Pub Date : 2026-01-22DOI: 10.1016/j.anaerobe.2026.103023
Xiaoxia Zhang, Min Quan, Zhiyong Zong, Xiaohui Wang
UDCA exhibits limited direct bacteriostatic activity against Clostridioides difficile with a high MIC90 of >128 μg/mL against 121 clinical strains. However, compared with vancomycin, UDCA significantly impedes biofilm formation and bacterial adherence at subinhibitory concentrations, which may be the therapeutic advantages of UDCA and support this old drug to be further developed for CDI prevention.
{"title":"Ursodeoxycholic acid inhibits biofilm formation and bacterial adhesion of Clostridioides difficile.","authors":"Xiaoxia Zhang, Min Quan, Zhiyong Zong, Xiaohui Wang","doi":"10.1016/j.anaerobe.2026.103023","DOIUrl":"https://doi.org/10.1016/j.anaerobe.2026.103023","url":null,"abstract":"<p><p>UDCA exhibits limited direct bacteriostatic activity against Clostridioides difficile with a high MIC<sub>90</sub> of >128 μg/mL against 121 clinical strains. However, compared with vancomycin, UDCA significantly impedes biofilm formation and bacterial adherence at subinhibitory concentrations, which may be the therapeutic advantages of UDCA and support this old drug to be further developed for CDI prevention.</p>","PeriodicalId":8050,"journal":{"name":"Anaerobe","volume":" ","pages":"103023"},"PeriodicalIF":2.6,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Expression of concern: “Pyrosequencing study of fecal microflora of autistic and control children”","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":8050,"journal":{"name":"Anaerobe","volume":"97 ","pages":"Article 103033"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147396002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-09-12DOI: 10.1016/j.anaerobe.2025.102996
Camila Fonseca Rizek , Marina Farrel Côrtes , Bianca Helena Ventura Fernandes , Silvia Figueiredo Costa , Evelyne Santana Girão , Roberta Cristina Martins , Sânia Alves dos Santos , Bruno de Melo Tavares , Luciani Silveira de Carvalho , Cecilia Leite Costa , Daniely Viana Costa , Geovania Maciel , Gerly Anne de Castro Brito , Lauro Vieira Perdigão Neto
Objectives
Clostridioides difficile is a major cause of nosocomial diarrhea, and its virulence is typically attributed to the production of toxins. However, other genomic factors may contribute to its pathogenicity. To study the in vivo aspects of C. difficile infection, various animal models have been employed. Zebrafish (Danio rerio) offers several advantages over mammalian models, but there are still few studies using it to evaluate C. difficile infection. Here, we aimed to explore in vivo virulence differences among clinical strains by employing the zebrafish embryo model using eight sequenced C. difficile isolates with distinct genomic profiles.
Methods
Embryos were microinjected with bacterial suspensions, and mortality and cardiac edema were monitored over 96 h. Survival and cardiotoxicity were assessed and correlated with whole-genome data and clinical outcomes.
Results
Two strains exhibited distinct pathogenic effects: HC48 (ST42) caused significantly increased mortality (p < 0.0001), and HC132 (ST669) induced cardiotoxicity in 20 % of embryos. Surprisingly, the hypervirulent control strain NAP1/027 did not produce enhanced virulence in this model.
Conclusion
While zebrafish embryos showed promise for distinguishing strain-specific virulence, limitations such as colonization capacity and host–microbe interactions suggest that further research is needed to validate this model for C. difficile virulence testing.
