JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Shanshan Zhang,Yonggan Sun,Xinyu Bian,Fangwei Liu,Shaoping Nie
Inflammatory bowel disease (IBD) is linked to gut microbiota dysbiosis, and modulating microbiota through diet is a promising IBD management strategy. Larch arabinogalactan (AG) is a natural polysaccharide with potential prebiotic effects; however, its regulatory effects on gut microbiota and the underlying anti-inflammatory mechanisms remain unclear. Here, we demonstrated that AG improves gut homeostasis in dextran sulfate sodium-induced colitis mice, with effects depend on the gut microbiota. Further analysis revealed that AG notably enriched the Bacteroides, particularly Bacteroides thetaiotaomicron. Specifically, B. thetaiotaomicron exhibited anti-inflammatory activity, producing propionate and upregulating colonic G-protein-coupled receptor 41 (GPR41) expression, effects also observed in AG-treated mice. Collectively, our findings reveal the targeted regulatory effects of AG on gut microbiota and demonstrate that the B. thetaiotaomicron-propionate-GPR41 axis contributes to the amelioration of colitis by AG. These results provide new scientific evidence for the application of AG in health foods and offer novel insights for microbiota-targeted nutritional intervention.
研究领域:
微生物学
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免疫学
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营养科学
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胃肠病学
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分子生物学
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Cell Chemical Biology
·
2026
·Vol. 33
·期 1
·102-116
·
IF 7.2
Yucheng Guo,Zhenlin Ouyang,Wenbo He,Qian Qin,Jiaxin Zhang,Ting Yu,Min Jiao,Peter M. Hwang,Fang Zheng,Serge Muyldermans,Yurong Wen
Enterotoxigenic Bacteroides fragilis (ETBF) promotes colonic inflammation by secreting metalloenzyme toxins (BFTs). Understanding BFT mechanisms and developing neutralization strategies is critical. Here, we have solved the structures of BFT-1 and BFT-2, revealing that residue 357 in the active site of the catalytic domain explains the diversity of function observed in BFT subtypes. We demonstrate that BFTs can directly cleave human epithelial-cadherin at extracellular domain 4, with BFT-2 possessing the highest activity. Using an alpaca antibody library, we identified a single-domain antibody, Nb2.43, targeting the BFTs. Nb2.43 can neutralize all three subtypes of BFT by directly binding the metalloenzyme catalytic zinc ion with its CDR3 antigen-binding loop. Furthermore, Nb2.43 blocks cleavage of E-cadherin by BFT and prevents the damage caused by ETBF in vitro and in a mouse colitis model. This work provides structural insights into BFT diversity and delivers a therapeutic nanobody against ETBF-mediated inflammation.
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PREPARATIVE BIOCHEMISTRY & BIOTECHNOLOGY
·
2020
·
IF 1.415
Cai-Yun Liu,Wen-Bin Su,Li-Bin Guo,Ye-Wang Zhang
Heparinase I (Hep I) specifically degrades heparin to oligosaccharide or unsaturated disaccharide and has been widely used in preparation of low molecular weight heparin (LMWH). In this work, a novel Hep I from Bacteroides eggerthii VPI T5-42B-1 was cloned and overexpressed in Escherichia coli BL21 (DE3). The enzyme has specific activity of 480 IU·mg−1 at the optimal temperature and pH of 30 °C and pH 7.5, and the Km and Vmax were 3.6 mg·mL−1 and 647.93 U·mg−1, respectively. The Hep I has good stability with t1/2 values of 350 and 60 min at 30 and 37 °C, respectively. And it showed a residual relative activity of 70.8% after 21 days incubation at 4 °C. Substrate docking study revealed that Lys99, Arg101, Gln241, Lys270, Asn275, and Lys292 were mainly involved in the substrate binding of Hep I. The shorter hydrogen bonds formed between heparin and these residues suggested the higher specific activity of BeHep I. And the minimum conformational entropy value of 756 J·K−1 provides an evidence for the improved stability of this enzyme. This Hep I could be of interest in the industrial preparation of LMWH for its high specific activity and good stability.
