The gut microbiota has been demonstrated to play a significant role in the pathogenesis of Parkinson's disease (PD). However, conflicting findings regarding specific microbial species have been reported, possibly due to confounding factors within human populations. Herein, our current study investigated the interaction between the gut microbiota and host in a non-human primate (NHP) PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) using a multi-omic approach and a self-controlled design. Our transcriptomic sequencing of peripheral blood leukocytes (PBL) identified key genes involved in pro-inflammatory cytokine dysregulation, mitochondrial function regulation, neuroprotection activation, and neurogenesis associated with PD, such as IL1B, ATP1A3, and SLC5A3. The metabolomic profiles in serum and feces consistently exhibited significant alterations, particularly those closely associated with inflammation, mitochondrial dysfunctions and neurodegeneration in PD, such as TUDCA, ethylmalonic acid, and L-homophenylalanine. Furthermore, fecal metagenome analysis revealed gut dysbiosis associated with PD, characterized by a significant decrease in alpha diversity and altered commensals, particularly species such as Streptococcus, Butyrivibrio, and Clostridium. Additionally, significant correlations were observed between PD-associated microbes and metabolites, such as sphingomyelin and phospholipids. Importantly, PDPC significantly reduced in both PD monkey feces and serum, exhibiting strong correlation with PD-associated genes and microbes, such as SLC5A3 and Butyrivibrio species. Moreover, such multi-omic differential biomarkers were linked to the clinical rating scales of PD monkeys. Our findings provided novel insights into understanding the potential role of key metabolites in the host-microbiota interaction involved in PD pathogenesis.
{"title":"Multiomics of parkinsonism cynomolgus monkeys highlights significance of metabolites in interaction between host and microbiota.","authors":"Jiang-Mei Gao, Shou-Yue Xia, Geoff Hide, Bi-Hai Li, Yi-Yan Liu, Zhi-Yuan Wei, Xiao-Ji Zhuang, Qing Yan, Yun Wang, Wei Yang, Jian-Huan Chen, Jun-Hua Rao","doi":"10.1038/s41522-024-00535-3","DOIUrl":"10.1038/s41522-024-00535-3","url":null,"abstract":"<p><p>The gut microbiota has been demonstrated to play a significant role in the pathogenesis of Parkinson's disease (PD). However, conflicting findings regarding specific microbial species have been reported, possibly due to confounding factors within human populations. Herein, our current study investigated the interaction between the gut microbiota and host in a non-human primate (NHP) PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) using a multi-omic approach and a self-controlled design. Our transcriptomic sequencing of peripheral blood leukocytes (PBL) identified key genes involved in pro-inflammatory cytokine dysregulation, mitochondrial function regulation, neuroprotection activation, and neurogenesis associated with PD, such as IL1B, ATP1A3, and SLC5A3. The metabolomic profiles in serum and feces consistently exhibited significant alterations, particularly those closely associated with inflammation, mitochondrial dysfunctions and neurodegeneration in PD, such as TUDCA, ethylmalonic acid, and L-homophenylalanine. Furthermore, fecal metagenome analysis revealed gut dysbiosis associated with PD, characterized by a significant decrease in alpha diversity and altered commensals, particularly species such as Streptococcus, Butyrivibrio, and Clostridium. Additionally, significant correlations were observed between PD-associated microbes and metabolites, such as sphingomyelin and phospholipids. Importantly, PDPC significantly reduced in both PD monkey feces and serum, exhibiting strong correlation with PD-associated genes and microbes, such as SLC5A3 and Butyrivibrio species. Moreover, such multi-omic differential biomarkers were linked to the clinical rating scales of PD monkeys. Our findings provided novel insights into understanding the potential role of key metabolites in the host-microbiota interaction involved in PD pathogenesis.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11282307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141766893","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 : 2024-07-24DOI: 10.1038/s41522-024-00532-6
Zhandong Cai, Taobing Yu, Weiyi Tan, Qianghua Zhou, Lingrui Liu, Hai Nian, Tengxiang Lian
Cadmium (Cd), a heavy metal, is negatively associated with plant growth. AMT (ammonium transporter) genes can confer Cd resistance and enhance nitrogen (N) uptake in soybeans. The potential of AMT genes to alleviate Cd toxicity by modulating rhizosphere microbiota remains unkonwn. Here, the rhizosphere microbial taxonomic and metabolic differences in three genotypes, i.e., double knockout and overexpression lines and wild type, were identified. The results showed that GmAMT2.1/2.2 genes could induce soybean to recruit beneficial microorganisms, such as Tumebacillus, Alicyclobacillus, and Penicillium, by altering metabolites. The bacterial, fungal, and cross-kingdom synthetic microbial communities (SynComs) formed by these microorganisms can help soybean resist Cd toxicity. The mechanisms by which SynComs help soybeans resist Cd stress include reducing Cd content, increasing ammonium (NH4+-N) uptake and regulating specific functional genes in soybeans. Overall, this study provides valuable insights for the developing microbial formulations that enhance Cd resistance in sustainable agriculture.
