scholarly journals Decoding molecular markers and transcriptional circuitry of naive and primed states of human pluripotency

2020 ◽  
Author(s):  
Arindam Ghosh ◽  
Anup Som
Keyword(s):  
Transcription Factors ◽  
Molecular Mechanisms ◽  
System Development ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
List Type ◽  
Metabolic Processes ◽  
Primed State

ABSTRACTPluripotent stem cells (PSCs) have been observed to occur in two distinct states — naive and primed. Both naive and primed state PSCs can give rise to tissues of all the three germ layers in vitro but differ in their potential to generate germline chimera in vivo. Understanding the molecular mechanisms that govern these two states of pluripotency in human can open up a plethora of opportunities for studying early embryonic development and in biomedical applications. In this work, we use weighted gene co-expression network (WGCN) approach to identify the key molecular makers and their interactions that define the two distinct pluripotency states. Signed-hybrid WGCN was reconstructed from transcriptomic data (RNA-seq) of naive and primed state pluripotent samples. Our analysis revealed two sets of genes that are involved in establishment and maintenance of naive (4791 genes) and primed (5066 genes) states. The naive state genes were found to be enriched for biological processes and pathways related to metabolic processes while primed state genes were associated with system development. Further, we identified the top 10% genes by intra-modular connectivity as hubs and the hub transcription factors for each group, thus providing a three-tier list of genes associated with naive and primed states of pluripotency in human.HIGHLIGHTSWeighted gene co-expression network analysis (WGCNA) identified 4791 and 5066 genes to be involved in naive and primed states of human pluripotency respectively.Functional and pathway enrichment analysis revealed the naive genes were mostly related to metabolic processes and primed genes to system development.The top 10% genes based on intra-modular connectivity from each group were defined as hubs.Identified 52 and 33 transcription factors among the naive and primed module hubs respectively.The transcription factors might play a switch on-off mechanism in induction of the two pluripotent states.

scholarly journals Oct4 regulates embryonic pluripotency via metabolic mechanisms and Stat3 signalling

2020 ◽  
Author(s):  
Giuliano Giuseppe Stirparo ◽  
Agata Kurowski ◽  
Stanley Eugene Strawbridge ◽  
Hannah Stuart ◽  
Thorsten Edwin Boroviak ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Single Cell ◽  
Inner Cell Mass ◽  
Cell Mass ◽  
Ectopic Expression ◽  
Specific Gene ◽  
List Type ◽  
Early Mouse

AbstractOCT4 is a fundamental component of the molecular circuitry governing pluripotency in vivo and in vitro. To determine how OCT4 protects the pluripotent lineage from differentiation into trophoblast, we used single cell transcriptomics and quantitative immunofluorescence on blastocysts and established differentially expressed genes and pathways between control and OCT4 null cells. Activation of most pluripotency-associated transcription factors in the early mouse inner cell mass appears independent of OCT4, whereas JAK/STAT signalling requires OCT4, via activation of IL6ST. Single cell deconvolution, diffusion component and trajectory inference dissected the process of differentiation of OCT4 null cells by activating specific gene-network and transcription factors. Downregulation of glycolytic and oxidative metabolism was observed. CHIPseq analysis suggests OCT4 directly targets rate-limiting glycolytic enzymes. Concomitant with significant disruption of the STAT3 pathway, oxidative respiration is significantly diminished in OCT4 null cells. Upregulation of the lysosomal pathway detected in OCT4 null embryos is likely attributable to aberrant metabolism.Highlights and noveltyMajor pluripotency-associated transcription factors are activated in OCT4-deficient early mouse ICM cells, coincident with ectopic expression of trophectoderm markersJAK/STAT signalling is defective in OCT4 null embryosOCT4 promotes expression of KATS enzymes by means of glycolytic production of Acetyl CoA to secure chromatin accessibility for acquisition of epiblast identityOCT4 regulates the metabolic and biophysical processes required for establishment of embryonic pluripotency

scholarly journals Exosomal miR-199a-5p Inhibits Tumorigenesis and Angiogenesis by Targeting VEGFA in Osteosarcoma

