Pub Date : 2024-09-26DOI: 10.1038/s41522-024-00553-1
Sharareh Tavaddod, Angela Dawson, Rosalind J Allen
Suspended bacterial aggregates play a central role in ocean biogeochemistry, industrial processes and probably many clinical infections - yet the factors that trigger aggregation remain poorly understood, as does the relationship between suspended aggregates and surface-attached biofilms. Here we show that very low doses of cell-wall targeting antibiotic, far below the minimal inhibitory concentration, can trigger aggregation of Escherichia coli cells. This occurs when a few cells lyse, releasing extracellular DNA - thus, cell-to-cell variability in antibiotic response leads to population-level aggregation. Although lysis-triggered aggregation echoes known trigger mechanisms for surface-attached biofilms, these aggregates may have different ecological implications since they do not show increased biofilm-forming potential or increased antibiotic resistance. Our work contributes to understanding the nature of bacterial aggregates and the factors that trigger their formation, and the possible consequences of widespread low-dose antibiotic exposure in the environment and in the body.
悬浮细菌聚集体在海洋生物地球化学、工业生产过程以及许多临床感染中发挥着核心作用,但人们对引发聚集的因素以及悬浮聚集体与表面附着的生物膜之间的关系仍然知之甚少。在这里,我们发现远低于最小抑制浓度的极低剂量细胞壁靶向抗生素就能引发大肠杆菌细胞聚集。当少数细胞裂解,释放出细胞外 DNA 时,就会发生这种情况--因此,细胞与细胞之间对抗生素反应的差异会导致群体聚集。虽然裂解触发的聚集与已知的表面附着生物膜触发机制相呼应,但这些聚集体可能具有不同的生态影响,因为它们并没有显示出更强的生物膜形成潜力或更强的抗生素耐药性。我们的工作有助于了解细菌聚集体的性质、引发其形成的因素,以及在环境和人体中广泛接触低剂量抗生素可能造成的后果。
{"title":"Bacterial aggregation triggered by low-level antibiotic-mediated lysis.","authors":"Sharareh Tavaddod, Angela Dawson, Rosalind J Allen","doi":"10.1038/s41522-024-00553-1","DOIUrl":"https://doi.org/10.1038/s41522-024-00553-1","url":null,"abstract":"<p><p>Suspended bacterial aggregates play a central role in ocean biogeochemistry, industrial processes and probably many clinical infections - yet the factors that trigger aggregation remain poorly understood, as does the relationship between suspended aggregates and surface-attached biofilms. Here we show that very low doses of cell-wall targeting antibiotic, far below the minimal inhibitory concentration, can trigger aggregation of Escherichia coli cells. This occurs when a few cells lyse, releasing extracellular DNA - thus, cell-to-cell variability in antibiotic response leads to population-level aggregation. Although lysis-triggered aggregation echoes known trigger mechanisms for surface-attached biofilms, these aggregates may have different ecological implications since they do not show increased biofilm-forming potential or increased antibiotic resistance. Our work contributes to understanding the nature of bacterial aggregates and the factors that trigger their formation, and the possible consequences of widespread low-dose antibiotic exposure in the environment and in the body.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":"10 1","pages":"90"},"PeriodicalIF":7.8,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11427687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-19DOI: 10.1038/s41522-024-00540-6
Camille Kropp, Kevin Tambosco, Sead Chadi, Philippe Langella, Sandrine P. Claus, Rebeca Martin
Christensenella minuta DSM 22607 has recently been suggested as a potential microbiome-based therapy for inflammatory bowel disease (IBD) because it displays strong anti-inflammatory effects both in vitro and in vivo. Here, we aimed to decipher the mechanism(s) underlying the DSM 22607-mediated beneficial effects on the host in a mouse model of chemically induced acute colitis. We observed that C. minuta plays a key role in the preservation of the epithelial barrier and the management of DNBS-induced inflammation by inhibiting interleukin (IL)-33 and Tumor necrosis factor receptor superfamily member 8 (Tnfrsf8) gene expression. We also showed that DSM 22607 abundance was positively correlated with Akkermansia sp. and Dubosiella sp. and modulated microbial metabolites in the cecum. These results offer new insights into the biological and molecular mechanisms underlying the beneficial effects of C. minuta DSM 22607 by protecting the intestinal barrier integrity and regulating inflammation.