{"title":"Zebrafish as an in vivo model to study the pathogenicity of Clostridioides difficile clinical strains","authors":"Camila Fonseca Rizek , Marina Farrel Côrtes , Bianca Helena Ventura Fernandes , Silvia Figueiredo Costa , Evelyne Santana Girão , Roberta Cristina Martins , Sânia Alves dos Santos , Bruno de Melo Tavares , Luciani Silveira de Carvalho , Cecilia Leite Costa , Daniely Viana Costa , Geovania Maciel , Gerly Anne de Castro Brito , Lauro Vieira Perdigão Neto","doi":"10.1016/j.anaerobe.2025.102996","DOIUrl":"10.1016/j.anaerobe.2025.102996","url":null,"abstract":"<div><h3>Objectives</h3><div><em>Clostridioides difficile</em> is a major cause of nosocomial diarrhea, and its virulence is typically attributed to the production of toxins. However, other genomic factors may contribute to its pathogenicity. To study the <em>in vivo</em> aspects of <em>C. difficile</em> infection, various animal models have been employed. Zebrafish (<em>Danio rerio</em>) offers several advantages over mammalian models, but there are still few studies using it to evaluate <em>C. difficile</em> infection. Here, we aimed to explore <em>in vivo</em> virulence differences among clinical strains by employing the zebrafish embryo model using eight sequenced <em>C. difficile</em> isolates with distinct genomic profiles.</div></div><div><h3>Methods</h3><div>Embryos were microinjected with bacterial suspensions, and mortality and cardiac edema were monitored over 96 h. Survival and cardiotoxicity were assessed and correlated with whole-genome data and clinical outcomes.</div></div><div><h3>Results</h3><div>Two strains exhibited distinct pathogenic effects: HC48 (ST42) caused significantly increased mortality (p < 0.0001), and HC132 (ST669) induced cardiotoxicity in 20 % of embryos. Surprisingly, the hypervirulent control strain NAP1/027 did not produce enhanced virulence in this model.</div></div><div><h3>Conclusion</h3><div>While zebrafish embryos showed promise for distinguishing strain-specific virulence, limitations such as colonization capacity and host–microbe interactions suggest that further research is needed to validate this model for <em>C. difficile</em> virulence testing.</div></div>","PeriodicalId":8050,"journal":{"name":"Anaerobe","volume":"96 ","pages":"Article 102996"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
To assess the microbiological profile of chronic otitis media (COM)-squamosal disease with special reference to anaerobic bacteria, evaluate associations with clinical features, and determine antibiotic susceptibility of anaerobic isolates.
Methods
A prospective observational study was conducted over one year at JIPMER, Puducherry, including 60 patients diagnosed with COM-squamosal disease. Intraoperative ear discharge samples were cultured using aerobic and anaerobic techniques. Bacterial isolates were identified by MALDI-TOF-MS, and anaerobes were confirmed by aerotolerance testing. Antibiotic susceptibility was performed according to EUCAST v.15 2025 guidelines.
Results
Positive cultures were obtained in 76.6 % of cases; aerobes were isolated in 95.6 %, anaerobes in 21.7 %, and fungi in 4.3 %. Polymicrobial/Mixed growth infections were observed in 45.6 % of culture-positive specimens. The predominant aerobic isolate was Pseudomonas aeruginosa, while anaerobic isolates included Bacteroides fragilis, Finegoldia magna, and Peptoniphilus asaccharolyticus. Anaerobic isolates were largely susceptible to metronidazole and carbapenems, with variable resistance patterns.
Conclusion
Anaerobic bacteria significantly contribute to COM-squamosal infections but are often overlooked. Routine anaerobic culture and sensitivity testing should be incorporated into diagnostic protocols to guide effective antimicrobial therapy and prevent complications.