2021 ◽  
Author(s):  
Lu Zhang ◽  
Hongxin Cao ◽  
Guanghui Gu ◽  
Dehui Hou ◽  
Yunhao You ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Luciferase Reporter ◽  
Pathway Enrichment Analysis ◽  
Osteosarcoma Cell ◽  
Plasma Samples ◽  
Osteosarcoma Cells ◽  
Hub Genes

Abstract Background: Osteosarcoma (OS) is the most common primary bone malignancy in children and adolescents. microRNAs have been found to play a vital role in tumor angiogenesis. Here, we investigated the effects of miR-199a-5p on tumor growth and angiogenesis in osteosarcoma. Furthermore, the underlying molecular mechanisms and signaling pathways were explored.Methods: The datasets were extracted from the Gene Expression Omnibus and the differentially expressed miRNAs (DEmiRNAs) were screened out by the GEO2R online platform. The potential target genes were predicted using the miRTarBase database. The predicted target genes were further analyzed by Gene Ontology and pathway enrichment analysis and a regulatory network of DEmiRNAs and their target genes was constructed. In addition, the effects of osteosarcoma cell derived exosomal miR-199a-5p on the proliferation, migration and neovascularization of HUVECs were evaluated by conducting EdU assays, Transwell experiments and tube formation assays. A dual-luciferase reporter assay was performed to detect whether VEGFA was the direct target of miR-199a-5p. Furthermore, in vivo xenograft models were established to further investigate the intrinsic role of miR-199a-5p in osteosarcoma tumorigenesis and angiogenesis. Results: A total of 149 DE-miRNAs were screened out, including 136 upregulated miRNAs and 13 downregulated miRNAs in human osteosarcoma plasma samples compared with normal plasma samples. A total of 1313 target genes of the top three upregulated and downregulated miRNAs were predicted. In the PPI network, the top 10 hub nodes with higher degrees were identified as hub genes, such as TP53 and VEGFA. By constructing the miRNA-hub gene network, we found that most of hub genes could be potentially modulated by miR-663a, miR-199a-5p and miR-223-3p. In addition, we found that the expression level of miR-199a-5p in exosomes derived from osteosarcoma cells was remarkably higher than the osteosarcoma cells, and the exosomes derived from osteosarcoma cells were transported to HUVECs. Overexpression of miR-199a-5p could significantly inhibited HUVEC proliferation, migration and neovascularization, whereas downregulation of miR-199a-5p expression exerted the opposite effect. Moreover, the in vivo results verified that overexpression of miR-199a-5p in osteosarcoma cells could suppress the growth and angiogenesis of tumors. Conclusion: Our results demonstrated that miR-199a-5p could be transported from osteosarcoma cells to HUVECs through exosomes, subsequently targeting VEGFA and inhibiting the growth and angiogenesis of osteosarcoma. Therefore, miR-199a-5p may act as a biomarker in the diagnosis and treatment of osteosarcoma.

scholarly journals Interdependent transcription control elements regulate the expression of the SPRR2A gene during keratinocyte terminal differentiation.

1996 ◽  
Vol 16 (10) ◽  
pp. 5365-5374 ◽  
Author(s):  
D F Fischer ◽  
S Gibbs ◽  
P van De Putte ◽  
C Backendorf
Keyword(s):  
Transcription Factors ◽  
Molecular Mechanisms ◽  
Terminal Differentiation ◽  
Site Directed Mutagenesis ◽  
Deletion Mapping ◽  
Transcription Control ◽  
Mobility Shift ◽  
Response Element

Expression of the SPRR2A gene, a member of the small proline-rich family of cornified cell envelope precursor proteins, is strictly linked to keratinocyte terminal differentiation both in vivo and in vitro. In this study, we explored the molecular mechanisms underlying this regulation in transiently transfected primary keratinocytes induced to differentiate in vitro. Deletion mapping and site-directed mutagenesis of SPRR2A promoter-chloramphenicol acetyltransferase constructs indicate that four transcription control elements are essential and sufficient for promoter activity. These elements were further characterized by electrophoretic mobility shift and identified as (i) an inverted octamer doublet, bound by the POU domain factor Oct-11 (Skn-1a/i, Epoc-1), (ii) an interferon-stimulated response element recognized by interferon regulatory factors 1 and 2, (iii) an Ets binding site partially overlapping the interferon-stimulated response element, and (iv) a TG box recognized by the Sp1 family of zinc finger transcription factors. Destruction of a single terminal differentiation element is sufficient to completely abolish transcription from the SPRR2A promoter, indicating that these transcription control elements function in concert in an interdependent manner. Apparently, integration of signals transmitted by the above-mentioned transcription factors is necessary and sufficient to promote gene expression during keratinocyte terminal differentiation.

