In Vitro Screening for Probiotic Properties of <i>Lactobacillus</i> and <i>Bifidobacterium</i> Strains in Assays Relevant for Non-Alcoholic Fatty Liver Disease Prevention
Non-alcoholic fatty liver disease (NAFLD) is a multifactorial metabolic disorder that poses health challenges worldwide and is expected to continue to rise dramatically. NAFLD is associated with metabolic syndrome, type 2 diabetes mellitus, and impaired gut health. Increased gut permeability, caused...
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| Format: | Article |
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MDPI AG
2023-05-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/15/10/2361 |
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| author | Silvia Lopez-Escalera Mari L. Lund Gerben D. A. Hermes Béatrice S.-Y. Choi Kei Sakamoto Anja Wellejus |
| author_facet | Silvia Lopez-Escalera Mari L. Lund Gerben D. A. Hermes Béatrice S.-Y. Choi Kei Sakamoto Anja Wellejus |
| author_sort | Silvia Lopez-Escalera |
| collection | DOAJ |
| description | Non-alcoholic fatty liver disease (NAFLD) is a multifactorial metabolic disorder that poses health challenges worldwide and is expected to continue to rise dramatically. NAFLD is associated with metabolic syndrome, type 2 diabetes mellitus, and impaired gut health. Increased gut permeability, caused by disturbance of tight junction proteins, allows passage of damaging microbial components that, upon reaching the liver, have been proposed to trigger the release of inflammatory cytokines and generate cellular stress. A growing body of research has suggested the utilization of targeted probiotic supplements as a preventive therapy to improve gut barrier function and tight junctions. Furthermore, specific microbial interactions and metabolites induce the secretion of hormones such as GLP-1, resulting in beneficial effects on liver health. To increase the likelihood of finding beneficial probiotic strains, we set up a novel screening platform consisting of multiple in vitro and ex vivo assays for the screening of 42 bacterial strains. Analysis of transepithelial electrical resistance response via co-incubation of the 42 bacterial strains with human colonic cells (Caco-2) revealed improved barrier integrity. Then, strain-individual metabolome profiling was performed revealing species-specific clusters. GLP-1 secretion assay with intestinal secretin tumor cell line (STC-1) found at least seven of the strains tested capable of enhancing GLP-1 secretion in vitro. Gene expression profiling in human biopsy-derived intestinal organoids was performed using next generation sequencing transcriptomics post bacterial co-incubation. Here, different degrees of immunomodulation by the increase in certain cytokine and chemokine transcripts were found. Treatment of mouse primary hepatocytes with selected highly produced bacterial metabolites revealed that indole metabolites robustly inhibited de novo lipogenesis. Collectively, through our comprehensive bacterial screening pipeline, not previously ascribed strains from both Lactobacillus and Bifidobacterium genera were proposed as potential probiotics based on their ability to increase epithelial barrier integrity and immunity, promote GLP-1 secretion, and produce metabolites relevant to liver health. |
| first_indexed | 2024-03-11T03:25:15Z |
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| id | doaj.art-37414f7b9f004cffa534e50917171fb1 |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-11T03:25:15Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-37414f7b9f004cffa534e50917171fb12023-11-18T02:45:19ZengMDPI AGNutrients2072-66432023-05-011510236110.3390/nu15102361In Vitro Screening for Probiotic Properties of <i>Lactobacillus</i> and <i>Bifidobacterium</i> Strains in Assays Relevant for Non-Alcoholic Fatty Liver Disease PreventionSilvia Lopez-Escalera0Mari L. Lund1Gerben D. A. Hermes2Béatrice S.