Childhood malnutrition is a metabolic condition that affects the physical and mental well-being of children and leads to resultant disorders in maturity. The development of childhood malnutrition is influenced by a number of physiological and environmental factors including metabolic stress, infections, diet, genetic variables, and gut microbiota. The imbalanced gut microbiota is one of the main environmental risk factors that significantly influence host physiology and childhood malnutrition progression. In this review, we have evaluated the gut microbiota association with undernutrition and overnutrition in children, and then the quantitative and qualitative significance of gut dysbiosis in order to reveal the impact of gut microbiota modification using probiotics, prebiotics, synbiotics, postbiotics, fecal microbiota transplantation, and engineering biology methods as new therapeutic challenges in the management of disturbed energy homeostasis. Understanding the host–microbiota interaction and the remote regulation of other organs and pathways by gut microbiota can improve the effectiveness of new therapeutic approaches and mitigate the negative consequences of childhood malnutrition.
{"title":"Gut microbiota and childhood malnutrition: Understanding the link and exploring therapeutic interventions","authors":"Sevda Zoghi, Fatemah Sadeghpour Heravi, Zeinab Nikniaz, Masoud Shirmohamadi, Seyed Yaghoub Moaddab, Hamed Ebrahimzadeh Leylabadlo","doi":"10.1002/elsc.202300070","DOIUrl":"10.1002/elsc.202300070","url":null,"abstract":"<p>Childhood malnutrition is a metabolic condition that affects the physical and mental well-being of children and leads to resultant disorders in maturity. The development of childhood malnutrition is influenced by a number of physiological and environmental factors including metabolic stress, infections, diet, genetic variables, and gut microbiota. The imbalanced gut microbiota is one of the main environmental risk factors that significantly influence host physiology and childhood malnutrition progression. In this review, we have evaluated the gut microbiota association with undernutrition and overnutrition in children, and then the quantitative and qualitative significance of gut dysbiosis in order to reveal the impact of gut microbiota modification using probiotics, prebiotics, synbiotics, postbiotics, fecal microbiota transplantation, and engineering biology methods as new therapeutic challenges in the management of disturbed energy homeostasis. Understanding the host–microbiota interaction and the remote regulation of other organs and pathways by gut microbiota can improve the effectiveness of new therapeutic approaches and mitigate the negative consequences of childhood malnutrition.</p>","PeriodicalId":11678,"journal":{"name":"Engineering in Life Sciences","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/elsc.202300070","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135482137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cover Picture: Engineering in Life Sciences 10'23","authors":"","doi":"10.1002/elsc.202370101","DOIUrl":"https://doi.org/10.1002/elsc.202370101","url":null,"abstract":"","PeriodicalId":11678,"journal":{"name":"Engineering in Life Sciences","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/elsc.202370101","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50119888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Riekje Biermann, Laura Rösner, Lisa-Marie Beyer, Laura Niemeyer, Sascha Beutel
Bacillus coagulans is a promising probiotic, because it combines probiotic properties of Lactobacillus and the ability of Bacillus to form endospores. Due to this hybrid relationship, cultivation of this organism is challenging. As the probiotics market continues to grow, there is a new focus on the production of these microorganisms. In this work, a strain‐specific bioprocess for B. coagulans was developed to support growth on one hand and ensure sporulation on the other hand. This circumstance is not trivial, since these two metabolic states are contrary. The developed bioprocess uses a modified chemically defined medium which was further investigated in a one‐factor‐at‐a‐time assay after adaptation. A transfer from the shake flask to the bioreactor was successfully demonstrated in the scope of this work. The investigated process parameters included temperature, agitation and pH‐control. Especially the pH‐control improved the sporulation in the bioreactor when compared to shake flasks. The bioprocess resulted in a sporulation efficiency of 80%–90%. This corresponds to a sevenfold increase in sporulation efficiency due to a transfer to the bioreactor with pH‐control. Additionally, a design of experiment (DoE) was conducted to test the robustness of the bioprocess. This experiment validated the beforementioned sporulation efficiency for the developed bioprocess. Afterwards the bioprocess was then scaled up from a 1 L scale to a 10 L bioreactor scale. A comparable sporulation efficiency of 80% as in the small scale was achieved. The developed bioprocess facilitates the upscaling and application to an industrial scale, and can thus help meet the increasing market for probiotics.