scholarly journals POS0400 METABOLIC CHANGES INDUCED BY ANTI-MALONDIALDEHYDE/MALINDIALDEHYDE-ACETALDEHYDE ANTIBODIES PROMOTE OSTEOCLAST DEVELOPMENT

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 429-429
Author(s):  
K. Sakuraba ◽  
A. Krishnamurthy ◽  
A. Circiumaru ◽  
V. Joshua ◽  
H. Wähämaa ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Bone Loss ◽  
Molecular Mechanisms ◽  
Cellular Metabolism ◽  
Tca Cycle ◽  
Tartrate Resistant Acid Phosphatase ◽  
Fcγ Receptor ◽  
Research Support

Background:Malondialdehyde (MDA) is a highly reactive compound generated during lipid-peroxidation in conditions associated with oxidative stress. MDA can irreversibly modify proteins (e.g. lysine, arginine and histidine residues). In addition, acetaldehyde can further react with MDA adducts to form malondialdehyde-acetaldehyde (MAA) modification. Such protein modifications can lead to immunogenic neo-epitopes that are recognized by autoantibodies. In fact, anti-MDA/MAA IgG antibodies are significantly increased in the serum of patients with autoimmune diseases, such as rheumatoid arthritis (RA) (1). Interestingly, anti-MDA/MAA antibodies have been shown to promote osteoclast (OC) differentiation in vitro suggesting a potential role for these autoantibodies in bone damage associated with RA (1).Objectives:Little is known about the molecular mechanisms activated by autoantibodies in RA. Here, we elucidate the pathways specifically triggered by anti-MDA/MAA autoantibodies in developing osteoclasts.Methods:Recombinant human monoclonal anti-MDA/MAA antibodies, which were previously cloned from single synovial B cells of RA patients, were added to different OC assays. OCs were generated from monocyte-derived macrophages in the presence of the cytokines RANK-L and M-CSF. OC development was monitored by light microscopy following tartrate-resistant acid phosphatase staining and by erosion assays using calcium phosphate-coated plates. Bone morphometrics were studied in anti-MDA/MAA-injected mice using X-ray microscopy. Cellular metabolism was analyzed by mass spectrometry, Seahorse XF Analyzer and a colorimetric L-Lactate assay.Results:Anti-MDA/MAA antibodies induced a robust OC differentiation in vitro and bone loss in vivo. The anti-MDA/MAA antibodies acted on developing OCs by increasing glycolysis via an Fcγ receptor I-mediated pathway and the upregulation of the transcription factors HIF-1α, Myc and CHREBP. Such regulation of cellular metabolism was exclusively observed in the presence of the osteoclastogenic anti-MDA/MAA clones, whereas other RA-associated autoantibodies (anti-MDA/MAA or anti-citrullinated protein antibodies) had no effect on metabolism. The anti-MDA/MAA treatment induced a shift in the tricarboxylic acid (TCA) cycle activity in developing OCs, leading to the accumulation of citrate and aconitate.Conclusion:We described a novel type of autoantibody-induced pathway in RA, which might contribute to increased OC activation and a consequent bone loss. Anti-MDA/MAA antibodies promoted osteoclast development by increasing glycolysis and by modulating the TCA cycle through a signaling pathway that included Fcγ receptor I and a network of transcription factors acting on glycolysis. A TCA cycle bias towards citrate production suggests that the anti-MDA/MAA antibodies might stimulate OCs via increasing lipid biosynthesis in the cells.References:[1]Grönwall C. et al. J. Autoimmunity 84 (2017): 29-45.Acknowledgements:This Project has received funding from FOREUM, Foundation for Research in Rheumatology, from the European Research Council (ERC) grant agreement CoG 2017 - 7722209_PREVENT RA, the EU/EFPIA Innovative Medicine Initiative grant agreement 777357_RTCure, the Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse and Knut and Alice Wallenberg Foundation.Disclosure of Interests:Koji Sakuraba: None declared, Akilan Krishnamurthy: None declared, Alexandra Circiumaru: None declared, Vijay Joshua: None declared, Heidi Wähämaa: None declared, Marianne Engström: None declared, Meng Sun: None declared, Xiaowei Zheng: None declared, Cheng Xu: None declared, Khaled Amara: None declared, Vivianne Malmström Grant/research support from: collaboration with Pfizer, unrelated to the abstract, Sergiu-Bogdan Catrina: None declared, Caroline Grönwall: None declared, Bence Réthi: None declared, Anca Catrina Grant/research support from: collaboration with BMS and Pfizer, unrelated to the present abstract