{"title":"Clinical and microbiological profile of patients with chronic otitis media - Squamosal disease with special reference to anaerobes","authors":"Parveez Musharaf , Sangitha Jayagandan , Rakhi Biswas , Kalaiarasi Raja","doi":"10.1016/j.anaerobe.2025.103010","DOIUrl":"10.1016/j.anaerobe.2025.103010","url":null,"abstract":"<div><h3>Objectives</h3><div>To assess the microbiological profile of chronic otitis media (COM)-squamosal disease with special reference to anaerobic bacteria, evaluate associations with clinical features, and determine antibiotic susceptibility of anaerobic isolates.</div></div><div><h3>Methods</h3><div>A prospective observational study was conducted over one year at JIPMER, Puducherry, including 60 patients diagnosed with COM-squamosal disease. Intraoperative ear discharge samples were cultured using aerobic and anaerobic techniques. Bacterial isolates were identified by MALDI-TOF-MS, and anaerobes were confirmed by aerotolerance testing. Antibiotic susceptibility was performed according to EUCAST v.15 2025 guidelines.</div></div><div><h3>Results</h3><div>Positive cultures were obtained in 76.6 % of cases; aerobes were isolated in 95.6 %, anaerobes in 21.7 %, and fungi in 4.3 %. Polymicrobial/Mixed growth infections were observed in 45.6 % of culture-positive specimens. The predominant aerobic isolate was <em>Pseudomonas aeruginosa</em>, while anaerobic isolates included <em>Bacteroides fragilis</em>, <em>Finegoldia magna</em>, and <em>Peptoniphilus asaccharolyticus</em>. Anaerobic isolates were largely susceptible to metronidazole and carbapenems, with variable resistance patterns.</div></div><div><h3>Conclusion</h3><div>Anaerobic bacteria significantly contribute to COM-squamosal infections but are often overlooked. Routine anaerobic culture and sensitivity testing should be incorporated into diagnostic protocols to guide effective antimicrobial therapy and prevent complications.</div></div>","PeriodicalId":8050,"journal":{"name":"Anaerobe","volume":"96 ","pages":"Article 103010"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145328067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cosmetic products, which typically contain multiple ingredients such as ethanol, glycerol and Tween 80 (polysorbate 80), may influence the homeostasis of the skin microbiome. However, the effect of common ingredients on the anaerobic members of human skin microbiome is poorly studied. In this study, we directly evaluated the effects of common cosmetic ingredients on a dominant human skin anaerobe Cutibacterium acnes using in vitro techniques.
Materials and methods
Five cosmetic ingredients were added to seven C. acnes strains, including type strains of the three subspecies (types I, II, and III), and their effects were evaluated by monitoring growth curves based on turbidity measurements.
Results
All strains exhibited growth inhibition in response to high concentrations (10 % v/v) of ethanol and glycerol, whereas low concentrations (3 % and/or 1 % v/v) of ethanol enhanced bacterial growth. The nonionic detergent Tween 80 significantly enhanced the growth of type I strains, with some strains also producing insoluble precipitates, which may relate to comedogenesis. In contrast, type III strains did not produce precipitates. The two polyamines, putrescine and spermidine, elicited a biphasic response, with growth inhibition observed at higher concentrations and growth promotion at lower concentrations.
Conclusion
The response of C. acnes subspecies/strains to the cosmetic components varied with the different ingredient concentrations, often exhibiting opposite effects.
{"title":"Effects of common cosmetic ingredients on growth of dominant human skin inhabitant Cutibacterium acnes","authors":"Osamu Funatsu , Itaru Dekio , Hiroko Ishii , Reiko Shimatsu , Yutaka Shimokawa , Akihiko Asahina","doi":"10.1016/j.anaerobe.2025.102999","DOIUrl":"10.1016/j.anaerobe.2025.102999","url":null,"abstract":"<div><h3>Objectives</h3><div>Cosmetic products, which typically contain multiple ingredients such as ethanol, glycerol and Tween 80 (polysorbate 80), may influence the homeostasis of the skin microbiome. However, the effect of common ingredients on the anaerobic members of human skin microbiome is poorly studied. In this study, we directly evaluated the effects of common cosmetic ingredients on a dominant human skin anaerobe <em>Cutibacterium acnes</em> using <em>in vitro</em> techniques.</div></div><div><h3>Materials and methods</h3><div>Five cosmetic ingredients were added to seven <em>C</em>. <em>acnes</em> strains, including type strains of the three subspecies (types I, II, and III), and their effects were evaluated by monitoring growth curves based on turbidity measurements.</div></div><div><h3>Results</h3><div>All strains exhibited growth inhibition in response to high concentrations (10 % v/v) of ethanol and glycerol, whereas low concentrations (3 % and/or 1 % v/v) of ethanol enhanced bacterial growth. The nonionic detergent Tween 80 significantly enhanced the growth of type I strains, with some strains also producing insoluble precipitates, which may relate to comedogenesis. In contrast, type III strains did not produce precipitates. The two polyamines, putrescine and spermidine, elicited a biphasic response, with growth inhibition observed at higher concentrations and growth promotion at lower concentrations.</div></div><div><h3>Conclusion</h3><div>The response of <em>C. acnes</em> subspecies/strains to the cosmetic components varied with the different ingredient concentrations, often exhibiting opposite effects.</div></div>","PeriodicalId":8050,"journal":{"name":"Anaerobe","volume":"96 ","pages":"Article 102999"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
To identify risk factors for Clostridioides difficile infection (CDI) in patients with malignant tumours and establish a predictive model for clinical prevention and early intervention.
