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clostridium butyricum alleviates intestinal low-grade inflammation in TNBS-induced irritable bowel syndrome in mice by regulating functional status of lamina propria dendritic cells

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World Journal of Gastroenterology 2019年第36期25卷 5469-5482页

作者： Qin Zhao Wen-Rong Yang Xiao-Hong Wang Gai-Qin Li Lei-Qi Xu Xiao Cui Yang Liu Xiu-Li Zuo Department of Gastroenterology Qilu Hospital Shandong University Jinan 250012 Shandong Province China Department of Gastroenterology Taian City Central Hospital Taian 271000 Shandong Province China Department of Clinical Nutrition Taian City Central Hospital Taian 271000 Shandong Province China Department of Medicine Beijing 316 Hospital Beijing 100093 China

BACKGROUND Irritable bowel syndrome (IBS) is one of the most common functional gastroenterological diseases characterized by abnormal visceral sensitivity and lowgrade inflammation. The role of clostridium butyricum (C. butyricum) in reducing intestinal low-grade inflammation via immune pathways has been well defined. However, the detailed mechanisms of the effects of C. butyricum on intestinal mucosal immunity, especially on immune cells of the lamina propria, remain unclear. Dendritic cells (DCs), which are important immune cells, secrete proinflammatory cytokines (IL-1β, IL-6, and others) and express T cell immunoglobulin and mucin domain-3 (TIM3), promoting proliferation and activation of DCs, and mediating Th1 and Th17 inflammatory responses. AIM To investigate the role of DCs in the development of IBS in a rat model and to understand the regulation of DCs after C. butyricum intervention. METHODS An IBS animal model was established using C57BL/6 mice, and C. butyricum was continuously administered via the intragastric route to simulate different intestinal immune states. Intestinal visceral hypersensitivity and histopathology were assessed using the abdominal withdrawal reflex (AWR) test and hematoxylin & eosin (H&E) staining, respectively. The expression of proinflammatory cytokines (IL-1β and IL-6) and TIM3 was analyzed by Western blot analysis and real-time PCR. Flow cytometry was applied to analyze the quantity, function, and membrane molecule TIM3 of the lamina propria dendritic cells (LPDCs). The regulatory effect of C. butyricum was verified in bone marrowderived dendritic cells by in vitro experiments. RESULTS The secretion of proinflammatory cytokines (IL-1β and IL-6) in mice with IBS was significantly increased compared with that of the control group, which suggested that the intestinal mucosa in mice with IBS was in a low-grade inflammatory state. The expression of CD11C+CD80+ and CD11c+TIM3+ in intestinal LPDCs in mice with IBS increased significant

关键词： clostridium butyricum Irritable bowel syndrome Lamina propria dendritic cells T cell immunoglobulin and mucin domain-3 Proinflammatory cytokines

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clostridium difficile and inflammatory bowel disease: Role in pathogenesis and implications in treatment

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World Journal of Gastroenterology 2013年第43期19卷 7577-7585页

作者： Orna Nitzan Mazen Elias Bibiana Chazan Raul Raz Walid Saliba Infectious Disease Unit Ha’emek Medical CenterAfula 18101Israel Bruce Rappaport Faculty of Medicine Technion-Israel Institute of TechnologyHaifa 31096Israel Department of Internal Medicine C Ha’emek Medical CenterAfula 18101Israel

