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Food Science and Human Wellness 2024年

作者： Chi Chen Bowen Li Mengfan Ding Huizhen Li Jianxin Zhao r.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 International Joint research Center for Probiotics & Gut Health Jiangnan University APC Microbiome Ireland University College Cork Teagasc Food research Centre Moorepark National Engineering research Center for Functional Food Jiangnan University

Irritable bowel syndrome-diarrhea （IBS-D） is a prevalent functional bowel disease severely impairs the quality of life of patients. Visceral hypersensitivity （VH） is the main symptom of IBS-D. Probiotics have been found to effectively alleviate VH. In this study， neonatal maternal separation （NMS） was used to induce VH in 72 rats and investigated the effects of daily gavage of 3*109CFU of Lactobacillus and Bifidobacterium on alleviating the symptoms of IBS-D and behavioral interventions， as well as exploring potential mechanisms. The results demonstrated that Lactobacillus acidophilus and Bifidobacterium breve could alleviate the symptoms of IBS-D such as VH and increased frequency of bowel movements， as well as improving non-spatial memory in NMS rats. These effects were achieved by modulating the composition of gut microbiota and metabolites （including short-chain fatty acids， deoxycholic acid and adenosine）， and by regulating the expression of genes and proteins associated with the NGF/TrkA signaling pathway， tryptophan metabolism， and inflammatory factors in the hippocampus. This finding suggests that Lactobacillus acidophilus and Bifidobacterium breve have promising potential for the alleviation of IBS.

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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 Nutrition and Metabolism research Division Innovation Center Heilongjiang Feihe Dairy Co. Ltd. National Engineering research Center for Functional Food Jiangnan University State Key Laboratory of Food Science and Technology Jiangnan University PKUHSC-China Feihe Joint research Institute of Nutrition and Healthy Lifespan Development APC Microbiome Ireland University College Cork School of Food Science and Technology Jiangnan University International Joint research Center for Probiotics & Gut Health Jiangnan University Teagasc Food research Centre

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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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 Teagasc Food research Centre Nutrition and Metabolism research Division Innovation Center Heilongjiang Feihe Dairy Co. Ltd. Department of Neonatology Wuxi Maternity and Child Health Care Hospital Affiliated Women's Hospital of Jiangnan University National Engineering research Center for Functional Food Jiangnan University School of Food Science and Technology Jiangnan University PKUHSC-China Feihe Joint research Institute of Nutrition and Healthy Lifespan Development International Joint research Center for Probiotics & Gut Health Jiangnan University APC Microbiome Ireland University College Cork

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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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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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

Protective Effects of Bifidobacterium breve on IMQ-Induced Psoriasis in Mice through Secondary Bile Acid Production and FXr-TLr4/NF-κB Pathway

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Food Science and Human Wellness 2023年

作者： Xinqi Chen Yang Chen Catherine Stanton r.paul ross Jianxin Zhao Bo Yang Wei Chen National Engineering research Center for Functional Food Jiangnan University School of Food Science and Technology Jiangnan University State Key Laboratory of Food Science and Technology Jiangnan University APC Microbiome Ireland University College Cork Teagasc Food research Centre International Joint research Center for Probiotics & Gut Health Jiangnan University

This study aimed to evaluate the effects of Bifidobacterium breve CCFM683 on psoriasis and to investigate the underlying mechanisms. Bifidobacterium breve CCFM683 significantly ameliorated psoriasis in mice as well as elevated the deoxycholic acid (DCA) and lithocholic acid (LCA) in the colon compared with those of the imiquimod-treated mice. Meanwhile， B. breve CCFM683 increased the relative abundance of DCA-producing Lachnoclostridium and diminished the harmful Desulfovibrio and Prevotellaceae UCG001. Additionally， the farnesoid X receptor (FXr) in the skin was activated and the expression of the TLr4/NF-κB pathway was inhibited， and the downstream IL-17 and TNF-α were downregulated whereas IL-10 was up-regulated . Moreover， the subsequent hyperproliferation of keratinocytes and the dysfunction of the epidermal barrier were improved. In conclusion， CCFM683 administration ameliorated IMQ-induced psoriasis via modulating gut microbiota， promoting the DCA production， regulating the FXr-TLr4/NF-κB pathway， diminishing proinflammatory cytokines， and regulating keratinocytes and epidermal barrier. These findings may be conducive to elucidating the mechanism for probiotics to ameliorate psoriasis and to promote its clinical trials in skin disease.