{"title":"GmAMT2.1/2.2-dependent ammonium nitrogen and metabolites shape rhizosphere microbiome assembly to mitigate cadmium toxicity.","authors":"Zhandong Cai, Taobing Yu, Weiyi Tan, Qianghua Zhou, Lingrui Liu, Hai Nian, Tengxiang Lian","doi":"10.1038/s41522-024-00532-6","DOIUrl":"10.1038/s41522-024-00532-6","url":null,"abstract":"<p><p>Cadmium (Cd), a heavy metal, is negatively associated with plant growth. AMT (ammonium transporter) genes can confer Cd resistance and enhance nitrogen (N) uptake in soybeans. The potential of AMT genes to alleviate Cd toxicity by modulating rhizosphere microbiota remains unkonwn. Here, the rhizosphere microbial taxonomic and metabolic differences in three genotypes, i.e., double knockout and overexpression lines and wild type, were identified. The results showed that GmAMT2.1/2.2 genes could induce soybean to recruit beneficial microorganisms, such as Tumebacillus, Alicyclobacillus, and Penicillium, by altering metabolites. The bacterial, fungal, and cross-kingdom synthetic microbial communities (SynComs) formed by these microorganisms can help soybean resist Cd toxicity. The mechanisms by which SynComs help soybeans resist Cd stress include reducing Cd content, increasing ammonium (NH<sub>4</sub><sup>+</sup>-N) uptake and regulating specific functional genes in soybeans. Overall, this study provides valuable insights for the developing microbial formulations that enhance Cd resistance in sustainable agriculture.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11266425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752284","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}
The dominant bacteria in the hindgut of calves play an important role in their growth and health, which could even lead to lifelong consequences. However, the identification of core probiotics in the hindgut and its mechanism regulating host growth remain unclear. Here, a total of 1045 fecal samples were analyzed by 16S rRNA gene sequencing from the 408 Holstein dairy calves at the age of 0, 14, 28, 42, 56, and 70 days to characterize the dynamic changes of core taxa. Moreover, the mechanisms of nutrient metabolism of calf growth regulated by core bacteria were investigated using multi-omics analyses. Finally, fecal microbiota transplantation (FMT) in mice were conducted to illustrate the potential beneficial effects of core bacteria. Four calf enterotypes were identified and enterotypes dominated by Bifidobacterium and Oscillospiraceae_UCG-005 were representative. The frequency of enterotype conversion shifted from variable to stable. The close relationship observed between phenotype and enterotype, revealing a potential pro-growth effect of Bifidobacterium, might be implemented by promoting the use of carbohydrate, activating the synthesis of volatile fatty acids, amino acids and vitamin B6, and inhibiting methane production in the hindgut. The FMT results indicated the beneficial effect of Bifidobacterium on host growth and hindgut development. These results support the notion that the Bifidobacterium-dominated fecal microbiome would be an important driving force for promoting the host growth in the early life. Our findings provide new insights into the potential probiotic mining and application strategies to promote the growth of young animals or improve their growth retardation.