clostridium difficile(***)is the leading cause of antibiotic associated colitis and nosocomial *** with inflammatory bowel disease(IBD)are at increased risk of developing *** infection(CDI),have worse outcomes of CDI-including higher rates of colectomy and death,and experience higher rates of ***,it is still not clear whether *** is a cause of IBD or a consequence of the inflammatory state in the intestinal *** burden of CDI has increased dramatically over the past decade,with severe outbreaks described in many countries,which have been attributed to a new and more virulent strain.A parallel rise in the incidence of CDI has been noted in patients with *** patients with CDI tend be younger,have less prior antibiotic exposure,and most cases of CDI in these patients represent outpatient acquired *** clinical presentation of CDI in these patients can be unique-including diversion colitis,enteritis and pouchitis,and typical findings on colonoscopy are often *** to the high prevalence of CDI in patients hospitalized with an IBD exacerbation,and the prognostic implications of CDI in these patients,it is recommended to test all IBD patients hospitalized with a disease flare for *** includes general measures such as supportive care and infection control *** therapy with either oral metronidazole,vancomycin,or the novel antibiotic-fidaxomicin,should be initiated as soon as *** macrobiota transplantation constitutes another optional treatment for severe/recurrent *** aim of this paper is to review recent data on CDI in IBD:role in pathogenesis,diagnostic methods,optional treatments,and outcomes of these patients.

关键词： clostridium difficile Diarrhea Inflammatory bowel disease Pathogenesis Treatment

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clostridium difficile infection and inflammatory bowel disease:Understanding the evolving relationship

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World Journal of Gastroenterology 2010年第39期16卷 4892-4904页

作者： Udayakumar Navaneethan Preethi GK Venkatesh Bo Shen Victor W.Fazio Center for Inflammatory Bowel Disease Department of GastroenterologyDigestive Disease Institutethe Cleveland Clinic Foundation

clostridium difficile(***)infection(CDI)is the leading identifiable cause of antibiotic-associated *** there is an alarming trend of increasing incidence and severity of CDI in the United States and Europe,superimposed CDI in patients with inflammatory bowel disease(IBD)has drawn considerable attention in the gastrointestinal *** majority of IBD patients appear to contract CDI as *** affects disease course of IBD in several ways,including triggering disease flares,sustaining activity,and in some cases,acting as an"innocent"*** its wide spectrum of presentations,CDI has been reported to be associated with a longer duration of hospitalization and a higher mortality in IBD *** patients with restorative proctocolectomy or with diverting ileostomy are not immune to CDI of the small bowel or ileal *** immunomodulator or corticosteroid therapy for IBD should be continued in patients with superimposed CDI is *** appears that more adverse outcomes was observed among patients treated by a combination of immunomodulators and antibiotics than those treated by antibiotics *** use of biologic agents does not appear to increase the risk of acquisition of *** CDI in the setting of underlying IBD,vancomycin appears to be more efficacious than *** controlled trials are required to clearly define the appropriate management for CDI in patients with IBD.

关键词： clostridium difficile Inflammatory bowel disease Antibiotics Colectomy

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clostridium difficile infection in the community:Are proton pump inhibitors to blame?

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World Journal of Gastroenterology 2013年第40期19卷 6710-6713页

作者： Daniel E Freedberg Julian A Abrams Division of Digestive and Liver Diseases Columbia University Medical CenterNew YorkNY 10032United States

Once a nosocomial disease,clostridium difficile infection(CDI)now appears frequently in the community in the absence of exposure to *** studies have shown that patients with community-acquired CDI are younger,more likely to be female,and have fewer comorbidities compared to patients with hospital-associated *** most studies of CDI are hospitalbased,comparatively little is known about communityacquired *** recent study by Chitnis has received widespread attention because it used active surveillance to capture all cases of community-acquired CDI within a large population and assessed key risk *** authors found that low-level healthcare exposure and proton pump inhibitor use were common among those with non-antibiotics associated,community-acquired *** this commentary,we discuss the changing epidemiology of community-acquired CDI and the evidence basis for the controversial association between proton pump inhibitors and community-acquired CDI.