研究领域:
生物化学
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酶学
·
药学
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iMeta
·
2024
·
IF 23.7
Qixing Nie,Yonggan Sun,Wenbing Hu,Chunhua Chen,Qiongni Lin,Shaoping Nie
Bioactive dietary fiber has been proven to confer numerous health benefits against metabolic diseases based on the modification of gut microbiota. The metabolic protective effects of glucomannan have been previously reported in animal experiments and clinical trials. However, critical microbial signaling metabolites and the host targets associated with the metabolic benefits of glucomannan remain elusive. The results of this study revealed that glucomannan supplementation alleviated high-fat diet (HFD)-induced insulin resistance in mice and that its beneficial effects were dependent on the gut microbiota. Administration of glucomannan to mice promoted the growth of Bacteroides ovatus . Moreover, colonization with B. ovatus in HFD-fed mice resulted in a decrease in insulin resistance, accompanied by improved intestinal barrier integrity and reduced systemic inflammation. Furthermore, B. ovatus -derived indoleacetic acid (IAA) was established as a key bioactive metabolite that fortifies intestinal barrier function via activation of intestinal aryl hydrocarbon receptor (AhR), leading to an amelioration in insulin resistance. Thus, we conclude that glucomannan acts through the B. ovatus -IAA-intestinal AhR axis to relieve insulin resistance. Graphical Supplementation with glucomannan alleviates insulin resistance. Glucomannan promotes the growth of Bacteroides ovatus , accompanied by improved intestinal barrier integrity and reduced systemic inflammation. B. ovatus -derived indoleacetic acid is a key bioactive metabolite that fortifies intestinal barrier function via the activation of intestinal aryl hydrocarbon receptor. Highlights Supplementation with glucomannan alleviates insulin resistance. Glucomannan promotes the growth of Bacteroides ovatus , accompanied by improved intestinal barrier integrity and reduced systemic inflammation. B. ovatus -derived indoleacetic acid is a key bioactive metabolite that fortifies intestinal barrier function via the activation of intestinal aryl hydrocarbon receptor.
研究领域:
营养学
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微生物学
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代谢疾病研究
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Cell Systems
·
2026
·
IF 7.5
Yucan Hu,Qingmei Li,Yingying Li,Yu Zeng,Linggang Zheng,Juntao Shen,Xiang Gao,Guo-Ping Zhao,Wei Zhao,Lei Dai
Gut Bacteroides are abundant and critical to human health, yet most are genetically cumbersome, non-model microbes. A widely applicable editing tool for Bacteroides is essential for gut microbiome manipulation. Here, we develop STIB (ShCAST-based transient insertion system for Bacteroides ), an efficient genome-editing tool derived from CRISPR-associated transposases that enables rapid and site-specific insertions independent of homologous recombination. By fusing a nicking homing endonuclease to the transposase and an ATPase to Cas12k, we systematically optimize STIB to minimize plasmid cointegration and achieve >97% on-target insertion. STIB exhibits broad applicability across different genomic loci in diverse Bacteroides species, including non-model species. Finally, we apply STIB to achieve species- and site-specific editing of distinct Bacteroides species within a complex synthetic gut microbiota. Overall, STIB expands the toolbox for the functional investigation and engineering of the human microbiome. A record of this paper’s transparent peer review process is included in the supplemental information.
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Cell Host & Microbe
·
2026
·
IF 23.2
Junxia Zhang,Changyun Liu,Yupeng Wang,Yusi Chen,Haibao Shang,Wen Zheng,Li Jin,Peng Xie,Yingjia Li,Yahan Liu,Yunxiao Zhang,Yang Wang,Wei Zhao,Han Xiao,Guisong Wang,Xin Zhang,Xiaolei Yang,Erdan Dong,Yan Zhang
Ischemia/reperfusion (I/R) injury is a key driver in cardiomyocyte loss and cardiac dysfunction in ischemic heart disease. Here, we uncover a previously unrecognized gut microbiota-mediated mechanism that contributes to myocardial I/R injury. Using murine I/R models and fecal microbiota transplantation, we demonstrate that the gut microbiota mediates cardiac damage through selective enrichment of Bacteroides acidifaciens ( B. acidifaciens ) following I/R-induced intestinal hypoxia and elevated luminal lactate levels. B. acidifaciens produces dipeptidyl peptidase 4 (BaDPP4), which degrades cardioprotective peptides (e.g., glucagon-like peptide-1 [GLP-1]) in the plasma, amplifying myocardial injury. Pharmacological inhibition of BaDPP4 with daurisoline, a microbial DPP4-specific inhibitor, mitigates cardiac dysfunction. In acute myocardial infarction patients with I/R injury, B. acidifaciens abundance and BaDPP4 levels correlate with clinical markers of cardiac damage. Together, these findings reveal a gut-heart axis whereby microbial-derived DPP4 exacerbates cardiac I/R injury and highlight the hypoxia-lactate-BaDPP4 axis as a promising target for microbiota-based cardioprotection.