{"title":"The Bifidobacterium-dominated fecal microbiome in dairy calves shapes the characteristic growth phenotype of host.","authors":"Yimin Zhuang, Shuai Liu, Duo Gao, Yiming Xu, Wen Jiang, Tianyu Chen, Jianxin Xiao, Jingjun Wang, Guobin Hou, Sumin Li, Xinjie Zhao, Yanting Huang, Shangru Li, Siyuan Zhang, Mengmeng Li, Wei Wang, Shengli Li, Zhijun Cao","doi":"10.1038/s41522-024-00534-4","DOIUrl":"10.1038/s41522-024-00534-4","url":null,"abstract":"<p><p>The dominant bacteria in the hindgut of calves play an important role in their growth and health, which could even lead to lifelong consequences. However, the identification of core probiotics in the hindgut and its mechanism regulating host growth remain unclear. Here, a total of 1045 fecal samples were analyzed by 16S rRNA gene sequencing from the 408 Holstein dairy calves at the age of 0, 14, 28, 42, 56, and 70 days to characterize the dynamic changes of core taxa. Moreover, the mechanisms of nutrient metabolism of calf growth regulated by core bacteria were investigated using multi-omics analyses. Finally, fecal microbiota transplantation (FMT) in mice were conducted to illustrate the potential beneficial effects of core bacteria. Four calf enterotypes were identified and enterotypes dominated by Bifidobacterium and Oscillospiraceae_UCG-005 were representative. The frequency of enterotype conversion shifted from variable to stable. The close relationship observed between phenotype and enterotype, revealing a potential pro-growth effect of Bifidobacterium, might be implemented by promoting the use of carbohydrate, activating the synthesis of volatile fatty acids, amino acids and vitamin B6, and inhibiting methane production in the hindgut. The FMT results indicated the beneficial effect of Bifidobacterium on host growth and hindgut development. These results support the notion that the Bifidobacterium-dominated fecal microbiome would be an important driving force for promoting the host growth in the early life. Our findings provide new insights into the potential probiotic mining and application strategies to promote the growth of young animals or improve their growth retardation.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11271470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734679","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 : 2024-07-18DOI: 10.1038/s41522-024-00528-2
Bob T Rosier, Alex Mira
In our opinion, the 'hang-time' of nitrate-containing products discussed in the letter by Green and Green is an interesting variable that should be considered when nitrate-based treatment or prevention strategies are designed. However, due to direct nitrate recycling after nitrate intake, products with a long 'hang-time' (e.g., chewing gum) may not always have an advantage compared to products with a short 'hang-time' (e.g., vegetable juices). We argue that extending the 'hang-time' is especially relevant and potentially beneficial for different applications, such as using a low nitrate dose to stimulate the oral effects, reaching oral tissues that may otherwise not be exposed to dietary nitrate (e.g., periodontal pockets), and providing a longer nitrate exposure in individuals with an impaired salivary flow. Apart from the 'hang-time', other important variables are the nitrate dose and source (e.g., different salts and vegetable extracts), as well as the desired effect (e.g., an oral effect versus systemic effects). Finally, we believe that the alterations in salivary microbiota observed before and after chewing three nitrate-rich gums over a period of ~5 h, as reported by Green and Green, could be considered beneficial. However, the oral microbiota composition is affected by the circadian rhythm and the effect of gum mastication should be evaluated. These results should thus be confirmed by a placebo-controlled study, where these confounding factors can be accounted for.
