Gut Microbes最新文献

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Machine-learning assisted discovery unveils novel interplay between gut microbiota and host metabolic disturbance in diabetic kidney disease. 机器学习辅助发现揭示了糖尿病肾病中肠道微生物群与宿主代谢紊乱之间的新型相互作用。
IF 12.2 1区 医学
Gut Microbes Pub Date : 2025-12-01 Epub Date: 2025-03-06 DOI: 10.1080/19490976.2025.2473506
I-Wen Wu, Yu-Chieh Liao, Tsung-Hsien Tsai, Chieh-Hua Lin, Zhao-Qing Shen, Yun-Hsuan Chan, Chih-Wei Tu, Yi-Ju Chou, Chi-Jen Lo, Chi-Hsiao Yeh, Chun-Yu Chen, Heng-Chih Pan, Heng-Jung Hsu, Chin-Chan Lee, Mei-Ling Cheng, Wayne Huey-Herng Sheu, Chi-Chun Lai, Huey-Kang Sytwu, Ting-Fen Tsai
{"title":"Machine-learning assisted discovery unveils novel interplay between gut microbiota and host metabolic disturbance in diabetic kidney disease.","authors":"I-Wen Wu, Yu-Chieh Liao, Tsung-Hsien Tsai, Chieh-Hua Lin, Zhao-Qing Shen, Yun-Hsuan Chan, Chih-Wei Tu, Yi-Ju Chou, Chi-Jen Lo, Chi-Hsiao Yeh, Chun-Yu Chen, Heng-Chih Pan, Heng-Jung Hsu, Chin-Chan Lee, Mei-Ling Cheng, Wayne Huey-Herng Sheu, Chi-Chun Lai, Huey-Kang Sytwu, Ting-Fen Tsai","doi":"10.1080/19490976.2025.2473506","DOIUrl":"10.1080/19490976.2025.2473506","url":null,"abstract":"<p><p>Diabetic kidney disease (DKD) is a serious healthcare dilemma. Nonetheless, the interplay between the functional capacity of gut microbiota and their host remains elusive for DKD. This study aims to elucidate the functional capability of gut microbiota to affect kidney function of DKD patients. A total of 990 subjects were enrolled consisting of a control group (<i>n</i> = 455), a type 2 diabetes mellitus group (DM, <i>n</i> = 204), a DKD group (<i>n</i> = 182) and a chronic kidney disease group (CKD, <i>n</i> = 149). Full-length sequencing of 16S rRNA genes from stool DNA was conducted. Three findings are pinpointed. Firstly, new types of microbiota biomarkers have been created using a machine-learning (ML) method, namely relative abundance of a microbe, presence or absence of a microbe, and the hierarchy ratio between two different taxonomies. Four different panels of features were selected to be analyzed: (i) DM <i>vs</i>. Control, (ii) DKD <i>vs</i>. DM, (iii) DKD <i>vs</i>. CKD, and (iv) CKD <i>vs</i>. Control. These had accuracy rates between 0.72 and 0.78 and areas under curve between 0.79 and 0.86. Secondly, 13 gut microbiota biomarkers, which are strongly correlated with anthropometric, metabolic and/or renal indexes, concomitantly identified by the ML algorithm and the differential abundance method were highly discriminatory. Finally, the predicted functional capability of a DKD-specific biomarker, <i>Gemmiger</i> spp. is enriched in carbohydrate metabolism and branched-chain amino acid (BCAA) biosynthesis. Coincidentally, the circulating levels of various BCAAs (L-valine, L-leucine and L-isoleucine) and their precursor, L-glutamate, are significantly increased in DM and DKD patients, which suggests that, when hyperglycemia is present, there has been alterations in various interconnected pathways associated with glycolysis, pyruvate fermentation and BCAA biosynthesis. Our findings demonstrate that there is a link involving the gut-kidney axis in DKD patients. Furthermore, our findings highlight specific gut bacteria that can acts as useful biomarkers; these could have mechanistic and diagnostic implications.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2473506"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Uncovering de novo polyamine biosynthesis in the gut microbiome and its alteration in inflammatory bowel disease. 揭示肠道微生物组中从头多胺生物合成及其在炎症性肠病中的改变。
IF 12.2 1区 医学
Gut Microbes Pub Date : 2025-12-01 Epub Date: 2025-02-09 DOI: 10.1080/19490976.2025.2464225
Xinwei Li, Xia Xiao, Shengnan Wang, Biyu Wu, Yixuan Zhou, Pan Deng