Christensenella minuta DSM 22607最近被认为是一种潜在的基于微生物的炎症性肠病(IBD)疗法,因为它在体外和体内都显示出很强的抗炎作用。在这里,我们的目的是在化学诱导的急性结肠炎小鼠模型中破译 DSM 22607 介导的对宿主有益作用的机制。我们观察到,C. minuta 通过抑制白细胞介素(IL)-33 和肿瘤坏死因子受体超家族成员 8(Tnfrsf8)基因的表达,在保护上皮屏障和控制 DNBS 诱导的炎症中发挥了关键作用。我们还发现,DSM 22607 的丰度与 Akkermansia sp.和 Dubosiella sp.呈正相关,并能调节盲肠中的微生物代谢物。这些结果为我们提供了保护肠道屏障完整性和调节炎症的生物学和分子机制的新见解。
{"title":"Christensenella minuta protects and restores intestinal barrier in a colitis mouse model by regulating inflammation","authors":"Camille Kropp, Kevin Tambosco, Sead Chadi, Philippe Langella, Sandrine P. Claus, Rebeca Martin","doi":"10.1038/s41522-024-00540-6","DOIUrl":"https://doi.org/10.1038/s41522-024-00540-6","url":null,"abstract":"<p><i>Christensenella minuta</i> DSM 22607 has recently been suggested as a potential microbiome-based therapy for inflammatory bowel disease (IBD) because it displays strong anti-inflammatory effects both in vitro and in vivo. Here, we aimed to decipher the mechanism(s) underlying the DSM 22607-mediated beneficial effects on the host in a mouse model of chemically induced acute colitis. We observed that <i>C. minuta</i> plays a key role in the preservation of the epithelial barrier and the management of DNBS-induced inflammation by inhibiting interleukin (IL)-33 and Tumor necrosis factor receptor superfamily member 8 (<i>Tnfrsf8)</i> gene expression. We also showed that DSM 22607 abundance was positively correlated with <i>Akkermansia</i> sp. and <i>Dubosiella</i> sp. and modulated microbial metabolites in the cecum. These results offer new insights into the biological and molecular mechanisms underlying the beneficial effects of <i>C. minuta</i> DSM 22607 by protecting the intestinal barrier integrity and regulating inflammation.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":"54 1","pages":""},"PeriodicalIF":9.2,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-19DOI: 10.1038/s41522-024-00565-x
G. R. van der Ploeg, B. W. Brandt, B. J. F. Keijser, M. H. van der Veen, C. M. C. Volgenant, E. Zaura, A. K. Smilde, J. A. Westerhuis, A. Heintz-Buschart
Gingivitis—the inflammation of the gums—is a reversible stage of periodontal disease. It is caused by dental plaque formation due to poor oral hygiene. However, gingivitis susceptibility involves a complex set of interactions between the oral microbiome, oral metabolome and the host. In this study, we investigated the dynamics of the oral microbiome and its interactions with the salivary metabolome during experimental gingivitis in a cohort of 41 systemically healthy participants. We use Parallel Factor Analysis (PARAFAC), which is a multi-way generalization of Principal Component Analysis (PCA) that can model the variability in the response due to subjects, variables and time. Using the modelled responses, we identified microbial subcommunities with similar dynamics that connect to the magnitude of the gingivitis response. By performing high level integration of the predicted metabolic functions of the microbiome and salivary metabolome, we identified pathways of interest that describe the changing proportions of Gram-positive and Gram-negative microbiota, variation in anaerobic bacteria, biofilm formation and virulence.