我们认为,格林和格林在信中讨论的含硝酸盐产品的 "悬挂时间 "是一个有趣的变量,在设计基于硝酸盐的治疗或预防策略时应加以考虑。然而,由于摄入硝酸盐后硝酸盐会被直接回收利用,与 "滞留时间 "较短的产品(如蔬菜汁)相比,"滞留时间 "较长的产品(如口香糖)并不总是具有优势。我们认为,延长 "悬挂时间 "对于不同的应用尤其重要,而且可能有益,例如使用低剂量硝酸盐来刺激口腔效应,使硝酸盐进入可能无法接触到膳食硝酸盐的口腔组织(如牙周袋),以及为唾液流量受损的人提供更长的硝酸盐接触时间。除了 "滞留时间 "外,其他重要变量还包括硝酸盐的剂量和来源(如不同的盐类和植物提取物),以及所期望的效果(如口腔效果和全身效果)。最后,我们认为 Green 和 Green 所报告的在咀嚼三种富含硝酸盐的口香糖前后约 5 小时内观察到的唾液微生物群的变化可以被认为是有益的。然而,口腔微生物群的组成受昼夜节律的影响,因此应评估咀嚼口香糖的影响。因此,这些结果应通过安慰剂对照研究加以证实,因为安慰剂对照研究可以考虑这些干扰因素。
{"title":"Topical prebiotic nitrate: optimizing the 'hang-time', source and dose for specific oral or systemic effects.","authors":"Bob T Rosier, Alex Mira","doi":"10.1038/s41522-024-00528-2","DOIUrl":"10.1038/s41522-024-00528-2","url":null,"abstract":"<p><p>In our opinion, the 'hang-time' of nitrate-containing products discussed in the letter by Green and Green is an interesting variable that should be considered when nitrate-based treatment or prevention strategies are designed. However, due to direct nitrate recycling after nitrate intake, products with a long 'hang-time' (e.g., chewing gum) may not always have an advantage compared to products with a short 'hang-time' (e.g., vegetable juices). We argue that extending the 'hang-time' is especially relevant and potentially beneficial for different applications, such as using a low nitrate dose to stimulate the oral effects, reaching oral tissues that may otherwise not be exposed to dietary nitrate (e.g., periodontal pockets), and providing a longer nitrate exposure in individuals with an impaired salivary flow. Apart from the 'hang-time', other important variables are the nitrate dose and source (e.g., different salts and vegetable extracts), as well as the desired effect (e.g., an oral effect versus systemic effects). Finally, we believe that the alterations in salivary microbiota observed before and after chewing three nitrate-rich gums over a period of ~5 h, as reported by Green and Green, could be considered beneficial. However, the oral microbiota composition is affected by the circadian rhythm and the effect of gum mastication should be evaluated. These results should thus be confirmed by a placebo-controlled study, where these confounding factors can be accounted for.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11258277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141724080","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 : 2024-07-18DOI: 10.1038/s41522-024-00527-3
Juliana Green, Shawn J Green
{"title":"Topical prebiotic nitrate: can extending the 'hang-time' in the mouth improve oral-vascular health outcomes?","authors":"Juliana Green, Shawn J Green","doi":"10.1038/s41522-024-00527-3","DOIUrl":"10.1038/s41522-024-00527-3","url":null,"abstract":"","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11258217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141724079","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 : 2024-07-13DOI: 10.1038/s41522-024-00529-1
Yu Wei, Gao-Peng Dang, Zhao-Yang Ren, Mei-Chen Wan, Chen-Yu Wang, Hong-Bo Li, Tong Zhang, Franklin R Tay, Li-Na Niu
Dental calculus severely affects the oral health of humans and animal pets. Calculus deposition affects the gingival appearance and causes inflammation. Failure to remove dental calculus from the dentition results in oral diseases such as periodontitis. Apart from adversely affecting oral health, some systemic diseases are closely related to dental calculus deposition. Hence, identifying the mechanisms of dental calculus formation helps protect oral and systemic health. A plethora of biological and physicochemical factors contribute to the physiological equilibrium in the oral cavity. Bacteria are an important part of the equation. Calculus formation commences when the bacterial equilibrium is broken. Bacteria accumulate locally and form biofilms on the tooth surface. The bacteria promote increases in local calcium and phosphorus concentrations, which triggers biomineralization and the development of dental calculus. Current treatments only help to relieve the symptoms caused by calculus deposition. These symptoms are prone to relapse if calculus removal is not under control. There is a need for a treatment regime that combines short-term and long-term goals in addressing calculus formation. The present review introduces the mechanisms of dental calculus formation, influencing factors, and the relationship between dental calculus and several systemic diseases. This is followed by the presentation of a conceptual solution for improving existing treatment strategies and minimizing recurrence.