{"title":"Uncovering <i>de novo</i> polyamine biosynthesis in the gut microbiome and its alteration in inflammatory bowel disease.","authors":"Xinwei Li, Xia Xiao, Shengnan Wang, Biyu Wu, Yixuan Zhou, Pan Deng","doi":"10.1080/19490976.2025.2464225","DOIUrl":"10.1080/19490976.2025.2464225","url":null,"abstract":"<p><p>Polyamines are important gut microbial metabolites known to affect host physiology, yet the mechanisms behind their microbial production remain incompletely understood. In this study, we developed a stable isotope-resolved metabolomic (SIRM) approach to track polyamine biosynthesis in the gut microbiome. Viable microbial cells were extracted from fresh human and mouse feces and incubated anaerobically with [U-<sup>13</sup>C]-labeled inulin (tracer). Liquid chromatography-high resolution mass spectrometry analysis revealed distinct <sup>13</sup>C enrichment profiles for spermidine (SPD) and putrescine (PUT), indicating that the arginine-agmatine-SPD pathway contributes to SPD biosynthesis in addition to the well-known spermidine synthase pathway (PUT aminopropylation). Species differences were observed in the <sup>13</sup>C enrichments of polyamines and related metabolites between the human and mouse microbiome. By analyzing the fecal metabolomics and metatranscriptomic data from an inflammatory bowel disease (IBD) cohort, we found significantly higher polyamine levels in IBD patients compared to healthy controls. Further investigations using single-strain SIRM and <i>in silico</i> analyses identified <i>Bacteroides</i> spp. as key contributors to polyamine biosynthesis, harboring essential genes for this process and potentially driving the upregulation of polyamines in IBD. Taken together, this study expands our understanding of polyamine biosynthesis in the gut microbiome and will facilitate the development of precision therapies to target polyamine-associated diseases.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2464225"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11812404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction. 修正。
IF 12.2 1区 医学
Gut Microbes Pub Date : 2025-12-01 Epub Date: 2025-01-24 DOI: 10.1080/19490976.2025.2457204
{"title":"Correction.","authors":"","doi":"10.1080/19490976.2025.2457204","DOIUrl":"10.1080/19490976.2025.2457204","url":null,"abstract":"","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2457204"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11776457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Life-course socioeconomic position and the gut microbiome in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). 西班牙裔社区健康研究/拉丁裔研究(HCHS/SOL)中的生命过程社会经济地位和肠道微生物组
IF 12.2 1区 医学
Gut Microbes Pub Date : 2025-12-01 Epub Date: 2025-03-18 DOI: 10.1080/19490976.2025.2479772
Monica A Batalha, Madison N LeCroy, Juan Lin, Brandilyn A Peters, Qibin Qi, Zheng Wang, Tao Wang, Linda C Gallo, Gregory A Talavera, Amanda C McClain, Bharat Thyagarajan, Martha L Daviglus, Lifang Hou, Maria Llabre, Jianwen Cai, Robert C Kaplan, Carmen R Isasi
{"title":"Life-course socioeconomic position and the gut microbiome in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).","authors":"Monica A Batalha, Madison N LeCroy, Juan Lin, Brandilyn A Peters, Qibin Qi, Zheng Wang, Tao Wang, Linda C Gallo, Gregory A Talavera, Amanda C McClain, Bharat Thyagarajan, Martha L Daviglus, Lifang Hou, Maria Llabre, Jianwen Cai, Robert C Kaplan, Carmen R Isasi","doi":"10.1080/19490976.2025.2479772","DOIUrl":"10.1080/19490976.2025.2479772","url":null,"abstract":"<p><p>Socioeconomic position (SEP) in childhood and beyond may influence the gut microbiome, with implications for disease risk. Studies evaluating the relationship between life-course SEP and the gut microbiome are sparse, particularly among Hispanic/Latino individuals, who have a high prevalence of low SEP. We use the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a population-based cohort study conducted in four field centers in the United States (U.S.), to evaluate the association between life-course SEP and gut microbiome composition. Life-course SEP indicators included parental education (proxy of childhood SEP), current SEP (<i>n</i> = 2174), and childhood (<i>n</i> = 988) and current economic hardship (<i>n</i> = 994). Shotgun sequencing was performed on stool samples. Analysis of Compositions of Microbiomes was used to identify associations of life-course SEP