{"title":"Bioprocess development for endospore production by Bacillus coagulans using an optimized chemically defined medium","authors":"Riekje Biermann, Laura Rösner, Lisa-Marie Beyer, Laura Niemeyer, Sascha Beutel","doi":"10.1002/elsc.202300210","DOIUrl":"https://doi.org/10.1002/elsc.202300210","url":null,"abstract":"Bacillus coagulans is a promising probiotic, because it combines probiotic properties of Lactobacillus and the ability of Bacillus to form endospores. Due to this hybrid relationship, cultivation of this organism is challenging. As the probiotics market continues to grow, there is a new focus on the production of these microorganisms. In this work, a strain‐specific bioprocess for B. coagulans was developed to support growth on one hand and ensure sporulation on the other hand. This circumstance is not trivial, since these two metabolic states are contrary. The developed bioprocess uses a modified chemically defined medium which was further investigated in a one‐factor‐at‐a‐time assay after adaptation. A transfer from the shake flask to the bioreactor was successfully demonstrated in the scope of this work. The investigated process parameters included temperature, agitation and pH‐control. Especially the pH‐control improved the sporulation in the bioreactor when compared to shake flasks. The bioprocess resulted in a sporulation efficiency of 80%–90%. This corresponds to a sevenfold increase in sporulation efficiency due to a transfer to the bioreactor with pH‐control. Additionally, a design of experiment (DoE) was conducted to test the robustness of the bioprocess. This experiment validated the beforementioned sporulation efficiency for the developed bioprocess. Afterwards the bioprocess was then scaled up from a 1 L scale to a 10 L bioreactor scale. A comparable sporulation efficiency of 80% as in the small scale was achieved. The developed bioprocess facilitates the upscaling and application to an industrial scale, and can thus help meet the increasing market for probiotics.","PeriodicalId":11678,"journal":{"name":"Engineering in Life Sciences","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/elsc.202300210","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50134360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gabriele Recanati, Magdalena Pappenreiter, Christoph Gstoettner, Patrick Scheidl, Elena Domínguez Vega, Bernhard Sissolak, Alois Jungbauer
Continuous precipitation coupled with continuous tangential flow filtration is a cost-effective alternative for the capture of recombinant antibodies from crude cell culture supernatant. The removal of surge tanks between unit operations, by the adoption of tubular reactors, maintains a continuous harvest and mass flow of product with the advantage of a narrow residence time distribution (RTD). We developed a continuous process implementing two orthogonal precipitation methods, CaCl2 precipitation for removal of host-cell DNA and polyethylene glycol (PEG) for capturing the recombinant antibody, with no influence on the glycosylation profile. Our lab-scale prototype consisting of two tubular reactors and two stages of tangential flow microfiltration was continuously operated for up to 8 days in a truly continuous fashion and without any product flow interruption, both as a stand-alone capture and as an integrated perfusion-capture. Furthermore, we explored the use of a negatively charged membrane adsorber for flow-through anion exchange as first polishing step. We obtained a product recovery of approximately 80% and constant product quality, with more than two logarithmic reduction values (LRVs) for both host-cell proteins and host-cell DNA by the combination of the precipitation-based capture and the first polishing step.
{"title":"Integration of a perfusion reactor and continuous precipitation in an entirely membrane-based process for antibody capture","authors":"Gabriele Recanati, Magdalena Pappenreiter, Christoph Gstoettner, Patrick Scheidl, Elena Domínguez Vega, Bernhard Sissolak, Alois Jungbauer","doi":"10.1002/elsc.202300219","DOIUrl":"10.1002/elsc.202300219","url":null,"abstract":"<p>Continuous precipitation coupled with continuous tangential flow filtration is a cost-effective alternative for the capture of recombinant antibodies from crude cell culture supernatant. The removal of surge tanks between unit operations, by the adoption of tubular reactors, maintains a continuous harvest and mass flow of product with the advantage of a narrow residence time distribution (RTD). We developed a continuous process implementing two orthogonal precipitation methods, CaCl<sub>2</sub> precipitation for removal of host-cell DNA and polyethylene glycol (PEG) for capturing the recombinant antibody, with no influence on the glycosylation profile. Our lab-scale prototype consisting of two tubular reactors and two stages of tangential flow microfiltration was continuously operated for up to 8 days in a truly continuous fashion and without any product flow interruption, both as a stand-alone capture and as an integrated perfusion-capture. Furthermore, we explored the use of a negatively charged membrane adsorber for flow-through anion exchange as first polishing step. We obtained a product recovery of approximately 80% and constant product quality, with more than two logarithmic reduction values (LRVs) for both host-cell proteins and host-cell DNA by the combination of the precipitation-based capture and the first polishing step.</p>","PeriodicalId":11678,"journal":{"name":"Engineering in Life Sciences","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/elsc.202300219","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41114057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cover Picture: Engineering in Life Sciences 9'23","authors":"","doi":"10.1002/elsc.202370091","DOIUrl":"https://doi.org/10.1002/elsc.202370091","url":null,"abstract":"","PeriodicalId":11678,"journal":{"name":"Engineering in Life Sciences","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/elsc.202370091","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50117492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Johanna S. Rehfeld, Louis M. Kuhnke, Christian Ude, Gernot T. John, Sascha Beutel