关键词： clostridium difficile Pseudomembranous enterocolitis Proton pump inhibitors Anti-bacterial agents Pharmacoepidemiology Public health Disease outbreaks Epidemics

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clostridium difficile-associated disease:Adherence with current guidelines at a tertiary medical center

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World Journal of Gastroenterology 2013年第46期19卷 8647-8651页

作者： Bryan F Curtin Yousef Zarbalian Mark H Flasar Erik von Rosenvinge Resident in Internal Medicine Department of Medicine University of Maryland School of Medicine Baltimore Division of Gastroenterology and Hepatology Department of Medicine University of Maryland School of Medicine and VA Maryland Health Care System Baltimore

AIM:To assess adherence with the the Society for Healthcare Epidemiology of America(SHEA)/the Infectious Diseases Society of America(IDSA)guidelines for management of clostridium difficile(***)-associated disease(CDAD)at a tertiary medical ***:All positive *** stool toxin assays in adults between May 2010 and May 2011 at the University of Maryland Medical Center were *** episodes were classified as guideline adherent or nonadherent and these two groups were compared to determine demographic and clinical factors predictive of *** regression analysis was performed to assess the effect of multiple predictors on guideline ***:320 positive *** stool tests were identified in 290 *** by disease severity criteria set forth by the SHEA/IDSA guidelines,42.2%of cases were mild-moderate,48.1%severe,and 9.7%*** adherence with the guidelines was observed in only 43.4%of *** was65.9%for mild-moderate CDAD,which was significantly better than in severe cases(25.3%)or severe-complicated cases(35.5%)(P<0.001).There was no difference in demographics,hospitalization,ICU exposure,recurrence or 30-d mortality between adherent and non-adherent groups.A multivariate model revealed significantly decreased adherence for severe or severecomplicated episodes(OR=0.18,95%CI:0.11-0.30)and recurrent episodes(OR=0.46,95%CI:0.23-0.95).CONCLUSION:Overall adherence with the SHEA/IDSA guidelines for management of CDAD at a tertiary medical center was poor;this was most pronounced in severe,severe-complicated and recurrent *** interventions aimed at improving guideline adherence are warranted.

关键词： clostridium difficile Metronidazole Vanco-mycin Adherence to the Infectious Diseases Society of America Guidelines Hospital Acquired Infections

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Extraction of electrons by magnetite and ferrihydrite from hydrogen-producing clostridium bifermentans by strengthening the acetate production pathway

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Science China(Technological Sciences) 2019年第10期62卷 1719-1725页

作者： ZHANG YueChao LIU FangHua XU HengDuo XIAO LeiLei Key Laboratory of Coastal Biology and Biological Resources Utilization Yantai Institute of Coastal Zone ResearchChinese Academy ofSciencesYantai264003China Laboratory for Marine Biology and Biotechnology Qingdao National Laboratory for Marine Science and TechnologyQingdao266237China University of Chinese Academy of Sciences Beijing100049China

Conductive mineral nanoparticles, such as magnetite, can promote interspecies electron transfer between syntrophic ***, the effect of magnetite has only been inferred in intraspecific electron output. Herein, a hydrogen-producing strain,namely, clostridium bifermentans, which holds several electron output pathways, was used to study the effect of magnetite on the intraspecific electron output manner. Additionally, insulated amorphous ferrihydrite, which was used as an extracellular electron acceptor, was selected to compare with magnetite. Electrons, which were originally used to generate hydrogen, were shunted with the addition of magnetite and ferrihydrite, which resulted in the reduction of hydrogen production and accumulation of Fe(II). Interestingly, more electrons(39.7% and 53.5%) were extracted by magnetite and ferrihydrite, respectively, which led to less production of butyrate and more acetate. More importantly, the increased electron extraction efficiency suggested that electroactive microorganisms can switch metabolic pathways to adapt to electron budget pressure in intraspecific systems. This work broadens the understanding of the interaction between iron oxides and fermentative hydrogen-producing microbes that hold the capacity of Fe(III) reduction.