Methods
This retrospective study included 92 patients with malignant tumours (46 CDI-positive, 46 CDI-negative) admitted to our hospital. Demographic characteristics, clinical parameters, laboratory indicators and treatment factors were collected and analyzed. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for CDI, and a predictive model was established and evaluated using receiver operating characteristic curve analysis.
Results
Patients with CDI had significantly lower serum albumin levels (30.12 ± 5.86 vs 34.15 ± 7.88 g/L, P = 0.007) and higher C-reactive protein (CRP) levels (89.38 ± 91.01 vs 49.17 ± 51.78 mg/L, P = 0.011) than patients without CDI. The CDI-positive group had significantly higher rates of multiple antibiotic use (52.2 % vs 10.9 %, P < 0.001) and corticosteroid/immunosuppressant use (58.7 % vs 30.4 %, P = 0.007) than the CDI-negative group. Multivariate logistic regression analysis identified four independent risk factors for CDI: multiple antibiotic use (odds ratio [OR] = 7.56, 95 % confidence interval [CI]: 2.41–23.73, P < 0.001), corticosteroid/immunosuppressant use (OR = 2.81, 95 % CI: 1.08–7.32, P = 0.035), serum albumin (per g/L increase: OR = 0.94, 95 % CI: 0.88–1.00, P = 0.049) and CRP (per mg/L increase: OR = 1.01, 95 % CI: 1.00–1.01, P = 0.047). The multivariate predictive model demonstrated excellent discriminative ability (area under the curve = 0.907).
Conclusion
Multiple antibiotic use, corticosteroid/immunosuppressant therapy, hypoalbuminaemia and elevated CRP are independent risk factors for CDI in patients with malignant tumours. The predictive model established in this study may help identify patients at high risk who could benefit from preventive interventions.
目的：探讨恶性肿瘤患者艰难梭菌感染（clostridiides difficile， CDI）的危险因素，建立临床预防和早期干预的预测模型。方法：回顾性分析我院收治的92例恶性肿瘤患者（46例cdi阳性，46例cdi阴性）。收集和分析患者的人口学特征、临床参数、实验室指标和治疗因素。采用单因素和多因素logistic回归分析，确定CDI的独立危险因素，建立预测模型并采用受试者工作特征曲线分析进行评价。结果：CDI患者血清白蛋白水平（30.12±5.86 vs 34.15±7.88 g/L, P = 0.007）明显低于无CDI患者，c反应蛋白（CRP）水平（89.38±91.01 vs 49.17±51.78 mg/L, P = 0.011）明显高于无CDI患者。cdi阳性组多种抗生素使用率（52.2% vs 10.9%, P < 0.001）和皮质类固醇/免疫抑制剂使用率（58.7% vs 30.4%, P = 0.007）均显著高于cdi阴性组。多因素logistic回归分析确定了CDI的四个独立危险因素：多种抗生素使用（优势比[OR] = 7.56, 95%可信区间[CI]: 2.41 ~ 23.73, P < 0.001）、皮质类固醇/免疫抑制剂使用（OR = 2.81, 95% CI: 1.08 ~ 7.32, P = 0.035）、血清白蛋白（每g/L增加：OR = 0.94, 95% CI: 0.88 ~ 1.00, P = 0.049）和CRP（每mg/L增加：OR = 1.01, 95% CI: 1.00 ~ 1.01, P = 0.047）。多元预测模型具有良好的判别能力（曲线下面积= 0.907）。结论：多种抗生素使用、皮质类固醇/免疫抑制剂治疗、低白蛋白血症和CRP升高是恶性肿瘤患者CDI的独立危险因素。本研究建立的预测模型可能有助于识别高危患者，哪些患者可以从预防干预中获益。
{"title":"Detection and risk factor analysis of Clostridioides difficile infection in patients with malignant tumours","authors":"Limin Guo , Zhen Zhang , Xianqin Cao , Weihua Guo , Aimin Yue , Yuhou Shen","doi":"10.1016/j.anaerobe.2025.102993","DOIUrl":"10.1016/j.anaerobe.2025.102993","url":null,"abstract":"<div><h3>Objective</h3><div>To identify risk factors for <em>Clostridioides difficile</em> infection (CDI) in patients with malignant tumours and establish a predictive model for clinical prevention and early intervention.