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Phage-mediated horizontal gene transfer and its implications for the human gut microbiome

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Gastroenterology Report 2022年第1期10卷 78-89页

作者： Tatiana Borodovich Andrey N.Shkoporov R.paul ross Colin Hill APC Microbiome Ireland University College CorkCorkIreland School of Microbiology University College CorkCorkIreland

Horizontal gene transfer(HGT)in the microbiome has profound consequences for human health and *** spread of antibiotic resistance genes,virulence,and pathogenicity determinants predominantly occurs by way of *** exists of extensive horizontal transfer in the human gut *** transduction is a type of HGT event in which a bacteriophage transfers non-viral DNA from one bacterial host cell to *** abundance of tailed bacteriophages in the human gut suggests that transduction could act as a significant mode of HGT in the gut *** we review in detail the known mechanisms of phage-mediated HGT,namely specialized and generalized transduction,lateral transduction,gene-transfer agents,and molecular piracy,as well as methods used to detect phage-mediated HGT,and discuss its potential implications for the human gut microbiome.

关键词： gut phageome horizontal gene transfer gene transduction phage-mediated gene transfer

Progress in pancreatic cancer therapeutics: The potential to exploit molecular targets

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World Journal of Pharmacology 2015年第2期4卷 180-192页

作者： Kiruthikah Thillai Debashis Sarker paul ross Department of Medical Oncology Guy's and St Thomas NHS Trust

Pancreatic ductal adenocarcinoma is an aggressive and devastating disease associated with poor survival outcomes. Even though signifcant advances have been made towards understanding the intricate pathology of this cancer, several important aspects remain unknown. Recently, key genetic mutations within the tumour have been identified, but the exact role they play in tumourigenesis has yet to be *** many years, the micro-tumour environment and stroma was thought to aid proliferation but there is now emerging research that suggests the contrary. Several novel targeted agents in pre-clinical and early clinical studies have been promising but it remains to be seen whether they will have a signifcant impact on patient outcomes. In this review we discuss the unique nature of pancreatic cancer biology, current treatment options and summarise the latest results from pre-clinical and clinical research. We also discuss the future strategies that are needed to improve outcomes for this disease.

关键词： Pancreatic cancer Adenocarcinoma Targeted therapy Genomics Stroma KRAS Chemotherapy

Limosilactobacillus mucosae FZJTZ26M3 prevents NAFLD in mice through modulation of lipid metabolism and gut microbiota dysbiosis

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Food Science and Human Wellness 2024年第3期13卷 1589-1601页

作者： Danting Dang Bowen Li Mengfan Ding Rpaul ross Catherine Stanton Jianxin Zhao Bo Yang Wei Chen State Key Laboratory of Food Science and Resources Jiangnan UniversityWuxi 214122China School of Food Science and Technology Jiangnan UniversityWuxi 214122China International Joint Research Center for Probiotics&Gut Health Jiangnan UniversityWuxi 214122China APC Microbiome Ireland University College CorkCork T12 YT20Ireland Teagasc Food Research Centre MooreparkFermoyCork T12 YT20Ireland National Engineering Research Center for Functional Food Jiangnan UniversityWuxi 214122China

Lactobacillus are considered promising therapeutic methods for nonalcoholic fatty liver disease(NAFLD).The effects of two strains of Ltmosilactobacillus mucosae on NAFLD were investigated in this ***-old male C57BL/6J mice were divided into 4 groups(n=8 per group,Control,Model,FZJTZ26M3,FGSYC17L3).*** FZJTZ26M3 reduced the mice 's body weight,liver weight,and adipose tissue weight after 12 weeks of *** to serum analysis,total cholesterol,triacylglycerol,and low-density lipoprotein cholesterol significantly decreased after *** FZJTZ26M3 *** pathology showed that *** FZJTZ26M3 was effective to ameliorate lipid deposition in NAFLD ***,the expression of the gene related to lipid metabolism in the liver and adipose tissue was analyzed,and the results indicated that *** FZJTZ26M3 could alleviate NAFLD by regulating lipid ***,the results of 16S rRNA gene sequencing revealed a drop in the relative abundance of Ruminococcaceae,which is linked to inflammation,but the relative abundance of a potential probiotic Akkermansia significantly increased after *** FZJTZ26M3 ***,*** FZJTZ26M3 could be a candidate to prevent NAFLD.

关键词： Limosilactobacillus mucosae Nonalcoholic fatty liver disease(NAFLD) Probiotic Lipid metabolism Gut microbiota

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Infant feces-derived Bifidobacterium breve CCFM1078 inhibits the occurrence of rheumatoid cachexia by IRS1/PI3K/Akt signaling pathway

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Food Science and Human Wellness 2024年

作者： Bowen Li Mengfan Ding Chen Chi Guoxun Shi Xiaoming Liu Jianxin Zhao paul ross Catherine Stanton Wei Chen Bo Yang State Key Laboratory of Food Science and Resources， Jiangnan University School of Food Science and Technology， Jiangnan University Department of Rheumatology， Jiangnan University Medical Center International Joint Research Center for Probiotics & Gut Health， Jiangnan University APC Microbiome Ireland， University College Cork Teagasc Food Research Centre National Engineering Research Center for Functional Food， Jiangnan University

