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Aquaculture Reports · 2023 · IF 3.7

Effects of Clostridium butyricum and sodium butyrate on growth performance, immunity, and gut microbiota of mirror carp Cyprinus carpio fed with soybean meal based diet

Yi Du,Long Cheng,Jianhua Zhao,Clement R. de Cruz,Hong Xu,Liansheng Wang,Qiyou Xu

This study investigated the effects of Clostridium butyricum (CB) and sodium butyrate (SB) on the growth performance, intestinal immune, and gut microbiota of mirror carp ( Cyprinus carpio ) fed with a high level of soybean meal. Three hundred sixty healthy carp fingerlings (∼3.74 g) were divided into eight dietary treatments with four replicates and ten fish per replicate. Which include basal diet (Control group, C0); C0 supplemented with three levels of CB, 3 × 10 7 cfu/kg (C1), 3 × 10 8 cfu/kg (C2), 3 × 10 9 cfu/kg (C3); three levels of SB, 500 mg/kg (S1), 1000 mg/kg (S2), 2 000 mg/kg (S3); and 3 × 10 8 cfu/kg CB+ 1 000 mg/kg SB (CS), respectively. In 8-week trial, the survival rate of all groups was 100%. Compared with C0, the Weight Gain, Feed Conversion Ratio, Protein Efficiency Ratio were not significantly different in all groups ( P  > 0.05). Crude protein and ether extract contents were increased significantly ( P  < 0.05) when supplemented with different levels of CB and SB, and ash content increased significantly in the CB groups ( P  < 0.05). Serum globulin increased and glucose decreased significantly ( P  < 0.05) in the CB and SB groups. The intestinal T-SOD and glutathione activity in the foregut, midgut, and hindgut were increased ( P  < 0.05), and villus height of foregut and midgut were higher in the CB and SB ( P  < 0.05). Protease activities in the foregut and midgut were significantly increased ( P  < 0.05) in the C2, C3, S2, and S3. The lipase activity of the C2 and C3 in foregut, midgut, and hindgut; S2, S3, and CS in the foregut; S3 in midgut were significantly increased ( P  < 0.05). The gut microbiota was modulated at the phylum and genera level by CB and SB administration. In summary, our results indicated that CB and SB could promote the whole body CP and EE content, intestine immunity, digestive enzyme activity, and intestinal morphology, and modulated gut flora in carp.

CAS / MDL: 7440-36-0
研究领域: 水产养殖 · 营养学 · 微生物学 · 渔业科学
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JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY · 2017 ·Vol. 44 ·期 8 ·1245-1260 · IF 2.81

Insights from the complete genome sequence of Clostridium tyrobutyricum provide a platform for biotechnological and industrial applications

Wu Qian,Liu Tingting,Zhu Liying,Huang He,Jiang Ling

Genetic research enables the evolution of novel biochemical reactions for the production of valuable chemicals from environmentally-friendly raw materials. However, the choice of appropriate microorganisms to support these reactions, which must have strong robustness and be capable of a significant product output, is a major difficulty. In the present study, the complete genome of the Clostridium tyrobutyricum strain CCTCC W428, a hydrogen- and butyric acid-producing bacterium with increased oxidative tolerance was analyzed. A total length of 3,011,209 bp of the C. tyrobutyricum genome with a GC content of 31.04% was assembled, and 3038 genes were discovered. Furthermore, a comparative clustering of proteins from C. tyrobutyricum CCTCC W428, C. acetobutylicum ATCC 824, and C. butyricum KNU-L09 was conducted. The results of genomic analysis indicate that butyric acid is produced by CCTCC W428 from butyryl-CoA through acetate reassimilation via CoA transferase, instead of the well-established phosphotransbutyrylase-butyrate kinase pathway. In addition, we identified ten proteins putatively involved in hydrogen production and 21 proteins associated with CRISPR systems, together with 358 ORFs related to ABC transporters and transcriptional regulators. Enzymes, such as oxidoreductases, HNH endonucleases, and catalase, were also found in this species. The genome sequence illustrates that C. tyrobutyricum has several desirable traits, and is expected to be suitable as a platform for the high-level production of bulk chemicals as well as bioenergy.