</div></div><div><h3>Methods</h3><div>This retrospective study included 92 patients with malignant tumours (46 CDI-positive, 46 CDI-negative) admitted to our hospital. Demographic characteristics, clinical parameters, laboratory indicators and treatment factors were collected and analyzed. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for CDI, and a predictive model was established and evaluated using receiver operating characteristic curve analysis.</div></div><div><h3>Results</h3><div>Patients with CDI had significantly lower serum albumin levels (30.12 ± 5.86 vs 34.15 ± 7.88 g/L, P = 0.007) and higher C-reactive protein (CRP) levels (89.38 ± 91.01 vs 49.17 ± 51.78 mg/L, P = 0.011) than patients without CDI. The CDI-positive group had significantly higher rates of multiple antibiotic use (52.2 % vs 10.9 %, P < 0.001) and corticosteroid/immunosuppressant use (58.7 % vs 30.4 %, P = 0.007) than the CDI-negative group. Multivariate logistic regression analysis identified four independent risk factors for CDI: multiple antibiotic use (odds ratio [OR] = 7.56, 95 % confidence interval [CI]: 2.41–23.73, P < 0.001), corticosteroid/immunosuppressant use (OR = 2.81, 95 % CI: 1.08–7.32, P = 0.035), serum albumin (per g/L increase: OR = 0.94, 95 % CI: 0.88–1.00, P = 0.049) and CRP (per mg/L increase: OR = 1.01, 95 % CI: 1.00–1.01, P = 0.047). The multivariate predictive model demonstrated excellent discriminative ability (area under the curve = 0.907).</div></div><div><h3>Conclusion</h3><div>Multiple antibiotic use, corticosteroid/immunosuppressant therapy, hypoalbuminaemia and elevated CRP are independent risk factors for CDI in patients with malignant tumours. The predictive model established in this study may help identify patients at high risk who could benefit from preventive interventions.</div></div>","PeriodicalId":8050,"journal":{"name":"Anaerobe","volume":"96 ","pages":"Article 102993"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Taxonomy for clinicians – recent changes in names of anaerobic species with pathogenic or probiotic properties","authors":"Lyudmila Boyanova, Raina Gergova, Rumyana Markovska","doi":"10.1016/j.anaerobe.2025.103002","DOIUrl":"10.1016/j.anaerobe.2025.103002","url":null,"abstract":"","PeriodicalId":8050,"journal":{"name":"Anaerobe","volume":"96 ","pages":"Article 103002"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-10-14DOI: 10.1016/j.anaerobe.2025.103007
Jucy Gabriel , Eleanor Keil , Sanath Chandramouli , Faiza Khondokar , Rachel Wilkinson , Jennifer Trannguyen , Senu Apewokin , Anushri Shankar , Shinsmon Jose
Objectives
Clostridioides difficile infection (CDI) is a significant healthcare burden, characterized by severe colitis and high recurrence rates. Although neutrophils migrate rapidly to the colon infected with C. difficile, it does not lead to pathogen clearance. Understanding how pathogen survives within the host remains a knowledge gap. This study investigates host-pathogen interactions in controlled in vitro settings.