This study aimed to investigate the effects of infant feces-derived Bifidobacterium breve CCFM1078 on rheumatoid cachexia （RC）. Twenty-four female Wistar rats were assigned to three groups: CON group （normal saline by gavage）， CIA group （collagen-induced arthritis， normal saline by gavage）， and CCFM1078 group (collagen-induced arthritis， 3×109CFU/rat/day B breve CCFM1078 gavage). The results demonstrated that B. breve CCFM1078 not only improved skeletal muscle function in CIA rats， but also modulated the gut microbiota， skeletal muscle metabolism and hormone levels， reduced inflammation in the knee joint and skeletal muscles， decreased activity of the NF-κB inflammatory signaling pathway， enhanced the IRS1/PI3K/Akt signaling pathway， promoted skeletal muscle differentiation， and maintained skeletal muscle fiber diameter， consequently slowing down the progression of RC. These findings suggested that B. breve CCFM1078 may have a beneficial role as part of a dietary intervention for RC， enhancing overall therapeutic effects.

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Bifidobacterium longum subsp. infantis CCFM1269 promotes intestinal barrier and release of IFN-β through TLR4-TRIF dependent way in growing mice

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Food Science and Human Wellness 2024年

作者： Mengfan Ding Bo Yang Bowen Li Haiqin Chen Renqiang Yu R.paul ross Catherine Stanton Shilong Jiang Jianxin Zhao Wei Chen State Key Laboratory of Food Science and Resources， Jiangnan University School of Food Science and Technology， Jiangnan University International Joint Research Center for Probiotics & Gut Health， Jiangnan University Department of Neonatology， Wuxi Maternity and Child Health Care Hospital， Affiliated Women's Hospital of Jiangnan University APC Microbiome Ireland， University College Cork Teagasc Food Research Centre Nutrition and Metabolism Research Division， Innovation Center， Heilongjiang Feihe Dairy Co.， Ltd. PKUHSC-China Feihe Joint Research Institute of Nutrition and Healthy Lifespan Development National Engineering Research Center for Functional Food， Jiangnan University

Bifidobacterium longum subsp. infantis is a commensal bacterium that predominates in the infant gut， playing a critical role in both preventing foreign infections and facilitating immune development. This study aimed to explore the effects of B. longum subsp. infantis supplementation on interferon-beta (IFN-β) secretion and intestinal barrier improvement in growing mice. Female and male mice were orally administered either saline or B. longum subsp. infantis CCFM1269 or I5TI (1 × 109CFU/mice per day， n = 8) from 1-week-age until 3-， 4-， and 5-week-age. RNA sequencing analysis revealed that CCFM1269 exhibited potential antiviral capacity through increasing 2’-5’ oligoadenylate synthetase (OAS). Additionally， CCFM1269 supplementation significantly increased colonic IFN-β levels which combined with OAS in 3-week-old female and male mice by activating the TLR4-TRIF-dependent signaling pathway. However， this effect was not observed in 4- and 5-week-old mice. Furthermore， both CCFM1269 were found to modulate the gut microbiota composition and enhance the intestinal barrier function in 3-， 4-， and 5-week-old mice. In summary， the results of this study suggested that B. longum subsp. infantis CCFM1269 promoting intestinal barrier and releasing IFN-β in growing mice was in a strain-specific and time-dependent manner.

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Bifidobacterium breve CCFM1078 regulates bone development in growing BALB/c mice via gut microbiota and metabolites to balance bone formation and resorption

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Food Science and Human Wellness 2024年

作者： Bowen Li Mengfan Ding Xiaoming Liu Haiqin Chen Jianxin Zhao R.paul ross Catherine Stanton Shilong Jiang Wei Chen Bo Yang State Key Laboratory of Food Science and Technology， Jiangnan University School of Food Science and Technology， Jiangnan University International Joint Research Center for Probiotics & Gut Health， Jiangnan University APC Microbiome Ireland， University College Cork Teagasc Food Research Centre Nutrition and Metabolism Research Division， Innovation Center， Heilongjiang Feihe Dairy Co.， Ltd. PKUHSC-China Feihe Joint Research Institute of Nutrition and Healthy Lifespan Development National Engineering Research Center for Functional Food， Jiangnan University

This study endeavors to investigate the effects of Bifidobacterium breve CCFM1078 on bone formation and resorption balance in growing BALB/c mice. Newborn BALB/c mice were assigned to the control group (administration saline) and the CCFM1078 group (administration B. breve CCFM1078， 3 × 109CFU/day) in 3-， 4-， and 5-week tests. All the groups have male and female distinctions. Our findings demonstrate that B. breve CCFM1078 exerts on the dynamic equilibrium between bone formation and resorption during the critical period of growth in mice by modulating the composition of gut microbiota and metabolites (hexadecanamide， linoleoyl ethanolamide， and palmitoyl ethanolamide)， the genes and proteins expression related to the GH/IGF-1 axis and Gs/PKA/CREB signaling pathways， as well as downstream osteogenic and osteoclastic differentiation factors. The effects of B. breve CCFM1078 were different with age and gender dependent. This finding suggests B. breve CCFM1078 may have potential applications in regulating bone metabolism in the growth period population.