研究领域: 微生物学 · 基因组学 · 生物技术 · 工业生物处理
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ACS Applied Materials & Interfaces · 2025 · IF 8.2

Microfluidic Fabrication of Hyaluronic Acid–Cysteine-Modified Chitosan Microspheres for CD44-Targeted Probiotic Delivery in Colitis Treatment

Fengzhi Qiao,Ya Luo,Peng Lei,Shaolei Wang,Zhi Duan,Hongchang Cui,Tongjie Liu,Huaxi Yi,Cristabelle De Souza,Guanhua Xuan,Xiangzhao Mao,Zhao Ma,Lanwei Zhang,Kai Lin

Probiotics play a crucial role in regulating intestinal immune homeostasis and supporting gut health; however, oral administration faces challenges such as nonspecific distribution and low efficacy. To achieve precise and efficient delivery, in this study, a targeted delivery system embedded probiotics to the colonic inflammatory site CD44 was constructed by covalently linking hyaluronic acid (HA) to cysteine-modified chitosan (CCH) using microfluidic technology. Two probiotic strains, Bifidobacterium bifidum FL-276.1 and Clostridium butyricum ATCC 19398, were encapsulated within the modified chitosan matrix to form probiotics@CCH microspheres (MSs), with an average diameter of approximately 276 μm. Based on the receptor–ligand binding mechanism of HA and CD44, combined with the intestinal mucosal adhesion properties conferred by cysteine-modified chitosan, the probiotics@CCH MSs exhibited a high capture rate for inflammatory Caco-2 cells and demonstrated prolonged retention and targeted localization in a DSS-induced colitis mouse model. Furthermore, probiotics@CCH MSs contributed to maintaining intestinal homeostasis by modulating gut microbiota composition, enhancing short-chain fatty acid production, and supporting the intestinal barrier integrity. The microfluidic-based delivery system facilitates the precise localization of probiotics within the intestine, providing a theoretical basis for enhancing probiotic applications in gut health management.

CAS / MDL: 7048-04-6
研究领域: 生物医学工程 · 药学 · 胃肠病学 · 微生物学 · 材料科学
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ACS Synthetic Biology · 2022 · IF 5.249

Functional and Structural Roles of the Dimer Interface in the Activity and Stability of Clostridium butyricum 1,3-Propanediol Oxidoreductase

Amreesh Parvez,Yuvaraj Ravikumar,Renu Bisht,Junhua Yun,Yang Wang,Sabapathy Poorna Chandrika,Hossain M. Zabed,Xianghui Qi

Biosynthesis of 1,3-propanediol (1,3-PD) by 1,3-propanediol oxidoreductase (PDOR) is often limited by the stability issues. To address this issue, the goal of the present study was to engineer the Clostridium butyricum PDOR dimeric interface. The interface exists between the chains and plays a role in the synthesis of 1,3-PD, which is hindered by the increased temperature and pH. Herein, we engineered PDOR by HotSpot Wizard 3.0 and molecular dynamics simulations, improving its thermal stability, pH tolerance, and catalytic properties with respect to the wild-type PDOR activity at 37 °C. Compared to the activity of the wild-type PDOR, the N298C mutant showed 0.5-fold greater activity at pH 8.0, while the P299E mutant showed significantly increased activity of over five fold at pH 4.0. Further structural comparisons between the wild-type and P299E mutant revealed that the extraordinary stability of the P299E mutant could be due to the formation of additional hydrogen bonds and salt bridges. The N298C mutant also exhibits thermal stability at a broad range of temperature at pH 8 with respect to wild-type PDOR and other mutants. The molecular dynamics simulations revealed that stability profiles of P299E mutants at pH 4.0 are attributed to identical root mean square deviation values and stable conformations in the motif region present in the dimer interface of the enzyme. These findings suggest that the dimer interface motifs are essential for the compactness and stability of the PDOR enzyme; therefore, engineering the PDOR using a structure-guided approach could aid in improving its activity and stability under various physiological conditions (pH and temperature).