{"title":"Multi-way modelling of oral microbial dynamics and host-microbiome interactions during induced gingivitis","authors":"G. R. van der Ploeg, B. W. Brandt, B. J. F. Keijser, M. H. van der Veen, C. M. C. Volgenant, E. Zaura, A. K. Smilde, J. A. Westerhuis, A. Heintz-Buschart","doi":"10.1038/s41522-024-00565-x","DOIUrl":"https://doi.org/10.1038/s41522-024-00565-x","url":null,"abstract":"<p>Gingivitis—the inflammation of the gums—is a reversible stage of periodontal disease. It is caused by dental plaque formation due to poor oral hygiene. However, gingivitis susceptibility involves a complex set of interactions between the oral microbiome, oral metabolome and the host. In this study, we investigated the dynamics of the oral microbiome and its interactions with the salivary metabolome during experimental gingivitis in a cohort of 41 systemically healthy participants. We use Parallel Factor Analysis (PARAFAC), which is a multi-way generalization of Principal Component Analysis (PCA) that can model the variability in the response due to subjects, variables and time. Using the modelled responses, we identified microbial subcommunities with similar dynamics that connect to the magnitude of the gingivitis response. By performing high level integration of the predicted metabolic functions of the microbiome and salivary metabolome, we identified pathways of interest that describe the changing proportions of Gram-positive and Gram-negative microbiota, variation in anaerobic bacteria, biofilm formation and virulence.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":"15 1","pages":""},"PeriodicalIF":9.2,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-17DOI: 10.1038/s41522-024-00559-9
Renfei Wu, Cong Li, Jiuyi Li, Jelmer Sjollema, Gésinda I. Geertsema-Doornbusch, H. Willy de Haan-Visser, Emma S. C. Dijkstra, Yijin Ren, Zexin Zhang, Jian Liu, Hans C. Flemming, Henk J. Busscher, Henny C. van der Mei
Bacteria can be dead, alive, or exhibit slowed or suspended life forms, making bacterial death difficult to establish. Here, agar-plating, microscopic-counting, SYTO9/propidium-iodide staining, MTT-conversion, and bioluminescence-imaging were used to determine bacterial death upon exposure to different conditions. Rank correlations between pairs of assay outcomes were low, indicating different assays measure different aspects of bacterial death. Principal-component analysis yielded two principal components, named “reproductive-ability” (PC1) and “metabolic-activity” (PC2). Plotting of these principal components in two-dimensional space revealed a dead region, with borders defined by the PC1 and PC2 values. Sensu stricto implies an unpractical reality that all assays determining PC1 and PC2 must be carried out in order to establish bacterial death. Considering this unpracticality, it is suggested that at least one assay determining reproductive activity (PC1) and one assay determining metabolic activity (PC2) should be used to establish bacterial death. Minimally, researchers should specifically describe which dimension of bacterial death is assessed, when addressing bacterial death.
{"title":"Bacterial killing and the dimensions of bacterial death","authors":"Renfei Wu, Cong Li, Jiuyi Li, Jelmer Sjollema, Gésinda I. Geertsema-Doornbusch, H. Willy de Haan-Visser, Emma S. C. Dijkstra, Yijin Ren, Zexin Zhang, Jian Liu, Hans C. Flemming, Henk J. Busscher, Henny C. van der Mei","doi":"10.1038/s41522-024-00559-9","DOIUrl":"https://doi.org/10.1038/s41522-024-00559-9","url":null,"abstract":"<p>Bacteria can be dead, alive, or exhibit slowed or suspended life forms, making bacterial death difficult to establish. Here, agar-plating, microscopic-counting, SYTO9/propidium-iodide staining, MTT-conversion, and bioluminescence-imaging were used to determine bacterial death upon exposure to different conditions. Rank correlations between pairs of assay outcomes were low, indicating different assays measure different aspects of bacterial death. Principal-component analysis yielded two principal components, named “reproductive-ability” (PC1) and “metabolic-activity” (PC2). Plotting of these principal components in two-dimensional space revealed a dead region, with borders defined by the PC1 and PC2 values. <i>Sensu stricto</i> implies an unpractical reality that all assays determining PC1 and PC2 must be carried out in order to establish bacterial death. Considering this unpracticality, it is suggested that at least one assay determining reproductive activity (PC1) and one assay determining metabolic activity (PC2) should be used to establish bacterial death. Minimally, researchers should specifically describe which dimension of bacterial death is assessed, when addressing bacterial death.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":"4 1","pages":""},"PeriodicalIF":9.2,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-17DOI: 10.1038/s41522-024-00551-3
Cyril Anjou, Marie Royer, Émilie Bertrand, Marius Bredon, Julie Le Bris, Iria Alonso Salgueiro, Léo C. Caulat, Bruno Dupuy, Frédéric Barbut, Claire Morvan, Nathalie Rolhion, Isabelle Martin-Verstraete
Auranofin (AF), a former rheumatoid polyarthritis treatment, gained renewed interest for its use as an antimicrobial. AF is an inhibitor of thioredoxin reductase (TrxB), a thiol and protein repair enzyme, with an antibacterial activity against several bacteria including C. difficile, an enteropathogen causing post-antibiotic diarrhea. Several studies demonstrated the effect of AF on C. difficile physiology, but the crucial questions of resistance mechanisms and impact on microbiota remain unaddressed. We explored potential resistance mechanisms by studying the impact of TrxB multiplicity and by generating and characterizing adaptive mutations. We showed that if mutants inactivated for trxB genes have a lower MIC of AF, the number of TrxBs naturally present in clinical strains does not impact the MIC. All stable mutations isolated after AF long-term exposure were in the anti-sigma factor of σB and strongly affect physiology. Finally, we showed that AF has less impact on human gut microbiota than vancomycin.