{"title":"Recent advances in the pathogenesis and prevention strategies of dental calculus.","authors":"Yu Wei, Gao-Peng Dang, Zhao-Yang Ren, Mei-Chen Wan, Chen-Yu Wang, Hong-Bo Li, Tong Zhang, Franklin R Tay, Li-Na Niu","doi":"10.1038/s41522-024-00529-1","DOIUrl":"10.1038/s41522-024-00529-1","url":null,"abstract":"<p><p>Dental calculus severely affects the oral health of humans and animal pets. Calculus deposition affects the gingival appearance and causes inflammation. Failure to remove dental calculus from the dentition results in oral diseases such as periodontitis. Apart from adversely affecting oral health, some systemic diseases are closely related to dental calculus deposition. Hence, identifying the mechanisms of dental calculus formation helps protect oral and systemic health. A plethora of biological and physicochemical factors contribute to the physiological equilibrium in the oral cavity. Bacteria are an important part of the equation. Calculus formation commences when the bacterial equilibrium is broken. Bacteria accumulate locally and form biofilms on the tooth surface. The bacteria promote increases in local calcium and phosphorus concentrations, which triggers biomineralization and the development of dental calculus. Current treatments only help to relieve the symptoms caused by calculus deposition. These symptoms are prone to relapse if calculus removal is not under control. There is a need for a treatment regime that combines short-term and long-term goals in addressing calculus formation. The present review introduces the mechanisms of dental calculus formation, influencing factors, and the relationship between dental calculus and several systemic diseases. This is followed by the presentation of a conceptual solution for improving existing treatment strategies and minimizing recurrence.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11246453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603966","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 : 2024-07-03DOI: 10.1038/s41522-024-00525-5
Dongyu Wang, Pieter Candry, Kristopher A Hunt, Zachary Flinkstrom, Zheng Shi, Yunlong Liu, Neil Q Wofford, Michael J McInerney, Ralph S Tanner, Kara B De Leόn, Jizhong Zhou, Mari-Karoliina H Winkler, David A Stahl, Chongle Pan
Climate changes significantly impact greenhouse gas emissions from wetland soil. Specifically, wetland soil may be exposed to oxygen (O2) during droughts, or to sulfate (SO42-) as a result of sea level rise. How these stressors - separately and together - impact microbial food webs driving carbon cycling in the wetlands is still not understood. To investigate this, we integrated geochemical analysis, proteogenomics, and stoichiometric modeling to characterize the impact of elevated SO42- and O2 levels on microbial methane (CH4) and carbon dioxide (CO2) emissions. The results uncovered the adaptive responses of this community to changes in SO42- and O2 availability and identified altered microbial guilds and metabolic processes driving CH4 and CO2 emissions. Elevated SO42- reduced CH4 emissions, with hydrogenotrophic methanogenesis more suppressed than acetoclastic. Elevated O2 shifted the greenhouse gas emissions from CH4 to CO2. The metabolic effects of combined SO42- and O2 exposures on CH4 and CO2 emissions were similar to those of O2 exposure alone. The reduction in CH4 emission by increased SO42- and O2 was much greater than the concomitant increase in CO2 emission. Thus, greater SO42- and O2 exposure in wetlands is expected to reduce the aggregate warming effect of CH4 and CO2. Metaproteomics and stoichiometric modeling revealed a unique subnetwork involving carbon metabolism that converts lactate and SO42- to produce acetate, H2S, and CO2 when SO42- is elevated under oxic conditions. This study provides greater quantitative resolution of key metabolic processes necessary for the prediction of CH4 and CO2 emissions from wetlands under future climate scenarios.