indicators with gut microbiome species and functions. Parental education and current SEP were associated with the overall gut microbiome composition; however, parental education and current education explained more the gut microbiome variance than the current SEP. A lower parental education and current SEP were associated with a lower abundance of species from genus <i>Bacteroides</i>. In stratified analysis by nativity, we found similar findings mainly among foreign-born participants. Early-life SEP may have long-term effects on gut microbiome composition underscoring another biological mechanism linking early childhood factors to adult disease.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2479772"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
3'-Sialyllactose and B. infantis synergistically alleviate gut inflammation and barrier dysfunction by enriching cross-feeding bacteria for short-chain fatty acid biosynthesis. 3'-唾液基乳糖和B.婴儿通过丰富交叉饲养细菌的短链脂肪酸生物合成,协同缓解肠道炎症和屏障功能障碍。
IF 12.2 1区 医学
Gut Microbes Pub Date : 2025-12-01 Epub Date: 2025-04-07 DOI: 10.1080/19490976.2025.2486512
Mingzhi Yang, Zipeng Jiang, Lutong Zhou, Nana Chen, Huan He, Wentao Li, Zhixin Yu, Siming Jiao, Deguang Song, Yizhen Wang, Mingliang Jin, Zeqing Lu
{"title":"3'-Sialyllactose and <i>B. infantis</i> synergistically alleviate gut inflammation and barrier dysfunction by enriching cross-feeding bacteria for short-chain fatty acid biosynthesis.","authors":"Mingzhi Yang, Zipeng Jiang, Lutong Zhou, Nana Chen, Huan He, Wentao Li, Zhixin Yu, Siming Jiao, Deguang Song, Yizhen Wang, Mingliang Jin, Zeqing Lu","doi":"10.1080/19490976.2025.2486512","DOIUrl":"10.1080/19490976.2025.2486512","url":null,"abstract":"<p><p>Ulcerative colitis (UC) poses significant threats to human health and quality of life worldwide, as it is a chronic inflammatory bowel disease. 3'-sialyllactose (3'-SL) is a key functional component of milk oligosaccharides. This study systematically evaluates the prebiotic effects of 3'-SL and its therapeutic potential in combination with <i>Bifidobacterium infantis</i> (<i>B. infantis</i>) for UC. The findings reveal that 3'-SL and <i>B. infantis</i> synergistically mitigate intestinal inflammation and barrier dysfunction by promoting the production of short-chain fatty acids (SCFAs) through cross-feeding mechanisms among gut microbiota. Individually, 3'-SL, <i>B. infantis</i>, and the synbiotic treatment all effectively alleviated UC symptoms, including reduced weight loss, improved disease activity scores, and prevention of colon shortening. Histopathological and immunofluorescence analyses further demonstrated that the synbiotic treatment significantly ameliorated colonic injury, enhanced barrier function, restored goblet cell counts, increased glycoprotein content in crypt goblet cells, and upregulated the expression of tight junction proteins (ZO-1, occludin, and claudin-1). Notably, the synbiotic treatment outperformed the individual components by better restoring gut microbiota balance, elevating SCFA levels, and modulating serum cytokine profiles, thereby reducing inflammation. These findings provide mechanistic insights into the protective effects of the synbiotic and underscore its therapeutic potential for UC and other intestinal inflammatory disorders.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2486512"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11988227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Deep learning-based detection of bacterial swarm motion using a single image. 基于深度学习的单图像细菌群运动检测。
IF 12.2 1区 医学
Gut Microbes Pub Date : 2025-12-01 Epub Date: 2025-05-14 DOI: 10.1080/19490976.2025.2505115
Yuzhu Li, Hao Li, Weijie Chen, Keelan O'Riordan, Neha Mani, Yuxuan Qi, Tairan Liu, Sridhar Mani, Aydogan Ozcan