奥拉诺芬(Auranofin,AF)曾是一种治疗类风湿性多关节炎的药物,因其可用作抗菌剂而再次受到关注。AF 是硫氧还原酶(TrxB)的抑制剂,TrxB 是一种硫醇和蛋白质修复酶,对包括艰难梭菌在内的多种细菌具有抗菌活性,艰难梭菌是一种肠道病原体,会引起抗生素后腹泻。一些研究表明了 AF 对艰难梭菌生理机能的影响,但抗药性机制和对微生物群的影响等关键问题仍未得到解决。我们通过研究 TrxB 多样性的影响以及适应性突变的产生和特征,探索了潜在的抗性机制。我们发现,如果 trxB 基因失活的突变体对甲胺磷的 MIC 较低,那么临床菌株中天然存在的 TrxB 数量并不会影响 MIC。长期接触甲胎蛋白后分离到的所有稳定突变都发生在σB的抗σ因子中,并对生理产生强烈影响。最后,我们还发现,与万古霉素相比,甲胎蛋白对人体肠道微生物群的影响较小。
{"title":"Adaptation mechanisms of Clostridioides difficile to auranofin and its impact on human gut microbiota","authors":"Cyril Anjou, Marie Royer, Émilie Bertrand, Marius Bredon, Julie Le Bris, Iria Alonso Salgueiro, Léo C. Caulat, Bruno Dupuy, Frédéric Barbut, Claire Morvan, Nathalie Rolhion, Isabelle Martin-Verstraete","doi":"10.1038/s41522-024-00551-3","DOIUrl":"https://doi.org/10.1038/s41522-024-00551-3","url":null,"abstract":"<p>Auranofin (AF), a former rheumatoid polyarthritis treatment, gained renewed interest for its use as an antimicrobial. AF is an inhibitor of thioredoxin reductase (TrxB), a thiol and protein repair enzyme, with an antibacterial activity against several bacteria including <i>C. difficile</i>, an enteropathogen causing post-antibiotic diarrhea. Several studies demonstrated the effect of AF on <i>C. difficile</i> physiology, but the crucial questions of resistance mechanisms and impact on microbiota remain unaddressed. We explored potential resistance mechanisms by studying the impact of TrxB multiplicity and by generating and characterizing adaptive mutations. We showed that if mutants inactivated for <i>trxB</i> genes have a lower MIC of AF, the number of TrxBs naturally present in clinical strains does not impact the MIC. All stable mutations isolated after AF long-term exposure were in the anti-sigma factor of σ<sup>B</sup> and strongly affect physiology. Finally, we showed that AF has less impact on human gut microbiota than vancomycin.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":"7 1","pages":""},"PeriodicalIF":9.2,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-16DOI: 10.1038/s41522-024-00564-y
Noriaki Oguri, Jun Miyoshi, Yuu Nishinarita, Haruka Wada, Nobuki Nemoto, Noritaka Hibi, Naohiro Kawamura, Sawako Miyoshi, Sonny T. M. Lee, Minoru Matsuura, Takako Osaki, Tadakazu Hisamatsu
Recent evidence indicates that liver cirrhosis (LC) is a reversible condition, but there is no established intervention against liver fibrosis. Although the gut microbiota is considered involved in the pathogenesis of LC, the underlying mechanisms remain unclear. Although the antibiotic, rifaximin (RFX), is effective for hepatic encephalopathy (HE) with LC, the impact of RFX on intestinal bacteria is unknown. We investigated the bacterial compositions along the GI tract under RFX treatment using a murine LC model. RFX improved liver fibrosis and hyperammonemia and altered the bacterial composition in the small intestine. The efficacy of RFX was associated with increases in specific bacterial genera, including Akkermansia. Administration of a commensal strain of Akkermansiamuciniphila improved liver fibrosis and hyperammonemia with changing bacterial composition in the small intestine. This study proposed a new concept “small intestine-liver axis” in the pathophysiology of LC and oral A. muciniphila administration is a promising microbial intervention.