scholarly journals Combination of Systems Pharmacology and Experimental Evaluation to Explore the Mechanism of Synergistic Action of Frankincense-Myrrh in the Treatment of Cerebrovascular Diseases

2022 ◽  
Vol 12 ◽  
Author(s):  
Yucheng Liao ◽  
Jingwen Wang ◽  
Chao Guo ◽  
Min Bai ◽  
Bowei Ju ◽  
...  
Keyword(s):  
Target Genes ◽  
Inflammatory Responses ◽  
Infarct Volume ◽  
Blood Stasis ◽  
Enrichment Analysis ◽  
Cerebrovascular Diseases ◽  
Pathway Enrichment Analysis ◽  
Systems Pharmacology

Frankincense-Myrrh is a classic drug pair that promotes blood circulation, and eliminates blood stasis. The combination of the two drugs has a definite clinical effect on the treatment of cerebrovascular diseases (CBVDs), but its mechanism of action and compatibility have not been elucidated. In this study, the bioactive components, core targets, and possible synergistic mechanisms of Frankincense-Myrrh in the treatment of CBVDs are explored through systems pharmacology combined with in vivo and in vitro experiments. Comparing target genes of components in Frankincense and Myrrh with CBVD-related genes, common genes were identified; 15 core target genes of Frankincense-Myrrh for the treatment of CBVDs were then identified using protein-protein interaction (PPI) analysis. It was also predicted through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis that the molecular mechanism of Frankincense-Myrrh action on CBVDs was mainly related to the regulation of neurotrophic factors and inflammatory responses. Frankincense-Myrrh significantly improved neurological function, decreased infarct volume, alleviated histopathological damage, inhibited microglial expression, and promoted the expression of neurons in middle cerebral artery occlusion (MCAO)-induced rats. The results of this study not only provide important theoretical support and experimental basis for the synergistic effect of Frankincense-Myrrh, but also provide new ideas for the prevention and treatment of cerebral ischemic injuries.

scholarly journals Network Pharmacology-Based Prediction of the Active Ingredients and Potential Targets of Chinese Herbal Danyu Gukang Pills for Application to Osteonecrosis of the Femoral Head Disease

2021 ◽  
Author(s):  
Yongchang Guo ◽  
Dapeng Zhang ◽  
Yuju Cao ◽  
Xiaoyan Feng ◽  
Caihong Shen ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Femoral Head ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
In Vitro Experiments ◽  
Active Components

Abstract Ethnopharmacological relevanceOsteonecrosis of the femoral head (ONFH) is still a challenge for orthopedists worldwide, which may lead to disability in patients without effective treatment. A newly developed formula of Chinese medicine, Danyu Gukang Pills (DGP), was recognized to be effective for ONFH. Nevertheless, its molecular mechanisms remain to be clarified. MethodsNetwork pharmacology was adopted to detect the mechanism of DGP on ONFH. The compounds of DGP were collected from the online databases, and active components were selected based on their OB and DL index. The potential proteins of DGP were acquired from TCMSP database, while the potential genes of ONFH were obtained from Gene Cards and Pubmed Gene databases. The function of Gene and potential pathways were researched by GO and KEGG pathway enrichment analysis. The compounds-targets and targets-pathways network were constructed in an R and Cytosacpe software. The mechanism was further investigated via molecular docking. Finally, in-vitro experiments were validated in the BMSCs. ResultsA total of 2305 compounds in DGP were gained, among which, 370 were selected as active components for which conforming to criteria. Combined the network analysis, molecular docking and in-vitro experiments, the results firstly demonstrated that the treatment effect of DGP on ONFH may be closely related to HIF-1α, VEGFA and HIF-1 signaling pathway. ConclusionThe current study firstly researched the molecular mechanism of DGP on ONFH based on network pharmacology. The results indicated that DGP may exert the effect on ONFH targeting on HIF-1α and VEGFA via HIF-1 signaling pathway.