研究领域: 生物化学 · 酶工程 · 分子生物学
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Food Bioscience · 2024 · IF 4.8

Microbiota responses to different brans are conserved within individuals and associated with processing parameters

Zhentao Yao,Ge Zhang,Xin Wang,Jinjun Li,Yuting Qi,Yuanrong Jiang,Jie Gu,Liying Zhu,Xianrong Xu,Xiaoqiong Li

Processing techniques have been shown to alter the nutritional composition of rice bran (RB) and wheat bran (WB), influencing their ability to modify microbiota, but a systematic comparison is currently lacking. This study aimed to comprehensively investigate the effects of various processing methods, including physical modifications (grinding, extrusion, and steam explosion), enzymolysis (amylase, hemicellulose, and xylanase), and their combinations, on the modification of gut microbiota by RB and WB. Processing methods significantly altered the nutrient components of RB and WB as well as their capacity for gas and SCFAs production during in vitro fermentation. The RB23 (amylase treatment), RB31 (extrusion and hemicellulose treatment), and RB33 (steam explosion and xylanase treatment) samples exhibited the highest production of total SCFAs and butyric acid during in vitro fermentation. Overall, the microbiota responses to brans were conserved within individuals and the processing methods explained 21.6% of the variance. Fermentation of RB23, RB31, and RB33 samples was observed to enhance the richness of gut microbiota, decrease the Firmicutes/Bacteroidetes ratio, and stimulate the growth of Butyricicoccus and Faecallbacterium, while inhibiting the growth of Bilophila , Fusobacterium , and Escherichia-shigella . These findings may provide valuable insights for the processing of RB and WB.

研究领域: 食品科学 · 微生物学 · 营养学 · 生物技术
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Acta Pharmaceutica Sinica B · 2024 · IF 14.7

Colon-specific controlled release of oral liposomes for enhanced chemo-immunotherapy against colorectal cancer

Mengya Niu,Yihan Pei,Tiantian Jin,Junxiu Li,Liming Bai,Cuixia Zheng,Qingling Song,Hongjuan Zhao,Yun Zhang,Lei Wang

A colon-specific drug delivery system has great potential for the oral administration of colorectal cancer. However, the uncontrollable in vivo fate of liposomes makes their effectiveness for colonic location, and intratumoral accumulation remains unsatisfactory. Here, an oral colon-specific drug delivery system (CBS-CS@Lipo/Oxp/MTZ) was constructed by covalently conjugating Clostridium butyricum spores (CBS) with drugs loaded chitosan (CS)-coated liposomes, where the model chemotherapy drug oxaliplatin (Oxp) and anti-anaerobic bacteria agent metronidazole (MTZ) were loaded. Following oral administration, CBS germinated into Clostridium butyricum (CB) and colonized in the colon. Combined with colonic specifically β -glucosidase responsive degrading of CS, dual colon-specific release of liposomes was achieved. And the accumulation of liposomes at the CRC site furtherly increased by 2.68-fold. Simultaneously, the released liposomes penetrated deep tumor tissue via the permeation enhancement effect of CS to kill localized intratumoral bacteria. Collaborating with blocking the translocation of intestinal pathogenic bacteria from lumen to tumor with the gut microbiota modulation of CB, the intratumoral pathogenic bacteria were eliminated fundamentally, blocking their recruitment to immunosuppressive cells. Furtherly, synchronized with lipopolysaccharide (LPS) released from MTZ-induced dead Fusobacterium nucleatum and the tumor-associated antigens produced by Oxp-caused immunogenic dead cells, they jointly enhanced tumor infiltration of CD8 + T cells and reactivated robust antitumor immunity.

研究领域: 药学 · 癌症研究 · 药物递送系统 · 免疫疗法
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2024 · IF 7.7

Modulating butyric acid-producing bacterial community abundance and structure in the intestine of immunocompromised mice with neutral polysaccharides extracted from Codonopsis pilosula

XinQian Rong,QingLong Shu

Codonopsis pilosula , an important medicinal and edible plant in traditional Chinese medicine, is used widely as a tonifying herb for various immunodeficiency diseases. A neutral polysaccharide (CPPs-D1N1) was purified from C. pilosula , composed of fructose and glucose in a molar ratio of 97.28:2.72, with an average molecular weight of 5.985 kDa. Structural analysis revealed a backbone composed of →1)-β-D-Fruf-(2 → units with some β-D-Fruf-(2 → linkages. In a murine immunosuppression model induced by cyclophosphamide injection, oral treatment with C. pilosula polysaccharide was administered, investigating changes in gut microbiota during therapy. The polysaccharide modulated serum immunoglobulins (Ig-G, Ig-M), cytokines (IL-2, IL-6, TNFα), and spleen and thymus indices in immunodeficient mice. Additionally, functional gene primer sequencing enrichment methods revealed alterations in abundance, diversity, and structure of butyrate-producing bacterial populations in the gut, with primary differential genera identified as Butyribacter , Rumanococcus , Dysosmobacter , and Ruseburia . This study provides in vivo evidence supporting the beneficial effects of C. pilosula polysaccharide oral therapy in improving gut microbiota, particularly butyrate-producing bacteria, during treatment of immunosuppressive diseases.