{"title":"Akkermansia muciniphila in the small intestine improves liver fibrosis in a murine liver cirrhosis model","authors":"Noriaki Oguri, Jun Miyoshi, Yuu Nishinarita, Haruka Wada, Nobuki Nemoto, Noritaka Hibi, Naohiro Kawamura, Sawako Miyoshi, Sonny T. M. Lee, Minoru Matsuura, Takako Osaki, Tadakazu Hisamatsu","doi":"10.1038/s41522-024-00564-y","DOIUrl":"https://doi.org/10.1038/s41522-024-00564-y","url":null,"abstract":"<p>Recent evidence indicates that liver cirrhosis (LC) is a reversible condition, but there is no established intervention against liver fibrosis. Although the gut microbiota is considered involved in the pathogenesis of LC, the underlying mechanisms remain unclear. Although the antibiotic, rifaximin (RFX), is effective for hepatic encephalopathy (HE) with LC, the impact of RFX on intestinal bacteria is unknown. We investigated the bacterial compositions along the GI tract under RFX treatment using a murine LC model. RFX improved liver fibrosis and hyperammonemia and altered the bacterial composition in the small intestine. The efficacy of RFX was associated with increases in specific bacterial genera, including <i>Akkermansia</i>. Administration of a commensal strain of <i>Akkermansia</i> <i>muciniphila</i> improved liver fibrosis and hyperammonemia with changing bacterial composition in the small intestine. This study proposed a new concept “small intestine-liver axis” in the pathophysiology of LC and oral <i>A. muciniphila</i> administration is a promising microbial intervention.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":"101 1","pages":""},"PeriodicalIF":9.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142251961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-14DOI: 10.1038/s41522-024-00562-0
Matthew J. Dalby, Raymond Kiu, Iliana R. Serghiou, Asuka Miyazaki, Holly Acford-Palmer, Rathavy Tung, Shabhonam Caim, Sarah Phillips, Magdalena Kujawska, Mitsuaki Matsui, Azusa Iwamoto, Bunsreng Taking, Sharon E. Cox, Lindsay J. Hall
The gut microbiota of infants in low- to middle-income countries is underrepresented in microbiome research. This study explored the faecal microbiota composition and faecal cytokine profiles in a cohort of infants in a rural province of Cambodia and investigated the impact of sample storage conditions and infant environment on microbiota composition. Faecal samples collected at three time points from 32 infants were analysed for microbiota composition using 16S rRNA amplicon sequencing and concentrations of faecal cytokines. Faecal bacterial isolates were subjected to whole genome sequencing and genomic analysis. We compared the effects of two sample collection methods due to the challenges of faecal sample collection in a rural location. Storage of faecal samples in a DNA preservation solution preserved Bacteroides abundance. Microbiota analysis of preserved samples showed that Bifidobacterium was the most abundant genus with Bifidobacterium longum the most abundant species, with higher abundance in breast-fed infants. Most infants had detectable pathogenic taxa, with Shigella and Klebsiella more abundant in infants with recent diarrhoeal illness. Neither antibiotics nor infant growth were associated with gut microbiota composition. Genomic analysis of isolates showed gene clusters encoding the ability to digest human milk oligosaccharides in B. longum and B. breve isolates. Antibiotic-resistant genes were present in both potentially pathogenic species and in Bifidobacterium. Faecal concentrations of Interlukin-1alpha and vascular endothelial growth factor were higher in breast-fed infants. This study provides insights into an underrepresented population of rural Cambodian infants, showing pathogen exposure and breastfeeding impact gut microbiota composition and faecal immune profiles.
