The ISME JournalPub Date : 2025-05-11DOI: 10.1093/ismejo/wraf093
Alex V Carr, Anne E Otwell, Kristopher A Hunt, Yan Chen, James Wilson, José P Faria, Filipe Liu, Janaka N Edirisinghe, Jacob J Valenzuela, Serdar Turkarslan, Lauren M Lui, Torben N Nielsen, Adam P Arkin, Christopher S Henry, Christopher J Petzold, David A Stahl, Nitin S Baliga
{"title":"Emergence and disruption of cooperativity in a denitrifying microbial community","authors":"Alex V Carr, Anne E Otwell, Kristopher A Hunt, Yan Chen, James Wilson, José P Faria, Filipe Liu, Janaka N Edirisinghe, Jacob J Valenzuela, Serdar Turkarslan, Lauren M Lui, Torben N Nielsen, Adam P Arkin, Christopher S Henry, Christopher J Petzold, David A Stahl, Nitin S Baliga","doi":"10.1093/ismejo/wraf093","DOIUrl":"https://doi.org/10.1093/ismejo/wraf093","url":null,"abstract":"Anthropogenic perturbations to the nitrogen cycle, primarily through use of synthetic fertilizers, is driving an unprecedented increase in the emission of nitrous oxide (N2O), a potent greenhouse gas and an ozone depleting substance, causing urgency in identifying the sources and sinks of N2O. Microbial denitrification is a primary contributor to biotic production of N2O in anoxic regions of soil, marine systems, and wastewater treatment facilities. Here, through comprehensive genome analysis, we show that pathway partitioning is a ubiquitous mechanism of complete denitrification within microbial communities. We have investigated mechanisms and consequences of process partitioning of denitrification through detailed physiological characterization and kinetic modeling of a synthetic community of Rhodanobacter thiooxydans FW510-R12 and Acidovorax sp. GW101-3H11. We have discovered that these two bacterial isolates, from a heavily nitrate (NO3−) contaminated superfund site, complete denitrification through the exchange of nitrite (NO2−) and nitric oxide (NO). The process partitioning of denitrification and other processes, including amino acid metabolism, contribute to increased cooperativity within this denitrifying community. We demonstrate that certain contexts, such as high NO3−, cause unbalanced growth of community members, due to differences in their substrate utilization kinetics. The altered growth characteristics of community members drives accumulation of toxic NO2−, which disrupts denitrification causing N2O off gassing.","PeriodicalId":516554,"journal":{"name":"The ISME Journal","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The ISME JournalPub Date : 2025-05-11DOI: 10.1093/ismejo/wraf082
John C Crow, Hao Geng, Christopher J Geiger, Timothy J Sullivan, Shannon M Soucy, Daniel Schultz
{"title":"Drug delivery dynamics dictate evolution of bacterial antibiotic responses","authors":"John C Crow, Hao Geng, Christopher J Geiger, Timothy J Sullivan, Shannon M Soucy, Daniel Schultz","doi":"10.1093/ismejo/wraf082","DOIUrl":"https://doi.org/10.1093/ismejo/wraf082","url":null,"abstract":"Microbes inhabit natural environments that are remarkably dynamic. Therefore, microbes harbor regulated genetic mechanisms to sense shifts in conditions and induce the appropriate responses. Recent studies suggest that the initial evolution of microbes occupying new niches favors mutations in regulatory pathways. However, it is not clear how this evolution is affected by how quickly conditions change (i.e. dynamics), or which mechanisms are commonly used to implement new regulation. Here, we perform experimental evolution on continuous cultures of E. coli carrying the tetracycline resistance tet operon to identify specific mutations that adapt drug responses to different dynamic regimens of drug administration. We find that cultures evolved under gradually increasing tetracycline concentrations show no mutations in the tet operon, but instead a predominance of fine-tuning mutations increasing the affinity of an alternative efflux pump AcrB to tetracycline. When cultures are instead periodically exposed to large drug doses, all populations evolved transposon insertions in repressor TetR, resulting in loss of regulation and constitutive expression of efflux pump TetA. We use a mathematical model of the dynamics of antibiotic responses to show that sudden exposure to large drug concentrations overwhelm regulated responses, which cannot induce resistance fast enough, resulting in selection for constitutive expression of resistance. These results help explain the frequent loss of regulation of antibiotic resistance by pathogens evolved in clinical environments. Our experiment supports the notion that initial evolution in new ecological niches proceeds largely through regulatory mutations and suggests that transposon insertions are a main mechanism driving this process.","PeriodicalId":516554,"journal":{"name":"The ISME Journal","volume":"126 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The ISME JournalPub Date : 2025-05-11DOI: 10.1093/ismejo/wraf091