{"title":"Metaproteomics-informed stoichiometric modeling reveals the responses of wetland microbial communities to oxygen and sulfate exposure.","authors":"Dongyu Wang, Pieter Candry, Kristopher A Hunt, Zachary Flinkstrom, Zheng Shi, Yunlong Liu, Neil Q Wofford, Michael J McInerney, Ralph S Tanner, Kara B De Leόn, Jizhong Zhou, Mari-Karoliina H Winkler, David A Stahl, Chongle Pan","doi":"10.1038/s41522-024-00525-5","DOIUrl":"10.1038/s41522-024-00525-5","url":null,"abstract":"<p><p>Climate changes significantly impact greenhouse gas emissions from wetland soil. Specifically, wetland soil may be exposed to oxygen (O<sub>2</sub>) during droughts, or to sulfate (SO<sub>4</sub><sup>2-</sup>) as a result of sea level rise. How these stressors - separately and together - impact microbial food webs driving carbon cycling in the wetlands is still not understood. To investigate this, we integrated geochemical analysis, proteogenomics, and stoichiometric modeling to characterize the impact of elevated SO<sub>4</sub><sup>2-</sup> and O<sub>2</sub> levels on microbial methane (CH<sub>4</sub>) and carbon dioxide (CO<sub>2</sub>) emissions. The results uncovered the adaptive responses of this community to changes in SO<sub>4</sub><sup>2-</sup> and O<sub>2</sub> availability and identified altered microbial guilds and metabolic processes driving CH<sub>4</sub> and CO<sub>2</sub> emissions. Elevated SO<sub>4</sub><sup>2-</sup> reduced CH<sub>4</sub> emissions, with hydrogenotrophic methanogenesis more suppressed than acetoclastic. Elevated O<sub>2</sub> shifted the greenhouse gas emissions from CH<sub>4</sub> to CO<sub>2</sub>. The metabolic effects of combined SO<sub>4</sub><sup>2-</sup> and O<sub>2</sub> exposures on CH<sub>4</sub> and CO<sub>2</sub> emissions were similar to those of O<sub>2</sub> exposure alone. The reduction in CH<sub>4</sub> emission by increased SO<sub>4</sub><sup>2-</sup> and O<sub>2</sub> was much greater than the concomitant increase in CO<sub>2</sub> emission. Thus, greater SO<sub>4</sub><sup>2-</sup> and O<sub>2</sub> exposure in wetlands is expected to reduce the aggregate warming effect of CH<sub>4</sub> and CO<sub>2</sub>. Metaproteomics and stoichiometric modeling revealed a unique subnetwork involving carbon metabolism that converts lactate and SO<sub>4</sub><sup>2-</sup> to produce acetate, H<sub>2</sub>S, and CO<sub>2</sub> when SO<sub>4</sub><sup>2-</sup> is elevated under oxic conditions. This study provides greater quantitative resolution of key metabolic processes necessary for the prediction of CH<sub>4</sub> and CO<sub>2</sub> emissions from wetlands under future climate scenarios.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11222425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498616","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 : 2024-06-28DOI: 10.1038/s41522-024-00526-4
Alessandro Tanca, Antonio Palomba, Giovanni Fiorito, Marcello Abbondio, Daniela Pagnozzi, Sergio Uzzau
Gut metaproteomics can provide direct evidence of microbial functions actively expressed in the colonic environments, contributing to clarify the role of the gut microbiota in human physiology. In this study, we re-analyzed 10 fecal metaproteomics datasets of healthy individuals from different continents and countries, with the aim of identifying stable and variable gut microbial functions and defining the contribution of specific bacterial taxa to the main metabolic pathways. The "core" metaproteome included 182 microbial functions and 83 pathways that were identified in all individuals analyzed. Several enzymes involved in glucose and pyruvate metabolism, along with glutamate dehydrogenase, acetate kinase, elongation factors G and Tu and DnaK, were the proteins with the lowest abundance variability in the cohorts under study. On the contrary, proteins involved in chemotaxis, response to stress and cell adhesion were among the most variable functions. Random-effect meta-analysis of correlation trends between taxa, functions and pathways revealed key ecological and molecular associations within the gut microbiota. The contribution of specific bacterial taxa to the main biological processes was also investigated, finding that Faecalibacterium is the most stable genus and the top contributor to anti-inflammatory butyrate production in the healthy gut microbiota. Active production of other mucosal immunomodulators facilitating host tolerance was observed, including Roseburia flagellin and lipopolysaccharide biosynthetic enzymes expressed by members of Bacteroidota. Our study provides a detailed picture of the healthy human gut microbiota, contributing to unveil its functional mechanisms and its relationship with nutrition, immunity, and environmental stressors.