中低收入国家婴儿的肠道微生物群在微生物组研究中的代表性不足。本研究探讨了柬埔寨农村省份一组婴儿的粪便微生物群组成和粪便细胞因子谱,并研究了样本储存条件和婴儿环境对微生物群组成的影响。采用 16S rRNA 扩增子测序法对 32 名婴儿在三个时间点采集的粪便样本进行了微生物群组成和粪便细胞因子浓度分析。对粪便细菌分离物进行了全基因组测序和基因组分析。由于在农村地区采集粪便样本存在困难,我们比较了两种样本采集方法的效果。将粪便样本保存在 DNA 保存液中可保持乳杆菌的丰度。对保存样本进行的微生物群分析表明,双歧杆菌是含量最高的菌属,其中长双歧杆菌是含量最高的菌种,母乳喂养婴儿的双歧杆菌含量更高。大多数婴儿都能检测到致病菌类群,近期患腹泻病的婴儿中志贺氏菌和克雷伯氏菌含量更高。抗生素和婴儿生长都与肠道微生物群的组成无关。对分离菌株进行的基因组分析表明,长肠杆菌和布列夫杆菌分离菌株中存在编码消化人乳寡糖能力的基因簇。潜在致病菌和双歧杆菌中都存在抗生素基因。母乳喂养的婴儿粪便中 Interlukin-1alpha 和血管内皮生长因子的浓度较高。这项研究深入了解了柬埔寨农村婴儿这一代表性不足的群体,显示了病原体暴露和母乳喂养对肠道微生物群组成和粪便免疫特征的影响。
{"title":"Faecal microbiota and cytokine profiles of rural Cambodian infants linked to diet and diarrhoeal episodes","authors":"Matthew J. Dalby, Raymond Kiu, Iliana R. Serghiou, Asuka Miyazaki, Holly Acford-Palmer, Rathavy Tung, Shabhonam Caim, Sarah Phillips, Magdalena Kujawska, Mitsuaki Matsui, Azusa Iwamoto, Bunsreng Taking, Sharon E. Cox, Lindsay J. Hall","doi":"10.1038/s41522-024-00562-0","DOIUrl":"https://doi.org/10.1038/s41522-024-00562-0","url":null,"abstract":"<p>The gut microbiota of infants in low- to middle-income countries is underrepresented in microbiome research. This study explored the faecal microbiota composition and faecal cytokine profiles in a cohort of infants in a rural province of Cambodia and investigated the impact of sample storage conditions and infant environment on microbiota composition. Faecal samples collected at three time points from 32 infants were analysed for microbiota composition using 16S rRNA amplicon sequencing and concentrations of faecal cytokines. Faecal bacterial isolates were subjected to whole genome sequencing and genomic analysis. We compared the effects of two sample collection methods due to the challenges of faecal sample collection in a rural location. Storage of faecal samples in a DNA preservation solution preserved <i>Bacteroides</i> abundance. Microbiota analysis of preserved samples showed that <i>Bifidobacterium</i> was the most abundant genus with <i>Bifidobacterium longum</i> the most abundant species, with higher abundance in breast-fed infants. Most infants had detectable pathogenic taxa, with <i>Shigella</i> and <i>Klebsiella</i> more abundant in infants with recent diarrhoeal illness. Neither antibiotics nor infant growth were associated with gut microbiota composition. Genomic analysis of isolates showed gene clusters encoding the ability to digest human milk oligosaccharides in <i>B. longum</i> and <i>B. breve</i> isolates. Antibiotic-resistant genes were present in both potentially pathogenic species and in <i>Bifidobacterium</i>. Faecal concentrations of Interlukin-1alpha and vascular endothelial growth factor were higher in breast-fed infants. This study provides insights into an underrepresented population of rural Cambodian infants, showing pathogen exposure and breastfeeding impact gut microbiota composition and faecal immune profiles.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":"47 1","pages":""},"PeriodicalIF":9.2,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142251962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The role of mast cells (MCs) in ulcerative colitis (UC) development is controversial. FcεRI, the IgE high-affinity receptor, is known to activate MCs. However, its role in UC remains unclear. In our study, Anti-FcεRI showed highly diagnostic value for UC. FcεRIα knockout in mice ameliorated DSS-induced colitis in a gut microbiota-dependent manner. Increased Lactobacillus abundance in FcεRIα deficient mice showed strongly correlation with the remission of colitis. RNA sequencing indicated activation of the NLRP6 inflammasome pathway in FcεRIα knockout mice. Additionally, Lactobacillus plantarum supplementation protected against inflammatory injury and goblet cell loss, with activation of the NLRP6 inflammasome during colitis. Notably, this effect was absent when the strain is unable to produce lactic acid. In summary, colitis was mitigated in FcεRIα deficient mice, which may be attributed to the increased abundance of Lactobacillus. These findings contribute to a better understanding of the relationship between allergic reactions, microbiota, and colitis.