R Craig MacLean, Cédric Lood, Rachel M Wheatley
{"title":"Chromosomal capture of beneficial genes drives plasmids towards ecological redundancy","authors":"R Craig MacLean, Cédric Lood, Rachel M Wheatley","doi":"10.1093/ismejo/wraf091","DOIUrl":"https://doi.org/10.1093/ismejo/wraf091","url":null,"abstract":"Plasmids are a ubiquitous feature of bacterial genomes, but the forces driving genes and phenotypes to become associated with plasmids are poorly understood. To address this problem, we compared the fitness effects of chromosomal and plasmid genes in the plant symbiont Rhizobium leguminosarum. The relative abundance of beneficial genes on plasmids was very low compared to the chromosome across niches that reflect key steps in plant colonization. Two lines of evidence support the hypothesis that this pattern emerges because evolutionary processes drive beneficial genes to move from plasmids to the bacterial chromosome. First, weakly beneficial genes that increased fitness in a single niche were evenly distributed between plasmids and the chromosome, whereas the chromosome was enriched for strongly beneficial genes that increased fitness multiple niches. Second, beneficial genes were more prevalent on recently acquired plasmids compared to ancient plasmids. Our findings support a model in which bacterial lineages initially acquire plasmids due to the beneficial genes that they carry, but the movement of beneficial genes to the chromosome gradually erodes the ecological value of plasmids. These findings reconcile existing models of plasmids and highlight the challenge of understanding how plasmids can persist over the long term.","PeriodicalId":516554,"journal":{"name":"The ISME Journal","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Beneficial and detrimental fungi within the culturable mycobiome of the Red Sea coral Stylophora pistilatta","authors":"Lior Granit, Rotem Levi, Nofar Lifshitz, Guilhem Banc-Prandi, Einat Zelinger, Britt Ronen, Judith Kraut-Cohen, Ankur Naqib, Stefan J Green, Maoz Fine, Oded Yarden","doi":"10.1093/ismejo/wraf090","DOIUrl":"https://doi.org/10.1093/ismejo/wraf090","url":null,"abstract":"The presence of fungi in the coral microbiome is increasingly recognized, yet their potential impact on the holobiont’s health, particularly under stress conditions, remains underexplored. To address this gap, we isolated over 200 strains (predominantly Ascomycota) from the common scleractinian Red Sea coral, Stylophora pistillata. Using conidia from a rare (Stachybotrys chlorohalonata) and a common (Cladosporium halotolerans) fungal symbiont, we investigated their effects on coral fragments maintained at ambient (25°C) and elevated (33°C) sea temperatures. Inoculation with S. chlorohalonata resulted in significant tissue loss, across both water temperature treatments. Conversely, inoculation with C. halotolerans did not result in visible effects at ambient temperature, but mitigated tissue loss at elevated temperature. This protective effect was accompanied by reduced expression of stress-induced peroxiredoxin-6 and Rad51 host genes, yet not that of Hsp70. Additionally, potential algal symbiont photosynthetic efficiency was higher by over 25% in the elevated temperature treatment, concurrent with higher bacterial diversity, including a marked reduction (>3-fold) in the proliferation of Vibrionaceae in the C. halotolerans-treated coral nubbins. These findings reveal the contrasting impacts of fungal symbionts on coral health, highlighting the dual roles of the mycobiome in influencing holobiont resilience under environmental stress.","PeriodicalId":516554,"journal":{"name":"The ISME Journal","volume":"109 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The ISME JournalPub Date : 2025-05-03DOI: 10.1093/ismejo/wraf062
Yu-Jia Cai, Hong-Yang Zhang, Xiao-Ran Hu, Yu-Chen Yang, Christina Hazard, Graeme W Nicol, Ji-Zheng He, Ju-Pei Shen, Zi-Yang He, Lu Zhang, Jing-Hui Zhang, Hao Liu, Sha Zhang, Zheng Chen