CAS / MDL: 50-18-0
研究领域: 免疫学 · 微生物学 · 药理学 · 中医药
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Materials Today · 2025 · IF 22

Harnessing microbial hydrogen for remodeling tumor microenvironment to potentiate collaborative chemo-immunotherapy

Shi-Man Zhang,Ran Meng,Hong Chen,Hao Zhou,Xin-Chen Deng,Yan-Tong Lin,Wei-Qin Yao,Wei-Hai Chen,Xian-Zheng Zhang

Chemo-immunotherapy is fundamentally limited by insufficient tumor specificity and immunosuppressive tumor microenvironment (TME). Here, an engineered probiotic CB@PPH is elaborately constructed to remodel tumor microenvironment for potentiating collaborative chemo-immunotherapy. Specifically, phenylboronic acid-modified hyaluronic acid-coated paclitaxel (PTX)-loaded PCN-224 (PPH) nanoparticles are covalently conjugated with Clostridium butyricum (CB) to develop CB@PPH. Due to tumor hypoxia-tropism, CB@PPH facilitates the precise intratumoral delivery of PPH, and in situ kills tumor cells by inhibiting the depolymerization of tubulin. Moreover, the enriched CB@PPH at tumor tissues could persistently produce abundant microbial H 2 . On the one hand, the generated intratumoral H 2 would induce severe mitochondrial destruction and disrupt redox homeostasis within tumor cells, collaboratively amplifying immunogenic cell death signaling. On the other hand, microbial H 2 acts as an immune modulatory agent, remodeling the immunosuppressive TME into a pro-immunogenic milieu that activate robust antitumor immune responses. In combination with αPD-1 therapy, the engineered CB@PPH significantly inhibits the growth of subcutaneous tumors, as well as effectively suppresses the progression of distant tumors with a tumor inhibition rate of 91.0 %. This work underscores the innovative potential of microbial H 2 -assited chemo-immunotherapy, presenting a paradigm for the development of cancer therapeutic strategies.

CAS / MDL: 13520-92-8
研究领域: 癌症治疗 · 生物工程 · 微生物学 · 免疫学 · 纳米医学
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Acta Biomaterialia · 2025 · IF 9.6

Orally-administrable supramolecular probiotic capsules enable cooperative colon-targeted inflammation inhibition for ameliorating ulcerative colitis

Ting Wang,Jie Chen,Chuandong Shu,Xinkun Shen,Yuanyuan Fu,Menghuan Li,Zhong Luo

Ulcerative colitis (UC) is a prevalent gastrointestinal disease characterized by the chronical and refractory inflammation of colorectal mucosa and walls, which severely impairs overall well-being of individuals. Probiotics has shown tremendous promise for UC therapy due to its multifaceted mucosal barrier restoration and immunomodulation capabilities. Nevertheless, the successful administration of probiotics remains a clinical obstacle. Herein, we report a multifunctional supramolecular probiotic capsule based on clinically-tested biopolymers for UC therapy, which not only allow colon-targeted probiotic delivery via oral route but also enable concurrent delivery of hemostatic and anti-inflammatory drugs. Specifically, Clostridium butyricum (CB) was first engineered with protective norepinephrine (NE) coating and then encapsulated by self-assembled gelatin-based nanocomplexes modified with balsalazide and matrix metalloproteinase 2/9 (MMP2-/9)-responsive fibronectin peptides. The released balsalazide and fibronectin could induce rapid hemostasis and anti-inflammation actions to alleviate inflammation damage of the UC-affected colons in the short term, while CB could restore gut microbiota homeostasis to remodel intestinal immunocomposition and repair mucosal barrier for reducing UC risk in the long term. Overall, this study provides a promising option for UC treatment with good efficacy and minimal invasiveness. Statement of significance This study reports a supramolecular probiotic capsule with nanointegrative hemostatic and anti-inflammatory capacities for ulcerative colitis (UC) therapy, which could be orally administrated and activated in the inflamed colorectal sites. The probiotic capsules enable immediate UC symptom relief while also accelerating mucosal repair and preventing UC relapse in the long-term, offering an approach for UC treatment in the clinic.