{"title":"Protection against DSS-induced colitis in mice through FcεRIα deficiency: the role of altered Lactobacillus","authors":"Yue Yin, Ruilong Wang, Yanning Li, Wenfei Qin, Letian Pan, Chenyuan Yan, Yusen Hu, Guangqiang Wang, Lianzhong Ai, Qixiang Mei, Li Li","doi":"10.1038/s41522-024-00563-z","DOIUrl":"https://doi.org/10.1038/s41522-024-00563-z","url":null,"abstract":"<p>The role of mast cells (MCs) in ulcerative colitis (UC) development is controversial. FcεRI, the IgE high-affinity receptor, is known to activate MCs. However, its role in UC remains unclear. In our study, Anti-FcεRI showed highly diagnostic value for UC. FcεRIα knockout in mice ameliorated DSS-induced colitis in a gut microbiota-dependent manner. Increased <i>Lactobacillus</i> abundance in FcεRIα deficient mice showed strongly correlation with the remission of colitis. RNA sequencing indicated activation of the NLRP6 inflammasome pathway in FcεRIα knockout mice. Additionally, <i>Lactobacillus plantarum</i> supplementation protected against inflammatory injury and goblet cell loss, with activation of the NLRP6 inflammasome during colitis. Notably, this effect was absent when the strain is unable to produce lactic acid. In summary, colitis was mitigated in FcεRIα deficient mice, which may be attributed to the increased abundance of <i>Lactobacillus</i>. These findings contribute to a better understanding of the relationship between allergic reactions, microbiota, and colitis.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":"20 1","pages":""},"PeriodicalIF":9.2,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142214713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
At present, the diagnosis of lower respiratory tract infections (LRTIs) is difficult, and there is an urgent need for better diagnostic methods. This study enrolled 136 patients from 2020 to 2021 and collected bronchoalveolar lavage fluid (BALF) specimens. We used metatranscriptome to analyze the lower respiratory tract microbiome (LRTM) and host immune response. The diversity of the LRTM in LRTIs significantly decreased, manifested by a decrease in the abundance of normal microbiota and an increase in the abundance of opportunistic pathogens. The upregulated differentially expressed genes (DEGs) in the LRTIs group were mainly enriched in infection immune response-related pathways. Klebsiella pneumoniae had the most significant increase in abundance in LRTIs, which was strongly correlated with host infection or inflammation genes TNFRSF1B, CSF3R, and IL6R. We combined LRTM and host transcriptome data to construct a machine-learning model with 12 screened features to discriminate LRTIs and non-LRTIs. The results showed that the model trained by Random Forest in the validate set had the best performance (ROC AUC: 0.937, 95% CI: 0.832–1). The independent external dataset showed an accuracy of 76.5% for this model. This study suggests that the model integrating LRTM and host transcriptome data can be an effective tool for LRTIs diagnosis.