关键词： magnetite ferrihydrite Fe(III) reduction electron extraction increased acetate production clostridium bifermentans

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Effects of Bacillus coagulans supplementation on the growth performance and gut health of broiler chickens with clostridium perfringens-induced necrotic enteritis

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Journal of Animal Science and Biotechnology 2018年第2期9卷 407-420页

作者： Yuanyuan Wu Yujing Shao Bochen Song Wenrui Zhen Zhong Wang Yuming Guo Muhammad Suhaib Shahid Wei Nie State Key Laboratory of Animal Nutrition College of Animal Science and Technology China Agricultural University College of Biology China Agricultural University

Background: The poultry industry is in need of effective antibiotic alternatives to control outbreaks of necrotic enteritis(NE) due to clostridium ***: This study was conducted to investigate the effects of feeding Bacil us coagulans on the growth performance and gut health of broiler chickens with C. perfringens-induced NE. Two hundred and forty 1-day-old broiler chicks were randomly assigned to a 2 × 2 factorial arrangement with two dietary B. coagulans levels(0 or 4 × 109 CFU/kg of diet) and two disease chal enge statuses(control or NE chal enged).Results: NE-induced reduction in body weight gain was relieved by the addition of B. coagulans into broiler diets compared with the NE-infected birds. NE infection damaged intestinal morphological structure, promoted intestinal *** growth and liver invasion, and enhanced anti-C. perfringens specific sI gA concentrations in the gut and specific IgG levels in serum compared with the uninfected birds. NE infection significantly(P < 0.05) decreased mucin-2(at 14 d post-infection(DPI), tol-like receptor 2(TLR2, at 7 and 14 DPI), TLR4(at 7 and 14 DPI), tumor necrosis factor super family15(TNFSF15, at 7 and 14 DPI), lysozyme(LYZ, at 14 DPI) and fowlicidin-2(at 7 and 14 DPI) mR NA levels, whereas it dramatical y(P = 0.001) increased IFN-γ mR NA levels at 7 DPI. However, chal enged birds fed diets supplemented with *** showed a significant(P < 0.01) decrease in gut lesion scores, decreased C. perfringens numbers in the cecum and liver, and an increase in fowlicidin-2 mR NA levels in compared with the uninfected birds. In addition, compared with the non-supplemented group, dietary inclusion of B. coagulans improved intestinal barrier structure, further increased specific sI gA levels and alkaline phosphatase(IAP) activity in the jejunum, enhanced the expression of jejunum lysozyme mR NA, and inhibited the growth, colonization, and invasion of C. perfringens; in contrast, it reduced serum-specific

关键词： Bacillus coagulans Broiler chickens clostridium perfringens Gut health

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In vivo and in vitro protective effect of arginine against intestinal inflammatory response induced by clostridium perfringens in broiler chickens

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Journal of Animal Science and Biotechnology 2020年第1期11卷 81-94页

作者： Beibei Zhang Liping Gan Muhammad Suhaib Shahid Zengpeng Lv Hao Fan Dan Liu Yuming Guo State Key Laboratory of Animal Nutrition College of Animal Science and TechnologyChina Agricultural UniversityBeijing 100193People’s Republic of China

Background:Necrotic enteritis is a widespread disease in poultry caused by clostridium *** previously reported that dietary arginine supplementation protected the intestinal mucosa of broiler chickens with necrotic enteritis,but the related protective mechanisms remain *** in vivo trial was designed as a 2×2 factorial arrangement to evaluated the effects of arginine supplementation on inflammatory responses,arginine transporters,arginine catabolism and JAK-STAT signalling pathway in broiler chickens challenged with *** or without ***,we validated the in vivo results using intestinal epithelial cells of chicken ***:*** infection markedly increased gut gross pathological and histopathological lesion scores,promoted liver *** invasion,reduced serum arginine levels,and elevated jejunal mucosal lysozyme activities(P<0.05),but these effects were significantly reversed by arginine supplementation in vivo(P<0.05).The challenge significantly increased serum procalcitonin levels,jejunal mucosal iNOS activities and jejunal IL-6,TGF-β3,cationic amino acid transporter(CAT)-1,and CAT-3 mRNA expression(P<0.05),whereas arginine supplementation significantly reduced jejunal IFN-γ,IL-1β,IL-6,IL-10,TGF-β3,and CAT-3 mRNA expression(P<0.05).Arginine supplementation significantly attenuated the *** challenge-induced increases in jejunal i NOS,arginase 2,arginine decarboxylase,arginine:glycine amidinotransferase,JAK1,JAK3,STAT1,and STAT6 mRNA expression(P<0.05).The in vitro experiment showed that *** challenge markedly increased cellular cytotoxicity and the mRNA expression of IL-1β,IL-8,IL-10,CAT-1 and CAT-3(P<0.05),which were significantly reversed by 50μmol/L and/or400μmol/L arginine pre-treatment(P<0.05).Conclusions:Arginine prevented *** challenge-induced circulated arginine deficiency,normalized intestinal arginine transport and catabolism,down-regulated JAK-STAT signalli

