISL mediates neuroprotective in PD by modulating the gut microbiota, and investigated the functional involvement of Parabacteroides distasonis ( P. distasonis ) in this process. Methods Mice with chemically-induced PD were first treated with ISL via oral gavage to assess its therapeutic effects. To investigate the microbiota-mediated mechanisms, fecal microbiota transplantation (FMT) from ISL-treated donors and direct gavage of live or heat-killed P. distasonis were performed in separate cohorts. Behavioral performance, dopaminergic neuron integrity, intestinal barrier function, neuroinflammation, gut microbiota composition, and serum metabolomic profiles were systematically evaluated. Results ISL and FMT significantly improved motor deficits and protected dopaminergic neurons in the substantia nigra. ISL treatment compositionally reshaped the gut microbiota by suppressing pro-inflammatory genera and enriching beneficial bacteria, such as Parabacteroides . Oral administration of live P. distasonis fully reproduced the neuroprotective effects of ISL, including improved motor function, reduced neuroinflammation, restoration of blood–brain barrier integrity, and attenuation of intestinal mucosal damage. Heat-killed P. distasonis had no significant effects. Metabolomic analysis revealed that ISL and live P. distasonis jointly regulate neuroprotective pathways and metabolites related to the gut–brain axis. Conclusion ISL alleviates PD-related pathology partly through gut microbiota remodeling, with P. distasonis as a potential mediator.
研究领域:
神经科学
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微生物组研究
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药理学
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代谢组学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Jiaojiao Ding,Tiexiang Gao,Songlin Liu,Zhezhe Li,Baifei Hu,Junping Zhen,Xiaowei Yao,Hongtao Liu,Haiming Hu
Epimedin C, an anti-cardiovascular disease natural compound derived from Herba Epimedii , exhibits low oral bioavailability, with its metabolism closely related to the gut microbiota. In this study, we investigated the roles of intestinal bacteria in the catabolism of epimedin C. We discovered that a strain of Parabacteroides distasonis QZH 1201 ( P. distasonis ) from human fecal samples can convert epimedin C to 2”-O-rhamnosylicariside II and baohuoside I. More importantly, we identified an α-L-rhamnosidase enzyme from P. distasonis (PdRha), which plays a crucial role in this process by efficiently transforming epimedin C into icariside I. PdRha showed optimal activity at pH 6 and a temperature of 50 °C. Under the condition that the final concentration of epimedin C was 0.5 mM, its conversion efficiency reached 78.72 %. Additionally, we investigated the substrate profile of PdRha and discovered that it can hydrolyze rutin, naringin, and icariin, releasing isoquercitrin, prunin, and icariside I. Molecular docking was performed to gain insights into the enzymatic mechanism. This study provides valuable insights into how a common intestinal symbiotic bacterium processes an important natural flavonoid.
研究领域:
微生物学
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药理学
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生物化学
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DOI
PubMed
高影响因子
Probiotics and Antimicrobial Proteins
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2025
·
IF 4.4
Wu Yuehua,Liu Zhaoyi,Zhang Hongyang,Zhou Lixiao,Liang Weijuan,Su Peng,Zeng Zhijun,Zhao Feng,Qiu Jingfu,Chen Chengzhi
Obesity is a common health problem marked by the accumulation of excess body fat beyond the range characteristics of a healthy weight, affecting millions worldwide. Although advancements have been made in the realm of probiotic therapy for obesity, studies on the combined use of probiotics for the treatment of obesity have yet to be well explored. In this study, we investigated the potential of Parabacteroides goldsteinii ( P. goldsteinii ) and Bacteroides sartorii ( B. sartorii ) combinations and their microencapsulated forms for treating obesity. We identified different probiotic strains by 16S rRNA analysis in obese and healthy mice. The activity of these probiotics was evaluated in vitro under simulated gastrointestinal conditions. In vivo, the effects of probiotics on obese mice were assessed by monitoring body weight, glucose tolerance, colon integrity, and various molecular markers. Our results suggested that P. goldsteinii and B. sartorii were shown to be less abundant in obese mice ( P < 0.05). Compared with the control group mice, the obese phenotypes of the probiotics intervention group mice were significantly improved ( P < 0.05). Further results showed that compared with the control group mice, the expression of the FTO in the liver tissue of the probiotics intervention group mice was downregulated ( P < 0.05), while the expression of the Ampk gene was upregulated ( P < 0.05), indicating that probiotic intervention had reduced the expression of obesity-related genes in mice and had alleviated their obese condition. Furthermore, Microcapsule was remarkably effective in maintaining the viability of probiotics and facilitating their persistence, leading to a significant reduction in weight gain in mice compared with controls within just one week ( P < 0.05). Taken together, our study demonstrates that the intervention using the combination of P. goldsteinii and B. sartorii is more effective in treating obesity than using either probiotic alone. The encapsulation approach further enhances the anti-obesity efficacy of the combined probiotic mixture.
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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
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心血管疾病
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微生物学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL BIODETERIORATION & BIODEGRADATION
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2021
·
IF 4.32
Zhendong Wu,Yimin Pan,Fengmin Ma,Qiaoqiao Ren,Jiguo Wu,Yunxia Jiang,Yumei He,Yingxin Yu,Guoxia Zhang
The gut microbiome is crucial for the health of animals including human and is sensitive to environmental factors. Dechlorane Plus (DP) is a widely used polychlorinated flame retardant in commercial products for which general human population has been exposed to, but its effects on the gut microbiota are largely unknown. In this work, experiments were conducted to examine the effect of DP exposure on the intestinal microbiota by using Sprague-Dawley rats and a simulator of the human intestinal microbial ecosystem (SHIME). 16S rRNA gene high-throughput sequencing revealed that DP exposure in vivo reduced the relative abundance of the genera Prevotella , Quinella , and Ruminococcus , exposure in vitro decreased the relative abundance of Coriobacteriaceae , Parabacteroides , Bilophila , Sporolactobacillus , and Klebsiella . The phyla Synergistetes and Lentisphaerae were only detected in the descending colon . DP exposure also increased the concentrations of short-chain fatty acids (SCFAs) produced by the gut microbe both in vivo and in vitro, but SCFA metabolism was gradually inhibited as the increase of DP concentrations. These results indicated that DP exposure changed both the structure and metabolic function of the gut microbiota, suggesting more attention should be concentrated on the health effects of DP exposure, especially at higher doses.
研究领域:
环境科学
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微生物学
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毒理学
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分子生物学
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DOI
高影响因子
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