{"title":"Millimeter-scale niche differentiation of N-cycling microorganisms across the soil-water interface has implications for N2O emissions from wetlands","authors":"Yu-Jia Cai, Hong-Yang Zhang, Xiao-Ran Hu, Yu-Chen Yang, Christina Hazard, Graeme W Nicol, Ji-Zheng He, Ju-Pei Shen, Zi-Yang He, Lu Zhang, Jing-Hui Zhang, Hao Liu, Sha Zhang, Zheng Chen","doi":"10.1093/ismejo/wraf062","DOIUrl":"https://doi.org/10.1093/ismejo/wraf062","url":null,"abstract":"Wetlands can be a significant source of N2O under current global climate change regime with the soil-water interface representing a biogeochemical hotspot for microbial activity. However, the role of soil-water interface in controlling N2O emissions remains poorly understood. We hypothesized that the millimeter-scale redox gradient across the soil-water interface generates corresponding distinct niche for N-cycling microorganisms that collectively regulate the production and consumption of N2O over the same spatial scale. The abundance, transcriptional activity and spatial organization of different N-cycling guilds across the soil-water interface were characterized in mesocosms from three different paddy soils with different N2O emissions. Results demonstrated millimeter-scale stratification of N-cycling microbial activity across the soil-water interface, and in particular within the first 10 mm of flooded soils. Ammonia-oxidizing microorganisms were only transcriptionally active in the top 4 mm, suggesting a previously underestimated contribution to N2O emissions from wetlands. Variation in N2O accumulation was observed across the soil-water interface, with the highest concentrations measured at either the soil-water interface or in the deeper anoxic layer of paddy soils. Despite this difference, N2O-reducing microorganisms exhibited high transcriptional activity at the soil-water interface in all soils, suggesting that there is a microbial-mediated sink for N2O across the soil-water interface that can reduce N2O produced from both oxic and anoxic layers. This work demonstrate an underappreciated and essential role of the microbial hot zones at soil-water interface in regulating N2O emissions from wetlands.","PeriodicalId":516554,"journal":{"name":"The ISME Journal","volume":"75 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The ISME JournalPub Date : 2025-05-03DOI: 10.1093/ismejo/wraf081
Emily E Putnam, Robert May, Nina Freeman, Dillon Arrigan, Andrew Boylan, Laura H Childs, Benjamin E Wolfe
{"title":"Fungi shape genome evolution of bacteria even in the absence of major growth phenotypes","authors":"Emily E Putnam, Robert May, Nina Freeman, Dillon Arrigan, Andrew Boylan, Laura H Childs, Benjamin E Wolfe","doi":"10.1093/ismejo/wraf081","DOIUrl":"https://doi.org/10.1093/ismejo/wraf081","url":null,"abstract":"Studies of microbial interactions often emphasize interactions with large, easily measurable growth differences and short-term ecological outcomes spanning just a few generations. However, more subtle interactions, such as those without obvious phenotypes, may play a significant role in shaping both the short-term ecological dynamics and the long-term evolutionary trajectories of microbial species. We used the cheese rind model microbiome to examine how two fungal species, Penicillium camemberti and Geotrichum candidum, impact global gene expression and genome evolution of the bacterium Pseudomonas carnis LP. Even though fungi had limited impacts on the growth of P. carnis LP, approximately 4–40% of its genome was differentially expressed, depending on the specific fungal partner. When we evolved this Pseudomonas strain alone or in co-culture with each of the fungi, we observed frequent mutations in global regulators of nitrogen regulation, secondary metabolite production, and motility, depending on the fungus. Strikingly, many strains with mutations in the nitrogen regulatory gene ntrB emerged when evolved alone or with G. candidum, but not with P. camemberti. Metabolomic and fitness experiments demonstrate that release of free amino acids by P. camemberti removes the fitness advantages conferred by ntrB mutations. Collectively, these results demonstrate that even in the absence of major short-term growth effects, fungi can have substantial impacts on the transcriptome and genomic evolution of bacterial species.","PeriodicalId":516554,"journal":{"name":"The ISME Journal","volume":"75 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The ISME JournalPub Date : 2025-05-01DOI: 10.1093/ismejo/wraf084
Yafang Wang, Xusheng Wang, Zhenhui Chen, Jihua Zheng, Xiangqiang Liu, Yilin Zheng, Zhihao Zheng, Zi Xu, Yaowei Zhang, Keli Chen, Yuqin Zhang, Lu Yu, Yi Ding