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Testosterone therapy reduces hepatic steatosis in men with type 2 diabetes and low serum testosterone concentrations

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World Journal of Hepatology 2022年第4期14卷 754-765页

作者： ross Apostolov Emily Gianatti Darren Wong Numan Kutaiba paul Gow Mathis Grossmann Marie Sinclair Department of Gastroenterology and Liver Transplant Unit Austin HealthHeidelberg 3084VICAustralia Department of Medicine University of MelbourneParkville 3010VICAustralia Department of Endocrinology Fiona Stanley HospitalMurdoch 6150WAAustralia Department of radiology Austin HealthHeidelberg 3084VICAustralia Department of Endocrinology Austin HealthHeidelberg 3084VICAustralia

BACKGrOUND Non-alcoholic fatty liver disease(NAFLD)is highly prevalent in people with diabetes with no available *** To explore the effect of testosterone treatment on *** therapy improves insulin resistance and reduces total body fat,but its impact on the liver remains poorly *** This secondary analysis of a 40 wk,randomised,double-blinded,placebocontrolled trial of intramuscular testosterone undecanoate in men with type 2 diabetes and lowered serum testosterone concentrations evaluated the change in hepatic steatosis as measured by liver fat fraction on magnetic resonance imaging(MrI).rESULTS Of 88 patients enrolled in the index study,39 had liver MrIs of whom 20 received testosterone therapy and 19 received *** patients had>5%hepatic steatosis at baseline and 38 of 39 patients met diagnostic criteria for *** liver fat at baseline was 15.0%(IQr 11.5%-21.1%)in the testosterone and 18.4%(15.0%-28.9%)in the placebo *** ALT was 34units/L(26-38)in the testosterone and 32units/L(25-52)in the placebo *** week 40,patients receiving testosterone had a median reduction in absolute liver fat of 3.5%(IQr 2.9%-6.4%)compared with an increase of 1.2%in the placebo arm(between-group difference 4.7%Pr controlling for baseline liver fat,testosterone therapy was associated with a relative reduction in liver fat of 38.3%(95%confidence interval 25.4%-49.0%,Prone therapy was associated with a reduction in hepatic steatosis in men with diabetes and low serum *** randomised studies of testosterone therapy in men with NAFLD focusing on liver-related endpoints are therefore justified.

关键词： Hepatic steatosis Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Testosterone therapy Testosterone undecanoate Type 2 diabetes

reduced upper limb lean mass on dual energy X-ray absorptiometry predicts adverse outcomes in male liver transplant recipients

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World Journal of Transplantation 2022年第6期12卷 120-130页

作者： Penelope Hey rudolf Hoermann paul Gow Timothy P Hanrahan Adam G Testro ross Apostolov Marie Sinclair Liver Transplant Unit Austin HealthHeidelberg 3084Australia Department of Medicine University of MelbourneMelbourne 3052Australia

BACKGrOUND Pre-transplant muscle wasting measured by computed tomography has been associated with adverse clinical outcomes after liver transplantation including increased rates of sepsis and hospitalisation *** limb lean mass(LM)measured by dual-energy X-ray absorptiometry(DEXA)was recently identified as a novel predictor of sarcopenia-associated mortality in men waitlisted for *** To investigate the use of DEXA LM in predicting gender-stratified early posttransplant *** Liver transplant recipients who underwent pre-transplant DEXA body composition imaging between 2002 and 2017 were *** included posttransplant mortality and graft failure,bacterial infections,acute cellular rejection(ACr)and intensive care and total hospital length of *** Four hundred and sixty-nine patients met inclusion criteria of which 338 were male(72%).Median age was 55.0 years(interquartile range 47.4,59.7)and model for end-stage liver disease(MELD)score *** time from assessment to transplantation was 7 mo(3.5,12).Upper limb LM was inversely associated with bacterial infections at 180 d post-transplant(hazard ratio=0.42;95%confidence interval:0.20-0.89;P=0.024)in males *** was a negative correlation between upper limb LM and intensive care(τb=-0.090,P=0.015)and total hospital length of stay(τb=-0.10,P=0.0078)in *** women,neither MELD nor body composition parameters were associated with post-transplant adverse outcomes or increased length of *** composition parameters,MELD and age were not associated with 90-d mortality or graft failure in either *** were no significant predictors of early *** Sarcopenia is an independent and potentially modifiable predictor of increased post-transplant bacterial infections and hospital length of stay in men with *** upper limb LM provides a novel measure of muscle wasting that has prognostic value in this *** lack of association in women req