-Y. Choi3Kei Sakamoto4Anja Wellejus5Human Health Research, Scientific Affairs, Chr. Hansen A/S, Bøge Alle 10-12, 2970 Hørsholm, DenmarkHuman Health Research, Scientific Affairs, Chr. Hansen A/S, Bøge Alle 10-12, 2970 Hørsholm, DenmarkHuman Health Research, Scientific Affairs, Chr. Hansen A/S, Bøge Alle 10-12, 2970 Hørsholm, DenmarkDepartment of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, 2200 Copenhagen, DenmarkHuman Health Research, Scientific Affairs, Chr. Hansen A/S, Bøge Alle 10-12, 2970 Hørsholm, DenmarkNon-alcoholic fatty liver disease (NAFLD) is a multifactorial metabolic disorder that poses health challenges worldwide and is expected to continue to rise dramatically. NAFLD is associated with metabolic syndrome, type 2 diabetes mellitus, and impaired gut health. Increased gut permeability, caused by disturbance of tight junction proteins, allows passage of damaging microbial components that, upon reaching the liver, have been proposed to trigger the release of inflammatory cytokines and generate cellular stress. A growing body of research has suggested the utilization of targeted probiotic supplements as a preventive therapy to improve gut barrier function and tight junctions. Furthermore, specific microbial interactions and metabolites induce the secretion of hormones such as GLP-1, resulting in beneficial effects on liver health. To increase the likelihood of finding beneficial probiotic strains, we set up a novel screening platform consisting of multiple in vitro and ex vivo assays for the screening of 42 bacterial strains. Analysis of transepithelial electrical resistance response via co-incubation of the 42 bacterial strains with human colonic cells (Caco-2) revealed improved barrier integrity. Then, strain-individual metabolome profiling was performed revealing species-specific clusters. GLP-1 secretion assay with intestinal secretin tumor cell line (STC-1) found at least seven of the strains tested capable of enhancing GLP-1 secretion in vitro. Gene expression profiling in human biopsy-derived intestinal organoids was performed using next generation sequencing transcriptomics post bacterial co-incubation. Here, different degrees of immunomodulation by the increase in certain cytokine and chemokine transcripts were found. Treatment of mouse primary hepatocytes with selected highly produced bacterial metabolites revealed that indole metabolites robustly inhibited de novo lipogenesis. Collectively, through our comprehensive bacterial screening pipeline, not previously ascribed strains from both Lactobacillus and Bifidobacterium genera were proposed as potential probiotics based on their ability to increase epithelial barrier integrity and immunity, promote GLP-1 secretion, and produce metabolites relevant to liver health.https://www.mdpi.com/2072-6643/15/10/2361probioticslactobacillusbifidobacteriumNAFLDgut healthGLP-1 |
| spellingShingle | Silvia Lopez-Escalera Mari L. Lund Gerben D. A. Hermes Béatrice S.-Y. Choi Kei Sakamoto Anja Wellejus In Vitro Screening for Probiotic Properties of <i>Lactobacillus</i> and <i>Bifidobacterium</i> Strains in Assays Relevant for Non-Alcoholic Fatty Liver Disease Prevention Nutrients probiotics lactobacillus bifidobacterium NAFLD gut health GLP-1 |
| title | In Vitro Screening for Probiotic Properties of <i>Lactobacillus</i> and <i>Bifidobacterium</i> Strains in Assays Relevant for Non-Alcoholic Fatty Liver Disease Prevention |
| title_full | In Vitro Screening for Probiotic Properties of <i>Lactobacillus</i> and <i>Bifidobacterium</i> Strains in Assays Relevant for Non-Alcoholic Fatty Liver Disease Prevention |
| title_fullStr | In Vitro Screening for Probiotic Properties of <i>Lactobacillus</i> and <i>Bifidobacterium</i> Strains in Assays Relevant for Non-Alcoholic Fatty Liver Disease Prevention |
| title_full_unstemmed | In Vitro Screening for Probiotic Properties of <i>Lactobacillus</i> and <i>Bifidobacterium</i> Strains in Assays Relevant for Non-Alcoholic Fatty Liver Disease Prevention |
| title_short | In Vitro Screening for Probiotic Properties of <i>Lactobacillus</i> and <i>Bifidobacterium</i> Strains in Assays Relevant for Non-Alcoholic Fatty Liver Disease Prevention |
| title_sort | in vitro screening for probiotic properties of i lactobacillus i and i bifidobacterium i strains in assays relevant for non alcoholic fatty liver disease prevention |
| topic | probiotics lactobacillus bifidobacterium NAFLD gut health GLP-1 |
| url | https://www.mdpi.com/2072-6643/15/10/2361 |
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