{"title":"Akkermansia muciniphila exacerbates acute radiation-induced intestinal injury by depleting mucin and enhancing inflammation","authors":"Yafang Wang, Xusheng Wang, Zhenhui Chen, Jihua Zheng, Xiangqiang Liu, Yilin Zheng, Zhihao Zheng, Zi Xu, Yaowei Zhang, Keli Chen, Yuqin Zhang, Lu Yu, Yi Ding","doi":"10.1093/ismejo/wraf084","DOIUrl":"https://doi.org/10.1093/ismejo/wraf084","url":null,"abstract":"Dysbiosis of gut microbiota plays a crucial role in acute radiation-induced intestinal injury. However, studies on the influence of gut microbiota on acute radiation-induced intestinal injury are inconsistent. In this study, we established an acute radiation-induced intestinal injury mouse model and performed fecal microbiota transplantation to explore the role of the gut microbiota in acute radiation-induced intestinal injury. We observed a significant increase in Akkermansia muciniphila following irradiation, whereas fecal microbiota transplantation effectively reduced Akkermansia muciniphila levels. Contrary to expectations, Akkermansia muciniphila supplementation increased acute radiation-induced intestinal injury and mortality. Mechanistically, post-radiation Akkermansia muciniphila upregulates mucin metabolism genes and consumes mucin, thinning the mucosal barrier and promoting the adhesion and translocation of potential pathogens to epithelial cells, thus exacerbating acute radiation-induced intestinal injury. This enables Akkermansia muciniphila to use mucin as an energy source. Additionally, Akkermansia muciniphila increases the inflammatory macrophage changes and secretion of inflammatory cytokines, leading to a decrease in epithelial stem cell density and inhibition of goblet cell differentiation, further exacerbating acute radiation-induced intestinal injury. Our findings suggest that in certain intestinal environments, the addition of Akkermansia muciniphila may worsen radiation-induced intestinal damage; thus, alternative approaches to reverse the dysbiosis associated with radiotherapy should be explored.","PeriodicalId":516554,"journal":{"name":"The ISME Journal","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The ISME JournalPub Date : 2025-05-01DOI: 10.1093/ismejo/wraf089
Thibaut Morel-Journel, Sonja Lehtinen, Olivier Cotto, Rafika Amia, Sara Dion, Clarisse Figueroa, Jonathan N V Martinson, Pascal Ralaimazava, Olivier Clermont, Xavier Duval, Forough L Nowrouzian, Seth T Walk, Erick Denamur, François Blanquart
{"title":"Residence-colonization trade-off and niche differentiation enable coexistence of Escherichia coli phylogroups in healthy humans","authors":"Thibaut Morel-Journel, Sonja Lehtinen, Olivier Cotto, Rafika Amia, Sara Dion, Clarisse Figueroa, Jonathan N V Martinson, Pascal Ralaimazava, Olivier Clermont, Xavier Duval, Forough L Nowrouzian, Seth T Walk, Erick Denamur, François Blanquart","doi":"10.1093/ismejo/wraf089","DOIUrl":"https://doi.org/10.1093/ismejo/wraf089","url":null,"abstract":"Despite abundant literature on pathogenicity and virulence of the opportunistic pathogen Escherichia coli, much less is known about its ecological and evolutionary dynamics as a commensal. Based on two detailed longitudinal datasets on the gut microbiota of healthy adults followed for months to years in France and the USA, we identified a robust trade-off between the ability to establish in a new host (colonization) and to remain in the host (residence). Major E. coli lineages (phylogroups or subgroups) exhibited similar fitness but diverse strategies, from strong colonisers residing few days in the gut to poor colonisers residing for years. Strains with the largest number of extra-intestinal virulence associated genes and highest pathogenicity also resided for longest in hosts. Furthermore, the residence of a strain was more strongly reduced when it competed with other strains from the same phylogroup than from another phylogroup, suggesting niche differentiation between phylogroups. Based on a discrete-state Markov model developed to describe E. coli dynamics in a host population, we found that the trade-off and niche differentiation acted together as equalizing and stabilizing mechanisms allowing phylogroups to coexist over long periods of time. Our model also predicted that external disturbances may disproportionately affect resident strains, such as the extraintestinal pathogenic ones of subgroup B2.3. Our results call for further studies outside high-income countries, where the prevalence of this phylogroup is much lower. More generally, the trade-off between colonization and persistence could play a role in the diversification of other bacterial species of the microbiome.","PeriodicalId":516554,"journal":{"name":"The ISME Journal","volume":"87 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The ISME JournalPub Date : 2025-05-01DOI: 10.1093/ismejo/wraf087