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新月楼盘——离子艺术创造的标识和雕塑形成了新的发展形态

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广告大观(标识版) 2009年第1期 30-32页

作者： Greg Keshishian paul ross Tracy

德克萨斯州的奥斯汀市被称为全球现场音乐之都,但许多其他设施使它成为一个适合居住的地方。这座城市及其周边环境提供了一个美丽的地形,德州的中部和西部有许多山脉,河流和湖泊。但是,更重要的是职业发展机会,一个一流的大学和公共教... 详细信息

德克萨斯州的奥斯汀市被称为全球现场音乐之都,但许多其他设施使它成为一个适合居住的地方。这座城市及其周边环境提供了一个美丽的地形,德州的中部和西部有许多山脉,河流和湖泊。但是,更重要的是职业发展机会,一个一流的大学和公共教育系统,以及相对而言负担得起的住房提升了奥斯汀市在美国城市生活质量排名单上的位置。

关键词：雕塑德克萨斯州美术艺术楼盘离子奥斯汀

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航天飞机固体火箭发动机喷管的修复

固体火箭技术 1986年第2期 16-18页

作者： paul ross 李志明

为了保证航天飞机每次飞行的成本保持最低,设计时考虑了喷管的金属零件都要重复使用。因为这些零件都是由大型铝和钢锻件机加成的,成本都很高。如果能重复使用19次,喷管柔性接头重复使用9次,那么对于每次飞行来说,就能大幅度地降低成本... 详细信息

为了保证航天飞机每次飞行的成本保持最低,设计时考虑了喷管的金属零件都要重复使用。因为这些零件都是由大型铝和钢锻件机加成的,成本都很高。如果能重复使用19次,喷管柔性接头重复使用9次,那么对于每次飞行来说,就能大幅度地降低成本。航天飞机固体火箭发动机喷管是由作为支承件的大型铝和钢零件组成,这些零件内表面都粘结抗烧蚀绝热层.要重复使用的只是金属构件及柔性接头,因绝热层在工作期间要烧蚀、炭化,每次需重新更换。图1为喷管结构图,该喷管喉径136.86cm,全长424.7cm,出口直径369.9cm。这是当今固体发动机最大的喷管。喷管柔性接头的前法兰与后法兰及

关键词：柔性接头火箭发动机喷管航天飞机扩散段固定体

Novel,non-colonizing,single-strain live biotherapeutic product ADS024 protects against Clostridioides difficile infection challenge in vivo

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World Journal of Gastrointestinal Pathophysiology 2023年第4期14卷 71-85页

作者： Christopher K Murphy Michelle M O’Donnell James W Hegarty Sarah Schulz Colin Hill R paul ross Mary C Rea Ronald Farquhar Laurent Chesnel Research and Development Adiso Therapeutics Inc.ConcordMA 01742United States APC Microbiome Ireland University College CorkCork T12 K8AFIreland Teagasc Food Research Centre Moorepark FermoyCork P61 C996Ireland Executive Leadership Team Adiso Therapeutics Inc.ConcordMA 01742United States

BACKGROUND The Centers for Disease Control and Prevention estimate that Clostridioides difficile(***)causes half a million infections(CDI)annually and is a major cause of total infectious disease death in the United States,causing inflammation of the colon and potentially deadly *** recently reported the isolation of ADS024,a Bacillus velezensis(***)strain,which demonstrated direct in vitro bactericidal activity against ***,with minimal collateral impact on other members of the gut *** this study,we hypothesized that in vitro activities of ADS024 will translate in vivo to protect against CDI challenge in mouse *** To investigate the in vivo efficacy of *** ADS024 in protecting against CDI challenge in mouse *** To mimic disruption of the gut microbiota,the mice were exposed to vancomycin prior to dosing with *** the mouse single-dose study,the recovery of ADS024 was assessed via microbiological analysis of intestinal and fecal samples at 4 h,8 h,and 24 h after a single oral dose of 5×108 colony-forming units(CFU)/mouse of freshly grown *** single-dose study in miniature swine included groups that had been pre-dosed with vancomycin and that had been exposed to a dose range of ADS024,and a group that was not pre-dosed with vancomycin and received a single dose of *** ADS024 colonies[assessed by quantitative polymerase chain reaction(qPCR)using ADS024-specific primers]were counted on agar *** the 28-d miniature swine study,qPCR was used to measure ADS024 levels from fecal samples after oral administration of ADS024 capsules containing 5×109 CFU for 28 consecutive days,followed by MiSeq compositional sequencing and bioinformatic analyses to measure the impact of ADS024 on *** studies were performed to determine the efficacy of ADS024 in a mouse model of CDI:Study 1 to determine the effects of fresh ADS024 culture and ADS024 spore preparations on the clinical mani

关键词： Gut Single-strain live biotherapeutic product ADS024 Clostridioides difficile Clostridioides difficile challenge model Microbiota