{"title":"Integrating respiratory microbiome and host immune response through machine learning for respiratory tract infection diagnosis","authors":"Hongbin Chen, Tianqi Qi, Siyu Guo, Xiaoyang Zhang, Minghua Zhan, Si Liu, Yuyao Yin, Yifan Guo, Yawei Zhang, Chunjiang Zhao, Xiaojuan Wang, Hui Wang","doi":"10.1038/s41522-024-00548-y","DOIUrl":"https://doi.org/10.1038/s41522-024-00548-y","url":null,"abstract":"<p>At present, the diagnosis of lower respiratory tract infections (LRTIs) is difficult, and there is an urgent need for better diagnostic methods. This study enrolled 136 patients from 2020 to 2021 and collected bronchoalveolar lavage fluid (BALF) specimens. We used metatranscriptome to analyze the lower respiratory tract microbiome (LRTM) and host immune response. The diversity of the LRTM in LRTIs significantly decreased, manifested by a decrease in the abundance of normal microbiota and an increase in the abundance of opportunistic pathogens. The upregulated differentially expressed genes (DEGs) in the LRTIs group were mainly enriched in infection immune response-related pathways. Klebsiella pneumoniae had the most significant increase in abundance in LRTIs, which was strongly correlated with host infection or inflammation genes TNFRSF1B, CSF3R, and IL6R. We combined LRTM and host transcriptome data to construct a machine-learning model with 12 screened features to discriminate LRTIs and non-LRTIs. The results showed that the model trained by Random Forest in the validate set had the best performance (ROC AUC: 0.937, 95% CI: 0.832–1). The independent external dataset showed an accuracy of 76.5% for this model. This study suggests that the model integrating LRTM and host transcriptome data can be an effective tool for LRTIs diagnosis.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":"28 1","pages":""},"PeriodicalIF":9.2,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142214521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-11DOI: 10.1038/s41522-024-00550-4
Tianyuan Jia, Xianbiao Bi, Menglu Li, Chenhui Zhang, Anmin Ren, Shangru Li, Tian Zhou, Yingdan Zhang, Yang Liu, Xue Liu, Yinyue Deng, Bin Liu, Guobao Li, Liang Yang
Pseudomonas aeruginosa is a widespread nosocomial pathogen with a significant to cause both severe planktonic acute and biofilm-related chronic infections. Small RNAs (sRNAs) are noncoding regulatory molecules that are stabilized by the RNA chaperone Hfq to trigger various virulence-related signaling pathways. Here, we identified an Hfq-binding sRNA in P. aeruginosa PAO1, PqsS, which promotes bacterial pathogenicity and pseudomonas quinolone signal quorum sensing (pqs QS) system. Specifically, PqsS enhanced acute bacterial infections by inducing host cell death and promoting rhamnolipid-regulated swarming motility. Meanwhile, PqsS reduced chronic infection traits including biofilm formation and antibiotic resistance. Moreover, PqsS repressed pqsL transcript, increasing PQS levels for pqs QS. A PQS-rich environment promoted PqsS expression, thus forming a positive feedback loop. Furthermore, we demonstrated that the PqsS interacts and destabilizes the pqsL mRNA by recruiting RNase E to drive degradation. These findings provide insights for future research on P. aeruginosa pathogenesis and targeted treatment.
{"title":"Hfq-binding small RNA PqsS regulates Pseudomonas aeruginosa pqs quorum sensing system and virulence","authors":"Tianyuan Jia, Xianbiao Bi, Menglu Li, Chenhui Zhang, Anmin Ren, Shangru Li, Tian Zhou, Yingdan Zhang, Yang Liu, Xue Liu, Yinyue Deng, Bin Liu, Guobao Li, Liang Yang","doi":"10.1038/s41522-024-00550-4","DOIUrl":"https://doi.org/10.1038/s41522-024-00550-4","url":null,"abstract":"<p><i>Pseudomonas aeruginosa</i> is a widespread nosocomial pathogen with a significant to cause both severe planktonic acute and biofilm-related chronic infections. Small RNAs (sRNAs) are noncoding regulatory molecules that are stabilized by the RNA chaperone Hfq to trigger various virulence-related signaling pathways. Here, we identified an Hfq-binding sRNA in <i>P. aeruginosa</i> PAO1, PqsS, which promotes bacterial pathogenicity and <i>pseudomonas quinolone signal</i> quorum sensing (<i>pqs</i> QS) system. Specifically, PqsS enhanced acute bacterial infections by inducing host cell death and promoting rhamnolipid-regulated swarming motility. Meanwhile, PqsS reduced chronic infection traits including biofilm formation and antibiotic resistance. Moreover, PqsS repressed <i>pqsL</i> transcript, increasing PQS levels for <i>pqs</i> QS. A PQS-rich environment promoted PqsS expression, thus forming a positive feedback loop. Furthermore, we demonstrated that the PqsS interacts and destabilizes the <i>pqsL</i> mRNA by recruiting RNase E to drive degradation. These findings provide insights for future research on <i>P. aeruginosa</i> pathogenesis and targeted treatment.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":"53 1","pages":""},"PeriodicalIF":9.2,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142226935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}