In the field of bioprocess development miniaturization, parallelization and flexibility play a key role reducing costs and time. To precisely meet these requirements, additive manufacturing (3D-printing) is an ideal technology. 3D-printing enables rapid prototyping and cost-effective fabrication of individually designed devices with complex geometries on demand. For successful bioprocess development, monitoring of process-relevant parameters, such as pH, dissolved oxygen (DO), and biomass, is crucial. Online monitoring is preferred as offline sampling is time-consuming and leads to loss of information. In this study, 3D-printed cultivation vessels with optical prisms are evaluated for the use in upstream processes of different industrially relevant microorganisms and cell lines. It was shown, that the 3D-printed optically modified well (OMW) is of benefit for a wide range of biotechnologically relevant microorganisms and even for mammalian suspension cells. Evaluation tests with Escherichia coli, Bacillus subtilis, Saccharomyces cerevisiae, and Chinese hamster ovary (CHO) cells were performed, providing highly reproducible results. Growth behavior of OMW cultures was comparable to behavior of shake flask (SF) cultivations and the signal to noise ratio in online biomass measurement was shown to be reduced up to 95.8% by using the OMW. Especially the cultivation phases with low turbidity respective optical densities below 1.0 rel.AU could be monitored accurately for the first time. Furthermore, it was demonstrated that the 3D-printed optics are transferable to different well geometries and sizes, enabling efficient biomass monitoring for individual requirements with tailor-made 3D-printed cultivation vessels in small scale.
{"title":"Investigation and evaluation of a 3D-printed optical modified cultivation vessel for improved scattered light measurement of biotechnologically relevant organisms","authors":"Johanna S. Rehfeld, Louis M. Kuhnke, Christian Ude, Gernot T. John, Sascha Beutel","doi":"10.1002/elsc.202300204","DOIUrl":"10.1002/elsc.202300204","url":null,"abstract":"<p>In the field of bioprocess development miniaturization, parallelization and flexibility play a key role reducing costs and time. To precisely meet these requirements, additive manufacturing (3D-printing) is an ideal technology. 3D-printing enables rapid prototyping and cost-effective fabrication of individually designed devices with complex geometries on demand. For successful bioprocess development, monitoring of process-relevant parameters, such as pH, dissolved oxygen (DO), and biomass, is crucial. Online monitoring is preferred as offline sampling is time-consuming and leads to loss of information. In this study, 3D-printed cultivation vessels with optical prisms are evaluated for the use in upstream processes of different industrially relevant microorganisms and cell lines. It was shown, that the 3D-printed optically modified well (OMW) is of benefit for a wide range of biotechnologically relevant microorganisms and even for mammalian suspension cells. Evaluation tests with <i>Escherichia coli</i>, <i>Bacillus subtilis</i>, <i>Saccharomyces cerevisiae</i>, and Chinese hamster ovary (CHO) cells were performed, providing highly reproducible results. Growth behavior of OMW cultures was comparable to behavior of shake flask (SF) cultivations and the signal to noise ratio in online biomass measurement was shown to be reduced up to 95.8% by using the OMW. Especially the cultivation phases with low turbidity respective optical densities below 1.0 rel.AU could be monitored accurately for the first time. Furthermore, it was demonstrated that the 3D-printed optics are transferable to different well geometries and sizes, enabling efficient biomass monitoring for individual requirements with tailor-made 3D-printed cultivation vessels in small scale.</p>","PeriodicalId":11678,"journal":{"name":"Engineering in Life Sciences","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b5/2b/ELSC-23-e2300204.PMC10472911.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10152389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human activities have led to the release of various environmental pollutants, triggering ecological challenges. In situ, microbial communities in these contaminated environments are usually assumed to possess the potential capacity of pollutant degradation. However, the majority of genes and microorganisms in these environments remain uncharacterized and uncultured. The advent of meta-omics provided culture-independent solutions for exploring the functional genes and microorganisms within complex microbial communities. In this review, we highlight the applications and methodologies of meta-omics in uncovering of genes and microbes from contaminated environments. These findings may assist in future bioremediation research.