肠道元蛋白质组学可以提供结肠环境中积极表达的微生物功能的直接证据,有助于阐明肠道微生物群在人类生理学中的作用。在这项研究中,我们重新分析了来自不同大洲和国家的 10 个健康人的粪便元蛋白质组数据集,目的是确定稳定和可变的肠道微生物功能,并定义特定细菌类群对主要代谢途径的贡献。核心 "元蛋白质组包括 182 种微生物功能和 83 条通路,这些功能和通路在所有分析对象中都得到了确定。参与葡萄糖和丙酮酸代谢的几种酶,以及谷氨酸脱氢酶、乙酸激酶、伸长因子 G 和 Tu 以及 DnaK,是所研究群体中丰度变化最小的蛋白质。相反,参与趋化、应激反应和细胞粘附的蛋白质的功能变化最大。对分类群、功能和途径之间相关趋势的随机效应荟萃分析揭示了肠道微生物群中的关键生态和分子关联。研究还调查了特定细菌类群对主要生物过程的贡献,发现粪杆菌是最稳定的菌属,也是健康肠道微生物群中产生抗炎丁酸盐的最大贡献者。研究还观察到了其他促进宿主耐受性的粘膜免疫调节剂的活性生产,包括由类菌群成员表达的蔷薇鞭毛菌素和脂多糖生物合成酶。我们的研究提供了健康人体肠道微生物群的详细情况,有助于揭示其功能机制及其与营养、免疫和环境压力因素的关系。
{"title":"Metaproteomic portrait of the healthy human gut microbiota.","authors":"Alessandro Tanca, Antonio Palomba, Giovanni Fiorito, Marcello Abbondio, Daniela Pagnozzi, Sergio Uzzau","doi":"10.1038/s41522-024-00526-4","DOIUrl":"10.1038/s41522-024-00526-4","url":null,"abstract":"<p><p>Gut metaproteomics can provide direct evidence of microbial functions actively expressed in the colonic environments, contributing to clarify the role of the gut microbiota in human physiology. In this study, we re-analyzed 10 fecal metaproteomics datasets of healthy individuals from different continents and countries, with the aim of identifying stable and variable gut microbial functions and defining the contribution of specific bacterial taxa to the main metabolic pathways. The \"core\" metaproteome included 182 microbial functions and 83 pathways that were identified in all individuals analyzed. Several enzymes involved in glucose and pyruvate metabolism, along with glutamate dehydrogenase, acetate kinase, elongation factors G and Tu and DnaK, were the proteins with the lowest abundance variability in the cohorts under study. On the contrary, proteins involved in chemotaxis, response to stress and cell adhesion were among the most variable functions. Random-effect meta-analysis of correlation trends between taxa, functions and pathways revealed key ecological and molecular associations within the gut microbiota. The contribution of specific bacterial taxa to the main biological processes was also investigated, finding that Faecalibacterium is the most stable genus and the top contributor to anti-inflammatory butyrate production in the healthy gut microbiota. Active production of other mucosal immunomodulators facilitating host tolerance was observed, including Roseburia flagellin and lipopolysaccharide biosynthetic enzymes expressed by members of Bacteroidota. Our study provides a detailed picture of the healthy human gut microbiota, contributing to unveil its functional mechanisms and its relationship with nutrition, immunity, and environmental stressors.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11214629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469769","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 : 2024-06-25DOI: 10.1038/s41522-024-00518-4
Evgenia Maslova, Lara EisaianKhongi, Petra Rigole, Tom Coenye, Ronan R McCarthy
It is becoming increasingly apparent that commensal skin bacteria have an important role in wound healing and infection progression. However, the precise mechanisms underpinning many of these probiotic interactions remain to be fully uncovered. In this work, we demonstrate that the common skin commensal Cutibacterium acnes can limit the pathogenicity of the prevalent wound pathogen Pseudomonas aeruginosa in vivo. We show that this impact on pathogenicity is independent of any effect on growth, but occurs through a significant downregulation of the Type Three Secretion System (T3SS), the primary toxin secretion system utilised by P. aeruginosa in eukaryotic infection. We also show a downregulation in glucose acquisition systems, a known regulator of the T3SS, suggesting that glucose availability in a wound can influence infection progression. C. acnes is well known as a glucose fermenting organism, and we demonstrate that topically supplementing a wound with glucose reverses the probiotic effects of C. acnes. This suggests that introducing carbon source competition within the wound microenvironment may be an effective way to prevent or limit wound infection.