scholarly journals Upregulation of FEN1 Is Associated with the Tumor Progression and Prognosis of Hepatocellular Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Yingying Zhang ◽  
Xin Liu ◽  
Liwen Liu ◽  
Jianan Chen ◽  
Qiuyue Hu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Cox Regression ◽  
Malignant Tumors ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Functional Roles ◽  
Protein Levels ◽  
And Migration

Background. Studies show that patients with hepatocellular carcinoma (HCC) have poor prognosis, particularly when patients are diagnosed at late stages of the disease development. The flap endonuclease 1 (FEN1) gene is overexpressed in multiple malignant tumors and may promote tumor aggressiveness. However, its expression profile and functional roles in HCC are still unclear. Here, we evaluated the molecular mechanisms of FEN1 in HCC. Methods. The expression of FEN1 in HCC was evaluated using HCC mRNA expression data from TCGA and GEO databases. The expression of FEN1 was also confirmed by immunohistochemistry (IHC) using a tissue microarray (TMA) cohort with a total of 396 HCC patients. Kaplan-Meier analysis and univariate and multivariate Cox regression analyses were used to determine the correlation between FEN1 expression and survival rate of HCC patients. The molecular mechanism and biological functions of FEN1 in HCC were predicted using functional and pathway enrichment analysis in vitro experiments. Results. FEN1 was overexpressed in multiple HCC cohorts at both mRNA and protein levels. The receiver operating characteristic (ROC) curve showed that FEN1 can serve as a diagnostic predictor of HCC. Meanwhile, patients with high FEN1 expression levels showed lower overall survival (OS) and relapse-free survival (RFS) rates than those with low FEN1 expression. More importantly, we found that FEN1 elevation was an independent prognostic factor for OS and RFS in HCC patients based on univariate and multivariate analyses, indicating that FEN1 might be a potential prognostic marker in HCC. Furthermore, knocking down FEN1 resulted in suppressed cell proliferation and migration in vitro. This could have been due to regulation expressions of c-Myc, survivin, and cyclin D1 genes, indicating that FEN1 may function as an oncogene through its role in the cell cycle and DNA replication pathway. Conclusion. Our study indicated that high FEN1 expression might function as a biomarker for diagnosis and prognosis. In addition, the study confirms that FEN1 is an oncogene in HCC progression.

scholarly journals SOX2 and BRN2 as Key Transcription Factors in Neural Rosette Formation In Vitro

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Zuzana Hudáčová ◽  
Keyword(s):  
Transcription Factors ◽  
Neural Development ◽  
Molecular Mechanisms ◽  
Rosette Formation ◽  
In Vivo Studies ◽  
Confounding Variables ◽  
Vitro Model ◽  
Underlying Processes

Although neurogenesis has been well studied, its molecular mechanisms remain largely unknown due to the challenges posed by the complexity of the underlying processes. Whilst in vivo studies can be used to study neurogenesis, the inability to control confounding variables complicate findings. Therefore, the purpose of this study was to identify the markers of in vitro neural rosette formation and describe the formation of neural rosettes from pluripotent stem cells using immunofluorescence analysis. The protocol of stem cell cultivation and induction of neural rosette formation was tested. Following, two transcription factors, BRN2 and SOX2, were fluorescently labelled and cells were imaged over a period of eight days. It was identified that SOX2 and BRN2 are expressed during in vitro neural rosette formation. These results are concurrent with in vivo neurogenesis, which suggests that neural rosettes could be a suitable in vitro model for researching neural development. Given that mistakes can arise during neurogenesis, such as neural tube defects, developing robust models to understand the formation of the nervous system is important. Moving forward, a detailed molecular understanding of neural rosette formation has the potential to be used for targeting specific transcription factors to treat or prevent problematic neurogenesis.

scholarly journals A cutting-edge approach unravels a novel role for CDK6 in leukemic progenitor cells