{"title":"Meta-omics assisted microbial gene and strain resources mining in contaminant environment","authors":"Yiqun Huang, Haiyang Hu, Tingting Zhang, Weiwei Wang, Wenzhao Liu, Hongzhi Tang","doi":"10.1002/elsc.202300207","DOIUrl":"10.1002/elsc.202300207","url":null,"abstract":"<p>Human activities have led to the release of various environmental pollutants, triggering ecological challenges. In situ, microbial communities in these contaminated environments are usually assumed to possess the potential capacity of pollutant degradation. However, the majority of genes and microorganisms in these environments remain uncharacterized and uncultured. The advent of meta-omics provided culture-independent solutions for exploring the functional genes and microorganisms within complex microbial communities. In this review, we highlight the applications and methodologies of meta-omics in uncovering of genes and microbes from contaminated environments. These findings may assist in future bioremediation research.</p>","PeriodicalId":11678,"journal":{"name":"Engineering in Life Sciences","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/elsc.202300207","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47189884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cover Picture: Engineering in Life Sciences 8'23","authors":"","doi":"10.1002/elsc.202370081","DOIUrl":"https://doi.org/10.1002/elsc.202370081","url":null,"abstract":"","PeriodicalId":11678,"journal":{"name":"Engineering in Life Sciences","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/elsc.202370081","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50149299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Keven Lothert, Yasmina M. J. Harsy, Patrick Endres, Egbert Müller, Michael W. Wolff
Recently, multimodal chromatography using restricted access media (RAM) for the purification of nanoparticles, such as viruses has regained increasing attention. These chromatography resins combine size exclusion on the particle shell and adsorptive interaction within the core. Accordingly, smaller process-related impurities, for example, DNA and proteins, can be retained, while larger product viruses can pass unhindered. We evaluated a range of currently available RAM, differing in the shells’ pore cut-off and the core chemistry, for the purification of a cell culture-derived clarified model virus, namely the Orf virus (ORFV). We examined impurity depletion and product recovery as relevant criteria for the evaluation of column performance, as well as scale-up robustness and regeneration potential for evaluating a multiple use application. The results indicate that some columns, for example, the Capto Core, enable both a high DNA and protein removal, while others, for example, the Monomix Core 60 (MC60), are more suitable for DNA depletion. Furthermore, column regeneration is facilitated by using columns with larger shell pores (5000 vs. 700 kDa) and weaker binding interactions (anion exchange vs. multimodal). According to these findings, the choice of RAM resins should be selected according to the respective feed sample composition and the planned number of application cycles.
近年来,利用受限存取介质(RAM)进行纳米颗粒(如病毒)纯化的多模态色谱技术越来越受到人们的关注。这些色谱树脂结合了颗粒壳上的尺寸排除和核心内的吸附相互作用。因此,可以保留较小的工艺相关杂质,例如DNA和蛋白质,而较大的产品病毒可以不受阻碍地通过。我们评估了一系列目前可用的RAM,不同于外壳的孔切断和核心化学成分,用于纯化细胞培养衍生的澄清模型病毒,即Orf病毒(ORFV)。我们检查了杂质消耗和产品回收作为评估色谱柱性能的相关标准,以及评估多种用途应用的放大稳健性和再生潜力。结果表明,一些色谱柱(如Capto Core)可以同时去除DNA和蛋白质,而另一些色谱柱(如Monomix Core 60 (MC60))更适合去除DNA。此外,使用具有较大壳孔(5000 kDa vs 700 kDa)和较弱结合相互作用(阴离子交换vs多模态)的柱有助于柱再生。根据这些发现,RAM树脂的选择应根据各自的饲料样品组成和计划的应用周期数量来选择。
{"title":"Evaluation of restricted access media for the purification of cell culture-derived Orf viruses","authors":"Keven Lothert, Yasmina M. J. Harsy, Patrick Endres, Egbert Müller, Michael W. Wolff","doi":"10.1002/elsc.202300009","DOIUrl":"10.1002/elsc.202300009","url":null,"abstract":"<p>Recently, multimodal chromatography using restricted access media (RAM) for the purification of nanoparticles, such as viruses has regained increasing attention. These chromatography resins combine size exclusion on the particle shell and adsorptive interaction within the core. Accordingly, smaller process-related impurities, for example, DNA and proteins, can be retained, while larger product viruses can pass unhindered. We evaluated a range of currently available RAM, differing in the shells’ pore cut-off and the core chemistry, for the purification of a cell culture-derived clarified model virus, namely the Orf virus (ORFV). We examined impurity depletion and product recovery as relevant criteria for the evaluation of column performance, as well as scale-up robustness and regeneration potential for evaluating a multiple use application. The results indicate that some columns, for example, the Capto Core, enable both a high DNA and protein removal, while others, for example, the Monomix Core 60 (MC60), are more suitable for DNA depletion. Furthermore, column regeneration is facilitated by using columns with larger shell pores (5000 vs. 700 kDa) and weaker binding interactions (anion exchange vs. multimodal). According to these findings, the choice of RAM resins should be selected according to the respective feed sample composition and the planned number of application cycles.</p>","PeriodicalId":11678,"journal":{"name":"Engineering in Life Sciences","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2023-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/elsc.202300009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10150416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}