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Nature Microbiology
·
2026
·
IF 18.7
Zhang Yue,Zhao Ying,Zhang Lu,Xuan Baoqin,Wang Zhenyu,Yu Bin,Li Weixun,Huang Xiaowen,Zhou Yilu,Ning Lijun,Ding Jinmei,Jiang Yi,Hu Muni,Shao Yuqi,Li Lingxi,Gao Xiang,Chen Shengliang,Chen Haoyan,Wang Fei,Cui Zhe,Fang Jing-Yuan,Hong Jie
Gut dysmotility is a common long-term effect of enterotoxigenic Bacteroides fragilis (ETBF) colonization but the underlying mechanisms are not clear. Here, using mouse colonization models, we found that ETBF-secreted B. fragilis toxin (BFT) causes loss of colonic myenteric neurons, which are crucial regulators of intestinal motility. BFT induced apoptosis in these neurons through the NOD1–RIPK2–CASP9–CASP3 pathway, leading to gut dysmotility that persisted even after the clearance of ETBF. Analyses of human inflammatory bowel disease and colorectal cancer patient cohorts showed a positive correlation between ETBF and Fusobacterium nucleatum abundance. In mice, F. nucleatum -derived 2-hydroxybutyric acid enhanced BFT production in ETBF by alleviating RprY-mediated suppression and aggravated neurotoxicity and dysmotility. This enteric neuron loss and dysmotility enhanced susceptibility to dextran sulfate sodium-induced colitis in mice. Therapeutically, a Bifidobacterium -based probiotic attenuated neuron toxicity and improved intestinal motility. Our findings reveal bacterial interactions regulating intestinal function and a potential clinical therapeutic approach to preventing outcomes of ETBF colonization.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2026
·Vol. 74
·期 33
·26290-26302
·
IF 6.7
He Ying,Yu Ziyang,Li Qiqiong,Tao Ze,Xu Yushan,Xie Junhua,Nie Shaoping
Bacteroides thetaiotaomicron (Bt)
degrades dietary glycans via carbohydrate-active enzymes (CAZymes),
but their spatial distribution and functional coordination remain
unclear. In this study, we characterized the “labor division”
during glycan degradation across four bacterial fractions: cytoplasm,
outer membrane, extracellular vesicles, and supernatant. All fractions
displayed hydrolytic activity. Proteomic analysis identified abundant
glycoside hydrolases, mainly GH32 enzymes encoded by PUL22, and their
components varied greatly. Untargeted metabolomics identified 45 shared
differential metabolites (e.g., carbohydrates and short-chain fatty
acids), indicating distinct hydrolytic capacities among fractions.
Notably, cross-feeding experiments confirmed that Bt EVs-mediated
degradation can support the growth of recipient bacteria. Collectively,
our results reveal a synergistic multicomponent strategy for glycan
degradation in Bacteroides , offering new insights
into glycan utilization and laying a foundation for developing postbiotics
and functional microbial products.
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CARBOHYDRATE POLYMERS
·
2022
·
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
·
分子生物学
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Food Bioscience
·
2023
·
IF 5.2
Yang Wang,Sijia Qu,Menghan Chen,Yue Cui,Chenshan Shi,Xiaolu Pu,Wenhui Gao,Quanhong Li,Junhua Han,Aixia Zhang
The fascinating ingredient of buckwheat fermented by probiotics with functional superiorities was considered as a substitute for milk-based foods . In this work, buckwheat milk fermented by probiotic lactic acid bacteria (FBM) was prepared. The effects of FBM on body weight, gut microbiota and short chain fatty acids (SCFA) in mice were also discussed. Results showed that the acidity levels of FBM within 15 days were in the range of 70–100 °T, and total microbial counts were higher than 1 × 10 6 CFU/mL. FBM showed significant effect in controlling weight gain. Also, intestinal flora diversity in mice fed with FBM was improved. The abundance of Barnesiella , Ruminococcus , Bacteroides and Prevotella in FBM group was significantly increased. Meanwhile, the contents of six SCFA in the FBM group were significantly higher than the other two groups. These findings will provide referential information in revealing the probiotic functions and developing buckwheat-based products as dairy alternatives.
研究领域:
食品科学
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微生物学
·
营养学
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高影响因子
Nature Microbiology
·
2026
·
IF 18.7
Ye Meng,Liu Xinyu,Peng Zhengxiong,Li Shuaichao,Jia Xiaoyu,Yang Xiyuchen,Jiang Shan,Wang Feng,Yang Xiaobing,Yu Juping,Liu Wei,Gao Xiangdong
Engineered therapeutic microbes for intestinal inflammation must be capable of gut colonization, sensitive detection of disease-associated biomarkers and targeted delivery of therapeutic molecules. Examples of microbes displaying all three characteristics are limited. Here we engineered Bacteroides thetaiotaomicron , a human gut commensal bacterium with colonization ability, colonic tropism and innate anti-inflammatory properties, as a chassis to create programmable bacterial strains termed Btbots. We developed genetic circuits that were integrated into the bacterial chromosome to sense two intestinal inflammation biomarkers, deoxycholic acid (DCA) and nitric oxide (NO), and to enhance surface display and secretion of therapeutic molecules in response. Btbots with these biosensors were developed that either display trefoil factor-3 to facilitate mucosal repair or secrete interleukin-35 to suppress inflammation. These Btbots sensed DCA and NO biomarkers and released therapeutic agents, alleviating colitis and modulating the gut microenvironment and microbiota in mouse models. This work establishes a proof of concept for localized sensing and consequent therapeutic molecule release for gastrointestinal applications, whose clinical potential awaits further investigation.
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Probiotics and Antimicrobial Proteins
·
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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