Brittany D Bennett, David A O Meier, V Celeste Lanclos, Hasti Asrari, John D Coates, J Cameron Thrash
{"title":"Polyhydroxybutyrate production by freshwater SAR11 (LD12)","authors":"Brittany D Bennett, David A O Meier, V Celeste Lanclos, Hasti Asrari, John D Coates, J Cameron Thrash","doi":"10.1093/ismejo/wraf087","DOIUrl":"https://doi.org/10.1093/ismejo/wraf087","url":null,"abstract":"SAR11 bacteria (order Pelagibacterales) are oligotrophs and often the most abundant bacterioplankton in aquatic environments. A subset of sequenced SAR11 genomes, predominantly in the brackish and freshwater SAR11 subclades, contain homologs of pha genes, which in other organisms confer the ability to store carbon and energy via polyhydroxyalkanoate polymers. Here, we investigated the relevance of polyhydroxyalkanoate production to SAR11 biology. Phylogenetics showed that Pha proteins occurred on a long branch and provided evidence for origin at the common ancestor of the brackish IIIa and freshwater LD12 subclades, followed by horizontal transfer within SAR11. Using the LD12 representative “Candidatus Fonsibacter ubiquis” strain LSUCC0530, we found that many LSUCC0530 cells contained a single Nile red-staining granule, confirmed that the cells produced polyhydroxybutyrate, a common form of polyhydroxyalkanoate, and estimated the total polyhydroxybutyrate content in the cells. We heterologously expressed the LSUCC0530 phaCAB locus in Escherichia coli, finding it to be functional and the likely origin of the polyhydroxybutyrate. We also determined that, irrespective of changes to carbon, nitrogen, and phosphorus concentrations, a similar fraction of LSUCC0530 cells generated polyhydroxybutyrate granules and expression of the phaCAB locus remained constant. We suggest that polyhydroxybutyrate synthesis in LSUCC0530 may be constitutively active due to the slow growth dynamics and minimal regulation that characterize SAR11 bacteria. This work characterizes polymer storage in SAR11, providing new insights into the likely fitness advantage for cells harboring this metabolism.","PeriodicalId":516554,"journal":{"name":"The ISME Journal","volume":"70 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The ISME JournalPub Date : 2025-04-30DOI: 10.1093/ismejo/wraf086
Yanan Li,Wen Rui,Xiaoya Sheng,Xilong Deng,Xiaoqian Li,Lingtong Meng,He Huang,Jingpeng Yang
{"title":"Bifidobacterium breve synergizes with Akkermansia muciniphila and Bacteroides ovatus to antagonize Clostridioides difficile.","authors":"Yanan Li,Wen Rui,Xiaoya Sheng,Xilong Deng,Xiaoqian Li,Lingtong Meng,He Huang,Jingpeng Yang","doi":"10.1093/ismejo/wraf086","DOIUrl":"https://doi.org/10.1093/ismejo/wraf086","url":null,"abstract":"The development of ecologically based in vivo microecological formulations for treating Clostridioides difficile infection (CDI) is a current research focus. Here, we selected three microorganisms-Akkermansia muciniphila (AM), Bacteroides ovatus (BO), and Bifidobacterium breve (BB)-to formulate a mixed bacterial formulation (ABB). Subsequently, we evaluated the ecological interactions among these three microorganisms and investigated their therapeutic efficacy in a CDI murine model. Our investigation revealed the presence of a commensalism relationship among AM, BO, and BB. These microorganisms collectively formed a robust and densely packed symbiotic biofilm, with BB being the predominant member in terms of numerical abundance. This phenomenon was concomitant with a marked elevation in the levels of AI-2 and c-di-GMP. ABB exhibits the capability to inhibit crucial biological indicators of C. difficile (CD), such as toxin production, through the secretion of substantial quantities of lactic acid. Additionally, ABB indirectly suppresses CD by activating the NF-κB signaling pathway in Raw 264.7 cells, which stimulates the secretion of significant quantities of IL-6, IL-8, TNF-α, and IL-1β. ABB demonstrated exceptional efficacy in a CDI murine model, as evidenced by a substantial enhancement in survival rates and intestinal short-chain fatty acid (SCFAs) level, the down-regulation of inflammation-associated cytokine secretion, a notable reduction in fecal CD toxin levels, and CD viable bacterial counts. Concurrently, there was an augmentation in the level of gut microbial diversity, accompanied by a rapid reduction in Enterococcus abundance. This ABB formulation holds promise for further development into a novel microecological formulation for the treatment of CDI.","PeriodicalId":516554,"journal":{"name":"The ISME Journal","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}