{"title":"Deep learning-based detection of bacterial swarm motion using a single image.","authors":"Yuzhu Li, Hao Li, Weijie Chen, Keelan O'Riordan, Neha Mani, Yuxuan Qi, Tairan Liu, Sridhar Mani, Aydogan Ozcan","doi":"10.1080/19490976.2025.2505115","DOIUrl":"10.1080/19490976.2025.2505115","url":null,"abstract":"<p><p>Motility is a fundamental characteristic of bacteria. Distinguishing between swarming and swimming, the two principal forms of bacterial movement, holds significant conceptual and clinical relevance. Conventionally, the detection of bacterial swarming involves inoculating samples on an agar surface and observing colony expansion, which is qualitative, time-intensive, and requires additional testing to rule out other motility forms. A recent methodology that differentiates swarming and swimming motility in bacteria using circular confinement offers a rapid approach to detecting swarming. However, it still heavily depends on the observer's expertise, making the process labor-intensive, costly, slow, and susceptible to inevitable human bias. To address these limitations, we developed a deep learning-based swarming classifier that rapidly and autonomously predicts swarming probability using a single blurry image. Compared with traditional video-based, manually processed approaches, our method is particularly suited for high-throughput environments and provides objective, quantitative assessments of swarming probability. The swarming classifier demonstrated in our work was trained on <i>Enterobacter sp</i>. SM3 and showed good performance when blindly tested on new swarming (positive) and swimming (negative) test images of SM3, achieving a sensitivity of 97.44% and a specificity of 100%. Furthermore, this classifier demonstrated robust external generalization capabilities when applied to unseen bacterial species, such as <i>Serratia marcescens</i> DB10 and <i>Citrobacter koseri</i> H6. This competitive performance indicates the potential to adapt our approach for diagnostic applications through portable devices, which would facilitate rapid, objective, on-site screening for bacterial swarming motility, potentially enhancing the early detection and treatment assessment of various diseases, including inflammatory bowel diseases (IBD) and urinary tract infections (UTI).</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2505115"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
L-serine promotes pro-carcinogenic effects of colibactin-producing E. coli. l -丝氨酸促进产生大肠杆菌素的大肠杆菌的致癌作用。
IF 12.2 1区 医学
Gut Microbes Pub Date : 2025-12-01 Epub Date: 2025-06-05 DOI: 10.1080/19490976.2025.2515480
Amandine Devaux, Romain Villéger, Gwenaëlle Roche, Binta Diémé, Michael Rodrigues, Charline Juban, Marie Lagrée, Nicolas Venisse, Cyril Jousse, Nicolas Barnich, Mathilde Bonnet
{"title":"L-serine promotes pro-carcinogenic effects of colibactin-producing <i>E. coli</i>.","authors":"Amandine Devaux, Romain Villéger, Gwenaëlle Roche, Binta Diémé, Michael Rodrigues, Charline Juban, Marie Lagrée, Nicolas Venisse, Cyril Jousse, Nicolas Barnich, Mathilde Bonnet","doi":"10.1080/19490976.2025.2515480","DOIUrl":"10.1080/19490976.2025.2515480","url":null,"abstract":"<p><p>Colonic tissues are abnormally colonized by colibactin-producing <i>Escherichia coli</i> (CoPEC) in colorectal cancer (CRC) patients. CoPECs have been shown to promote colorectal carcinogenesis in several pre-clinical CRC mouse models. Here, we report that CoPEC reprograms the metabolism of colonic epithelial cells in a colibactin-dependent manner, leading to a Warburg-like effect, altered redox homeostasis, and disrupted amino acid metabolism. Among these metabolic modifications, we observed a significant decrease in both extracellular and intracellular serine levels. We found that CoPEC activates the L-serine-utilization operon during gut colonization, maximizing its competitive fitness advantage over a commensal strain. Moreover, an L-serine-depleted diet induces an early and transient decrease in CoPEC colonization of mice gut, associated with decrease of both DNA damages and tumor development. Finally, deletion of the bacterial <i>tdcA</i> gene involved in L-serine operon utilization reduces the competitive fitness of CoPEC, the <i>in vitro</i> adhesion and persistence within the epithelial cells and leads in CRC animal models to reduced carcinogenic activity of the pathobiont. This work highlights the interplay between intestinal microbiota factors, such as CoPEC, and nutritional factors, such as L-serine, in colorectal carcinogenesis.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2515480"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Tips and tricks for gut microbiota investigation using scanning electron microscopy (SEM): going from sample preparation to imaging and landscape analysis. 使用扫描电子显微镜(SEM)调查肠道微生物群的提示和技巧:从样品制备到成像和景观分析。