关键词： Arginine Broiler chickens clostridium perfringens Intestine inflammatory response Metabolism

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Single and multiplexed gene repression in solventogenic clostridium via Cas12a-based CRISPR interference

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Synthetic and Systems Biotechnology 2023年第1期8卷 148-156页

作者： Rochelle Carla Joseph Nicholas R.Sandoval Department of Chemical and Biomolecular Engineering Tulane UniversityNew OrleansLA70118United States

The Gram-positive,spore-forming,obligate anaerobic firmicute species that make up the clostridium genus have broad feedstock consumption capabilities and produce value-added metabolic products,but genetic manipulation is difficult,limiting their broad ***-Cas systems have recently been applied to clostridium species,primarily using Cas9 as a counterselection marker in conjunction with plasmid-based homologous *** interference is a method that reduces gene expression of specific genes via precision targeting of a nuclease deficient Cas effector ***,we develop a dCas12a-based CRISPR interference system for transcriptional gene repression in multiple mesophilic clostridium *** show the Francisella novicida Cas12a-based system has a broader applicability due to the low GC content in clostridium species compared to CRISPR Cas systems derived from other *** demonstrate>99%reduction in transcript levels of targeted genes in clostridium acetobutylicum and>75%reduction in clostridium *** also demonstrate multiplexed repression via use of a single synthetic CRISPR array,achieving 99%reduction in targeted gene expression and elucidating a unique metabolic profile for their reduced ***,this work builds a foundation for high throughput genetic screens without genetic editing,a key limitation in current screening methods used in the clostridium community.

关键词： CRISPR Cas12a clostridium CRISPRi

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Co-morbidity,not age predicts adverse outcome in clostridium difficile colitis

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World Journal of Gastroenterology 2000年第2期6卷 198-201页

作者： TS Dharmarajan M Sipalay R Shyamsundar EP Norkus CS Pitchumoni Divisions of Geriatrics Our Lady of Mercy Medical Center BronxNew YorkUSA Department of Biomedical Research Our Lady of Mercy Medical CenterBronxNew YorkUSA Divisions of Gastroenterology Our Lady of Mercy Medical Center BronxNew YorkUSA

AIM To examine whether age alone or co-morbidity is a risk factor for death in olderadults who developed clostridium difficile(Cd)colitis during *** A retrospective,observationalstudy design was performed in our Lady ofMercy Medical Center,a 650-bed,urban,community-based,university-affiliated teachinghospital.121 patients with a positive diagnosisof Cd colitis Caged 23-97 years)were studied,and data pertinent to demographic variables,medical history,co-morbidity,physicalexamination,and laboratory results *** was examined as a continuousvariable and stratified into Age1(80 years).However,age,per se,had no effect onmortality.A history of cardiac disease(P=0.036),recurrent or refractory infection>4weeks(P=0.007),low serum total protein(P=0.034),low serum albumin(P=0.001),antibiotic use >4 weeks(P<0.010),use of over 4 antibiotics(P=0.026),and use of certainclasses of antibiotics(P=0.035-0.004)werepredictive of *** was stronglypredicted by the use of penicillin-like antibioticsplus clindamycin,in the presence ofhypoalbuminemia,refractory sepsis,andcardiac disease(P=0.00005).CONCLUSION Cd colitis is common in the ***,unlike co-morbidity,age alonedoes not affect the clinical outcome(survival vsdeath).

关键词： clostridium difficile colitis/old age comorbidity/old age diarrhea colitis/therapy physical examination

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