{"title":"Carbon source competition within the wound microenvironment can significantly influence infection progression.","authors":"Evgenia Maslova, Lara EisaianKhongi, Petra Rigole, Tom Coenye, Ronan R McCarthy","doi":"10.1038/s41522-024-00518-4","DOIUrl":"10.1038/s41522-024-00518-4","url":null,"abstract":"<p><p>It is becoming increasingly apparent that commensal skin bacteria have an important role in wound healing and infection progression. However, the precise mechanisms underpinning many of these probiotic interactions remain to be fully uncovered. In this work, we demonstrate that the common skin commensal Cutibacterium acnes can limit the pathogenicity of the prevalent wound pathogen Pseudomonas aeruginosa in vivo. We show that this impact on pathogenicity is independent of any effect on growth, but occurs through a significant downregulation of the Type Three Secretion System (T3SS), the primary toxin secretion system utilised by P. aeruginosa in eukaryotic infection. We also show a downregulation in glucose acquisition systems, a known regulator of the T3SS, suggesting that glucose availability in a wound can influence infection progression. C. acnes is well known as a glucose fermenting organism, and we demonstrate that topically supplementing a wound with glucose reverses the probiotic effects of C. acnes. This suggests that introducing carbon source competition within the wound microenvironment may be an effective way to prevent or limit wound infection.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11199515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141451078","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}
The progression of colorectal cancer is closely associated with diet. Fasting-mimicking diet (FMD) is a promising type of dietary intervention that have beneficial effects in the prevention and treatment of various cancers. We investigated the therapeutic effect of 4-day FMD against colorectal cancer in mice through immune cell analysis, microbiota composition analysis and anti-PD-1 treatment. These FMD cycles effectively suppressed colorectal cancer growth, reduced cell proliferation and angiogenesis, increased tumor-infiltration lymphocytes especially CD8+T cells. FMD stimulated protective gut microbiota, especially Lactobacillus. Supplementation of Lactobacillus johnsonii induced similar results as FMD intervention, which also suppressed tumor growth and increased CD45+ and CD8+ T cells. Additionally, FMD synthesizing with anti-PD-1 therapy effectively inhibited CRC progression. These findings suggest that Lactobacillus. johnsonii is necessary for the anticancer process of FMD in CRC. FMD through its effects on both gut microbiota and immune system, effectively suppressed colorectal cancer progression in mouse model.
{"title":"Fasting-mimicking diet remodels gut microbiota and suppresses colorectal cancer progression.","authors":"Man Luo, Qingyi Wang, Yong Sun, Yao Jiang, Qiwen Wang, Yanrou Gu, Zhefang Hu, Qianyi Chen, Jilei Xu, Shujie Chen, Tongyao Hou, Lijun Feng","doi":"10.1038/s41522-024-00520-w","DOIUrl":"10.1038/s41522-024-00520-w","url":null,"abstract":"<p><p>The progression of colorectal cancer is closely associated with diet. Fasting-mimicking diet (FMD) is a promising type of dietary intervention that have beneficial effects in the prevention and treatment of various cancers. We investigated the therapeutic effect of 4-day FMD against colorectal cancer in mice through immune cell analysis, microbiota composition analysis and anti-PD-1 treatment. These FMD cycles effectively suppressed colorectal cancer growth, reduced cell proliferation and angiogenesis, increased tumor-infiltration lymphocytes especially CD8<sup>+</sup>T cells. FMD stimulated protective gut microbiota, especially Lactobacillus. Supplementation of Lactobacillus johnsonii induced similar results as FMD intervention, which also suppressed tumor growth and increased CD45<sup>+</sup> and CD8<sup>+</sup> T cells. Additionally, FMD synthesizing with anti-PD-1 therapy effectively inhibited CRC progression. These findings suggest that Lactobacillus. johnsonii is necessary for the anticancer process of FMD in CRC. FMD through its effects on both gut microbiota and immune system, effectively suppressed colorectal cancer progression in mouse model.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11199600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141451079","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}