IF 12.2 1区 医学
Gut Microbes Pub Date : 2025-12-01 Epub Date: 2025-06-09 DOI: 10.1080/19490976.2025.2512016
Meriem Boukili, Omar Zmerli, Florence Fenollar, Sara Bellali, Jacques Bou Khalil
{"title":"Tips and tricks for gut microbiota investigation using scanning electron microscopy (SEM): going from sample preparation to imaging and landscape analysis.","authors":"Meriem Boukili, Omar Zmerli, Florence Fenollar, Sara Bellali, Jacques Bou Khalil","doi":"10.1080/19490976.2025.2512016","DOIUrl":"10.1080/19490976.2025.2512016","url":null,"abstract":"<p><p>The Gut Microbiota (GM) remains a complex microbial ecosystem with many unknown facets despite significant technologic advancement. This study introduces a novel rapid technique using tabletop scanning electron microscopy (SEM) for investigating GM composition, focusing on <i>Clostridioides difficile</i> infection (CDI) as a representative model for dysbiosis-related diseases. Six stool sample preparation protocols were tested on 40 stool samples to develop an optimized SEM protocol. Protocol stability was evaluated after four-month storage. The optimized protocol produced high-resolution micrographs while maintaining sample integrity over time. SEM investigation of GM was done by analyzing ten stool samples (5-control and 5-<i>C. difficile</i> groups), imaged at low and high magnifications. Object detection analysis generated a SEM-based GM components database helping describe and compare microbial diversity variation between the groups. CDI group revealed a reduction in microbial diversity, compared to the controls. Epithelial and red blood cells were more prevalent in CDI group. Statistical analyses of objects proved clear clustering of samples into CDI and control groups. This study pioneers the proof-of-concept for using tabletop SEM to investigate GM components in a dysbiosis-related disease model. This concept emerges as a complementary technique capable of providing deeper insight to describe GM components previously elusive with other methods.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2512016"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The ladder of regulatory stringency and balance: an application to the US FDA's regulation of bacterial live therapeutics. 监管严格和平衡的阶梯:美国FDA对细菌活疗法监管的应用。
IF 12.2 1区 医学
Gut Microbes Pub Date : 2025-12-01 Epub Date: 2025-06-12 DOI: 10.1080/19490976.2025.2517377
Moshe Maor, Hilit Levy Barazany, Ilana Kolodkin-Gal
{"title":"The ladder of regulatory stringency and balance: an application to the US FDA's regulation of bacterial live therapeutics.","authors":"Moshe Maor, Hilit Levy Barazany, Ilana Kolodkin-Gal","doi":"10.1080/19490976.2025.2517377","DOIUrl":"10.1080/19490976.2025.2517377","url":null,"abstract":"<p><p>The three main types of live bacterial therapies - probiotics, fecal/microbiome transplants, and engineered bacterial therapies - hold immense potential to revolutionize medicine. While offering targeted and personalized treatments for various diseases, these therapies also carry risks such as adverse immune reactions, antibiotic resistance, and the potential for unintended consequences. Therefore, developing and deploying these therapies necessitates a robust regulatory framework to protect public health while fostering innovation. In this paper, we propose a novel conceptual tool - the <i>Ladder of Regulatory Stringency and Balance</i>-which can assist in the design of robust regulatory regimes which encompass medicine practices based not only on definitive Randomized Controlled Trials (RCTs), but also on meta-analyses, observational studies, and clinicians experience. Regulatory stringency refers