Methods
Multiple strains of C. difficile (M7404, VPI10463, R20291, and clinical isolates) were co-cultured with neutrophils, macrophages, and intestinal epithelial cells (IECs) under anaerobic conditions, and bacterial growth was assessed by optical density and micro-replicator-mediated colony assays. Microbial transcriptomics and pathway enrichment analyses were performed 18 h after M7404-neutrophil coculture to understand the metabolic adaptations.
Results
Neutrophils significantly accelerated the growth of C. difficile in anaerobic co-culture. Transcriptomic analysis revealed extensive metabolic reprogramming in C. difficile, including upregulation of oxidative phosphorylation, carbon fixation, and fermentation pathways, suggesting that the bacterium exploits host-derived nutrients to its advantage. Further highlighting the microbial metabolic switch towards utilizing host-derived nutrients, we observed the upregulation of glycerol kinase and the ethanolamine utilization protein. The downregulation of TCA cycle enzymes and upregulation of catalases suggested a shift away from oxidative metabolism and an effort to mitigate neutrophil-induced stress. C. difficile bacterium underwent similar transcriptional programming in coculture with macrophages and IECs.
Conclusions
The transcriptional regulation of C. difficile metabolic genes in the presence of mammalian cells reveals a key virulence trait that enables pathogen persistence within a host. This study also highlights a paradoxical role of neutrophils in CDI, where it's presence may inadvertently enhance pathogen survival. Targeting these metabolic interactions could lead to novel therapeutic strategies for mitigating CDI severity.
{"title":"Metabolic plasticity enables Clostridioides difficile growth in coculture with neutrophils and other mammalian cells","authors":"Jucy Gabriel , Eleanor Keil , Sanath Chandramouli , Faiza Khondokar , Rachel Wilkinson , Jennifer Trannguyen , Senu Apewokin , Anushri Shankar , Shinsmon Jose","doi":"10.1016/j.anaerobe.2025.103007","DOIUrl":"10.1016/j.anaerobe.2025.103007","url":null,"abstract":"<div><h3>Objectives</h3><div><em>Clostridioides difficile</em> infection (CDI) is a significant healthcare burden, characterized by severe colitis and high recurrence rates. Although neutrophils migrate rapidly to the colon infected with <em>C. difficile</em>, it does not lead to pathogen clearance. Understanding how pathogen survives within the host remains a knowledge gap. This study investigates host-pathogen interactions in controlled <em>in vitro</em> settings.</div></div><div><h3>Methods</h3><div>Multiple strains of <em>C. difficile</em> (M7404, VPI10463, R20291, and clinical isolates) were co-cultured with neutrophils, macrophages, and intestinal epithelial cells (IECs) under anaerobic conditions, and bacterial growth was assessed by optical density and micro-replicator-mediated colony assays. Microbial transcriptomics and pathway enrichment analyses were performed 18 h after M7404-neutrophil coculture to understand the metabolic adaptations.</div></div><div><h3>Results</h3><div>Neutrophils significantly accelerated the growth of <em>C. difficile</em> in anaerobic co-culture. Transcriptomic analysis revealed extensive metabolic reprogramming in <em>C. difficile</em>, including upregulation of oxidative phosphorylation, carbon fixation, and fermentation pathways, suggesting that the bacterium exploits host-derived nutrients to its advantage. Further highlighting the microbial metabolic switch towards utilizing host-derived nutrients, we observed the upregulation of glycerol kinase and the ethanolamine utilization protein. The downregulation of TCA cycle enzymes and upregulation of catalases suggested a shift away from oxidative metabolism and an effort to mitigate neutrophil-induced stress. <em>C. difficile</em> bacterium underwent similar transcriptional programming in coculture with macrophages and IECs.</div></div><div><h3>Conclusions</h3><div>The transcriptional regulation of <em>C. difficile</em> metabolic genes in the presence of mammalian cells reveals a key virulence trait that enables pathogen persistence within a host. This study also highlights a paradoxical role of neutrophils in CDI, where it's presence may inadvertently enhance pathogen survival. Targeting these metabolic interactions could lead to novel therapeutic strategies for mitigating CDI severity.</div></div>","PeriodicalId":8050,"journal":{"name":"Anaerobe","volume":"96 ","pages":"Article 103007"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-10-18DOI: 10.1016/j.anaerobe.2025.103006