2020 ◽  
Author(s):  
Eszter Doma ◽  
Isabella Maria Mayer ◽  
Tania Brandstoetter ◽  
Barbara Maurer ◽  
Reinhard Grausenburger ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Cell Lines ◽  
Progenitor Cell ◽  
Molecular Mechanisms ◽  
List Type ◽  
Robust Method ◽  
Cell Homing ◽  
Key Points

AbstractStudies of molecular mechanisms of hematopoiesis and leukemogenesis are hampered by the unavailability of progenitor cell lines that accurately mimic the situation in vivo. We now report a robust method to generate and maintain LSK (lin-, Sca-1+, c-Kit+) cells which closely resemble MPP1 cells. HPCLSK reconstitute hematopoiesis in lethally irradiated recipient mice over more than eight months. Upon transformation with different oncogenes including BCR/ABL, FLT3-ITD or MLL-AF9 their leukemic counterparts maintain stem cell properties in vitro and recapitulate leukemia formation in vivo. The method to generate HPCLSK can be applied to transgenic mice and we illustrate it for CDK6-deficient animals. Upon BCR/ABLp210 transformation, Cdk6-/- HPCLSKs induce disease with a significantly enhanced latency and reduced incidence, showing the importance of CDK6 in leukemia formation. Studies of the CDK6 transcriptome in murine HPCLSK and human BCR/ABL+ cells have verified that certain pathways depend on CDK6 and have uncovered a novel CDK6-dependent signature, suggesting a role for CDK6 in leukemic progenitor cell homing. Loss of CDK6 may thus lead to a defect in homing. The HPCLSK system represents a unique tool for combined in vitro and in vivo studies and enables the production of large quantities of genetically modifiable hematopoietic or leukemic stem/progenitor cells.Key pointsWe describe the generation of murine cell lines (HPCLSK) which reliably mimic hematopoietic/leukemic progenitor cells.Cdk6-/- BCR/ABLp210 HPCLSKs uncover a novel role for CDK6 in homing.

Differential impact of rhamnolipids and polysorbate80 on composition and functionality of the gut microbiota in the SHIME system.

2021 ◽  
Author(s):  
Lisa Miclotte ◽  
Ellen De Paepe ◽  
Qiqiong Li ◽  
Andreja Rajkovic ◽  
John Van Camp ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Enrichment Analysis ◽  
Human Colon ◽  
Pathway Enrichment Analysis ◽  
Analysis Tool ◽  
Longitudinal Impact ◽  
Cell Counts ◽  
The Impact

Dietary emulsifiers have been shown to affect the composition and function of the gut microbial community, both in vivo and in vitro. Yet, several knowledge gaps remain to be addressed: the impact from a longer timeframe exposure on the gut microbiota, interindividual variability in microbiome response and the putative impact from novel clean label alternatives for current food emulsifiers. In the present study, the impact of one conventional dietary emulsifier, TWEEN80, and one potential novel alternative, rhamnolipids, on the human gut microbiota was investigated using the Mucosal Simulator of the Human Intestinal Microbial Ecosystem (M-SHIME). The faecal microbiota from two human donors, with high and low responsiveness to the emulsifiers, were exposed to 0,05 m% and 0,5 m% of the emulsifiers for 7 days. The results confirmed previous observations that the effects on the composition and functionality are both emulsifier- and donor dependent. The effects reached an equilibrium after about 3 days of exposure. Overall, TWEEN80 and rhamnolipids displayed opposite effects: TWEEN80 increased cell counts, reduced propionate concentration, increased butyrate levels, increased a.o. Faecalibacterium, Blautia and Hungatella abundance, while rhamnolipids did the opposite. Rhamnolipids also sharply increased the abundance of unclassified Lachnospiraceae. On the other hand, both emulsifiers increased the relative abundance of unclassified Enterobacteriaceae. Both emulsifiers also altered the microbial metabolome in different ways and a pathway enrichment analysis tool revealed that the metabolome alterations could be reminiscent of gut issues and obesity. Overall, the impact from the rhamnolipids was larger than that of TWEEN80 at similar concentrations, indicating that the former may not necessarily be a safer alternative for the latter. The response of the microbiota also depended on its original composition and the sensitivity status for which the faecal donors were selected, was preserved. Whether the same donor-diversity and longitudinal impact can be expected in the human colon as well and what impact this has on the host will have to be further investigated.

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