to the strictness of regulations, while regulatory balance concerns the degree of alignment between the regulatory framework governing a technology and the actual risks posed by specific products within that technology. Focusing on the US regulatory environment, we subsequently position the three types of live bacterial therapies on the <i>Ladder</i>. The insight gained from this exercise demonstrates that probiotics are generally positioned at the bottom of the <i>Ladder</i>, corresponding to low-stringency regulation, with a proportionate regulatory balance. However, probiotics intended for high-risk populations are currently subject to low-stringency regulations, resulting in under-regulation. Our analysis also supports the conclusion that fecal microbiota transplants (FMT) for recurrent <i>Clostridium difficile</i> infection should be positioned close to but below the threshold for under regulation by the U.S. Food and Drug Administration (FDA), and we recommend improved donor screening procedures, preservation and processing, storage, and distribution. Our framework can serve as a scale to assess regulatory gaps for live bacterial therapies and to identify potential solutions where such gaps exist.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2517377"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Fecal gut microbiota and amino acids as noninvasive diagnostic biomarkers of Pediatric inflammatory bowel disease. 粪便肠道菌群和氨基酸作为儿童炎症性肠病的无创诊断生物标志物。
IF 12.2 1区 医学
Gut Microbes Pub Date : 2025-12-01 Epub Date: 2025-06-12 DOI: 10.1080/19490976.2025.2517828
Eva Vermeer, Jasmijn Z Jagt, Eline M Lap, Eduard A Struys, Andries E Budding, Nanda M Verhoeven-Duif, Marjolein Bosma, Johan E van Limbergen, Bart G P Koot, Robert de Jonge, Marc A Benninga, Animesh Acharjee, Nanne K H de Boer, Tim G J de Meij
{"title":"Fecal gut microbiota and amino acids as noninvasive diagnostic biomarkers of Pediatric inflammatory bowel disease.","authors":"Eva Vermeer, Jasmijn Z Jagt, Eline M Lap, Eduard A Struys, Andries E Budding, Nanda M Verhoeven-Duif, Marjolein Bosma, Johan E van Limbergen, Bart G P Koot, Robert de Jonge, Marc A Benninga, Animesh Acharjee, Nanne K H de Boer, Tim G J de Meij","doi":"10.1080/19490976.2025.2517828","DOIUrl":"10.1080/19490976.2025.2517828","url":null,"abstract":"<p><strong>Background and aims: </strong>Fecal calprotectin (FCP) has limited specificity as diagnostic biomarker of pediatric inflammatory bowel disease (IBD), leading to unnecessary invasive endoscopies. This study aimed to develop and validate a fecal microbiota and amino acid (AA)-based diagnostic model.</p><p><strong>Methods: </strong>Fecal samples from a discovery cohort (<i>de novo</i> IBD and healthy controls [HC]) were used to develop the diagnostic model. This model was applied in a validation cohort (<i>de novo</i> IBD and controls with gastrointestinal symptoms [CGI]). Microbiota and AAs were analyzed using interspace profiling and liquid chromatography-mass spectrometry techniques, respectively. Machine learning techniques were used to build the diagnostic model.</p><p><strong>Results: </strong>In the discovery cohort (58 IBD, 59 hC), two microbial species (<i>Escherichia coli</i> and <i>Alistipes finegoldii</i>) and four AAs (leucine, ornithine, taurine, and alpha-aminoadipic acid [AAD]) combined allowed for discrimination between both subgroups (AUC 0.94, 95% CI [0.89, 0.98]). In the validation cohort (43 IBD, 38 CGI), this panel of six markers could differentiate patients with IBD from CGI with an AUC of 0.84, 95% CI [0.67, 0.95]). Leucine showed the best diagnostic performance (AUC 0.89, 95% CI [0.81, 0.95]).</p><p><strong>Conclusions: </strong>Leucine might serve as adjuvant noninvasive biomarker in the diagnostic work-up of pediatric IBD. Future research should investigate whether the combination of leucine with FCP could improve specificity and may help tailor the course of diagnostics.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2517828"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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