Rohan Mishra , Adam Harvey , Amy Guo , Glenn Tillotson , Paul Feuerstadt , Sahil Khanna , William D. Shannon , Ken F. Blount
Objectives
Increasing evidence indicates a gut microbiome-brain axis, but more robust statistical methods are needed to solidify this connection. In a large phase 3, randomized, placebo-controlled clinical trial (PUNCH CD3; NCT03244644), fecal microbiota, live-jslm (REBYOTA; RBL, previously RBX2660), was effective in preventing recurrent Clostridium difficile infections, and trial participants had significant gut microbiome and metabolome shifts concurrent with significant changes in health-related quality of life (HRQOL). Advanced statistical methods were applied to data from this trial to further explore and demonstrate associations between changing HRQOL and microbiome or metabolome changes.
Methods
A categorical statistical analysis queried whether patient-reported Cdiff32 HRQOL scores were more likely to improve after RBL than after placebo among PUNCH CD3 participants, and a Dirichlet-multinominal recursive partitioning model assessed whether mental domain Cdiff32 HRQOL scores were linked to participants’ fecal microbiome or bile acid compositions.
Results
Cdiff32 mental domain HRQOL scores were more likely to be improved after RBL administration compared with placebo among treatment responders. Cdiff32 mental domain scores were associated with changing gut microbiome and metabolome compositions, with a gradient of increased Clostridia and Bacteroidia and increased secondary bile acid predominance associated with better Cdiff32 scores.
Conclusions
The microbiota-gut-brain axis is posited to modulate health-related quality of life, microbiome, and metabolome changes through immune, gastrointestinal, and central nervous system functions in patients with recurrent C. difficile infection following RBL administration. These analyses provide a novel approach for investigating multi-omics data and categorical health-related quality of life questionnaires and generate new insights for further clinical studies.
{"title":"Microbiome and metabolome changes after fecal microbiota, live-jslm, administration are associated with health-related quality of life improvements","authors":"Rohan Mishra , Adam Harvey , Amy Guo , Glenn Tillotson , Paul Feuerstadt , Sahil Khanna , William D. Shannon , Ken F. Blount","doi":"10.1016/j.anaerobe.2025.103006","DOIUrl":"10.1016/j.anaerobe.2025.103006","url":null,"abstract":"<div><h3>Objectives</h3><div>Increasing evidence indicates a gut microbiome-brain axis, but more robust statistical methods are needed to solidify this connection. In a large phase 3, randomized, placebo-controlled clinical trial (PUNCH CD3; NCT03244644), fecal microbiota, live-jslm (REBYOTA; RBL, previously RBX2660), was effective in preventing recurrent <em>Clostridium difficile</em> infections, and trial participants had significant gut microbiome and metabolome shifts concurrent with significant changes in health-related quality of life (HRQOL). Advanced statistical methods were applied to data from this trial to further explore and demonstrate associations between changing HRQOL and microbiome or metabolome changes.</div></div><div><h3>Methods</h3><div>A categorical statistical analysis queried whether patient-reported Cdiff32 HRQOL scores were more likely to improve after RBL than after placebo among PUNCH CD3 participants, and a Dirichlet-multinominal recursive partitioning model assessed whether mental domain Cdiff32 HRQOL scores were linked to participants’ fecal microbiome or bile acid compositions.</div></div><div><h3>Results</h3><div>Cdiff32 mental domain HRQOL scores were more likely to be improved after RBL administration compared with placebo among treatment responders. Cdiff32 mental domain scores were associated with changing gut microbiome and metabolome compositions, with a gradient of increased Clostridia and Bacteroidia and increased secondary bile acid predominance associated with better Cdiff32 scores.