关键词： Dual-energy X-ray absorptiometry Sarcopenia Body composition Liver transplantation Survival

Transcriptome Analysis of Arabidopsis Wild-Type and gl3-sst sim Trichomes Identifies Four Additional Genes required for Trichome Development

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Molecular Plant 2009年第4期2卷 803-822页

作者： M. David Marks Jonathan r Wenger Edward Gilding ross Jilk richard A. Dixon Department of Plant Biology University of Minnesota St Paul MN 551108 USA Department of Chemistry University of Wisconsin-River Falls River Falls Wl 54022 USA Plant Biology Division Samuel Roberts Noble Foundation Ardmore OK 73401 USA

Transcriptome analyses have been performed on mature trichomes isolated from wild-type Arabidopsis leaves and on leaf trichomes isolated from the g13-sst sim double mutant, which exhibit many attributes of immature trichomes. The mature trichome profile contained many highly expressed genes involved in cell wall synthesis, protein turnover, and abiotic stress response. The most highly expressed genes in the g13-sst sim profile encoded ribosomal proteins and other proteins involved in translation. Comparative analyses showed that all but one of the genes encoding transcription factors previously found to be important for trichome formation, and many other trichome-important genes, were preferentially expressed in gl3-sst sim trichomes. The analysis of genes preferentially expressed in gl3-sst sim led to the identification of four additional genes required for normal trichome development. One of these was the HDG2 gene, which is a member of the HD-ZIP IV transcription factor gene family. Mutations in this gene did not alter trichome expansion, but did alter mature trichome cell walls. Mutations in BIT resulted in a loss of trichome branch formation. The relationship between bit and the phenotypically identical mutant, sti, was explored. Mutations in PEL3, which was previously shown to be required for development of the leaf cuticle, resulted in the occasional tangling of expanding trichomes. Mutations in another gene encoding a protein with an unknown function altered trichome branch formation.

关键词： Cell wall cell differentiation homeodomain wax trichome

Molecularly targeted therapy for advanced hepatocellular carcinoma-a drug development crisis?

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World Journal of Gastrointestinal Oncology 2016年第2期8卷 173-185页

作者： Kiruthikah Thillai paul ross Debashis Sarker department of medical oncology guy’s and st thomas nhs trustLondon SE1 9RTUnited Kingdom division of cancer studies king’s college londonguy’s hospitalLondon SE1 9RTUnited Kingdom institute of liver studies king’s college hospital nhs trustLondon SE5 9RSUnited Kingdom

Hepatocellular carcinoma is the fastest growing cause of cancer related death globally. Sorafenib,a multitargeted kinase inhibitor,is the only drug proven to improve outcomes in patients with advanced disease offering modest survival benefit. Although comprehensive genomic mapping has improved understanding of the genetic aberrations in hepatocellular cancer(HCC),this knowledge has not yet impacted clinical care. The last few years have seen the failure of several first and second line phase Ⅲ clinical trials of novel molecularly targeted therapies,warranting a change in the way new therapies are investigated in HCC. Potential reasons for these failures include clinical and molecular heterogeneity,trial design and a lack of biomarkers. This review discusses the current crisis in HCC drug development and how we should learn from recent trial failures to develop a more effective personalised treatment paradigm for patients with HCC.

关键词： Hepatocellular carcinoma Molecular targets Genomics Sorafenib Tyrosine kinase inhibitors