研究领域: 胃肠病学 · 药学 · 生物医学工程
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2023 · IF 6.1

Intracellular Polysaccharides of Aspergillus cristatus from Fuzhuan Brick Tea Leverage the Gut Microbiota and Repair the Intestinal Barrier to Ameliorate DSS-Induced Colitis in Mice

Zhiyong Xie,Ziqi Zeng,Guijie Chen,Wei Dong,Yujia Peng,Weiqi Xu,Yi Sun,Xiaoxiong Zeng,Zhonghua Liu

The intracellular polysaccharides of Aspergillus cristatus (IPSs) from Fuzhuan brick tea have been demonstrated to improve immune function linked to modulating the gut microbiota. Herein, to further investigate the efficacy of IPSs to maintain gut homeostasis, the protection of the purified fraction of IPSs (IPSs-2) on the mice with colitis induced by dextran sulfate sodium (DSS) and the underlying mechanisms were explored in this study. The results revealed that IPSs-2 alleviated the typical symptoms of colitis and suppressed the excessive inflammatory mediators, regulating the genes related to inflammatory responses in the colon at the mRNA level. Meanwhile, IPSs-2 treatment reinforced the intestinal barrier function by ameliorating the DSS-induced histological injury, facilitating the differentiation of goblet cells to enhance Mucin-2 generation, and enhancing the expression of tight junction proteins to alleviate colitis. In addition, IPSs protected against colitis by promoting the production of short-chain fatty acids (SCFAs), the activation of SCFAs receptors, and the leverage of the gut microbiota via the enrichment of Bacteroides, Parabacteroides, Faecalibacterium, Flavonifractor_plautii, and Butyricicoccus, linking with reducing inflammation and repairing intestinal barrier function. Overall, our research revealed the therapeutic potential of IPSs-2 as a prebiotic for attenuating inflammatory bowel disease and provided a rationale for future investigation.

研究领域: 免疫学 · 微生物学 · 药理学 · 胃肠病学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2023 · IF 8.2

Malus baccata (Linn.) Borkh polyphenols-loaded nanoparticles ameliorate intestinal health by modulating intestinal function and gut microbiota

Lu Wang,Zhen Li,Siying An,Huipeng Zhu,Xiaoyu Li,Dawei Gao

The aim of this study was to construct the nanoparticles based on Hohenbuehelia serotina polysaccharides and mucin for encapsulation of the polyphenols from Malus baccata (Linn.) Borkh (MBP-MC-HSP NPs), and investigate their effects on intestinal function and gut microbiota in mice. The results showed that MBP-MC-HSP NPs did not have any toxic and side effect by determining organ indexes and hematological parameters. The colonic index, colonic length as well as colonic histology were significantly improved by treatment of MBP-MC-HSP NPs. Moreover, MBP-MC-HSP NPs could increase the fecal moisture (84.71 %) and accelerate the intestinal peristalsis (77.87 %), thus reducing the defecation time (1.68 h) of mice at certain extent. Through production of acetic acid, propionic acid and n-butyric acid, MBP-MC-HSP NPs remarkably decreased the pH of colonic feces to maintain intestinal health. 16S rRNA sequencing analysis showed that MBP-MC-HSP NPs could improve the abundances of Lactobacillus , Butyicicoccus and Ruminococcus and suppress the richness of Prevotella , Bifidobacterium and Desulfovibrio , thereby optimizing the structure and composition of gut microbiota. Furthermore, the metabolic profiles of gut microbiota were influenced by MBP-MC-HSP NPs based on prediction of KEGG and COG databases. Overall, this study suggests that MBP-MC-HSP NPs can be developed and utilized as probiotics in the nutritional food field.

研究领域: 药理学 · 营养学 · 微生物学 · 食品科学
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Journal of Functional Foods · 2024 · IF 3.8

Integrative metabolomics and gut microbiota analyses reveal the protective effects of DHA-enriched phosphatidylserine on bisphenol A-induced intestinal damage

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.

CAS / MDL: 80-05-7
研究领域: 营养学 · 药理学 · 微生物学 · 代谢组学 · 毒理学
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