</div></div><div><h3>Conclusions</h3><div>The microbiota-gut-brain axis is posited to modulate health-related quality of life, microbiome, and metabolome changes through immune, gastrointestinal, and central nervous system functions in patients with recurrent <em>C. difficile</em> infection following RBL administration. These analyses provide a novel approach for investigating multi-omics data and categorical health-related quality of life questionnaires and generate new insights for further clinical studies.</div></div><div><h3>Clinical trial registration</h3><div>NCT03244644.</div></div>","PeriodicalId":8050,"journal":{"name":"Anaerobe","volume":"96 ","pages":"Article 103006"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-11-04DOI: 10.1016/j.anaerobe.2025.103011
Bruce A. McClane , Jihong Li , Francisco A. Uzal , Julian I. Rood
Clostridium perfringens is an important human and veterinary pathogen, as well as a common member of the normal intestinal microbiota. By applying molecular approaches, substantial progress has been achieved since 1995 in understanding the pathogenicity and biology of this gram-positive, anaerobic, spore-forming bacterium. For example, there is now a much improved understanding of the structure and action of its “legacy” toxins (i.e., CPA, PFO, ETX, CPB, ITX and CPE) and the pathogenic importance of many of those toxins has now been clearly demonstrated. In addition, several new toxins have been discovered since 1995 and at least one of those new toxins (NetB) has been clearly linked to disease. The importance and diversity of mobile genetic elements, particularly conjugative plasmids, for pathogenicity and antibiotic resistance is now established. Several regulators controlling virulence gene expression have been identified and, in some cases, their regulatory mechanisms have been clarified. For some regulators, their importance for virulence has also been demonstrated. Lastly, there is also improved knowledge of sporulation and germination mechanisms for C. perfringens, as well as how sporulation contributes to disease transmission and pathogenesis for this bacterium. Despite these advances, some important questions about C. perfringens remain to be explored.
{"title":"Milestones in Clostridium perfringens research since 1995","authors":"Bruce A. McClane , Jihong Li , Francisco A. Uzal , Julian I. Rood","doi":"10.1016/j.anaerobe.2025.103011","DOIUrl":"10.1016/j.anaerobe.2025.103011","url":null,"abstract":"<div><div><em>Clostridium perfrin</em>gens is an important human and veterinary pathogen, as well as a common member of the normal intestinal microbiota. By applying molecular approaches, substantial progress has been achieved since 1995 in understanding the pathogenicity and biology of this gram-positive, anaerobic, spore-forming bacterium. For example, there is now a much improved understanding of the structure and action of its “legacy” toxins (i.e., CPA, PFO, ETX, CPB, ITX and CPE) and the pathogenic importance of many of those toxins has now been clearly demonstrated. In addition, several new toxins have been discovered since 1995 and at least one of those new toxins (NetB) has been clearly linked to disease. The importance and diversity of mobile genetic elements, particularly conjugative plasmids, for pathogenicity and antibiotic resistance is now established. Several regulators controlling virulence gene expression have been identified and, in some cases, their regulatory mechanisms have been clarified. For some regulators, their importance for virulence has also been demonstrated. Lastly, there is also improved knowledge of sporulation and germination mechanisms for <em>C. perfringens</em>, as well as how sporulation contributes to disease transmission and pathogenesis for this bacterium. Despite these advances, some important questions about <em>C. perfringens</em> remain to be explored.</div></div>","PeriodicalId":8050,"journal":{"name":"Anaerobe","volume":"96 ","pages":"Article 103011"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145457051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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