Metagenomic signatures reveal the key role of phloretin in amelioration of gut dysbiosis attributed to metabolic dysfunction-associated fatty liver disease by time-dependent modulation of gut microbiome
The importance of gut-liver axis in the pathophysiology of metabolic dysfunction-associated fatty liver disease (MAFLD) is being investigated more closely in recent times. However, the inevitable changes in gut microbiota during progression of the disease merits closer look. The present work intends...
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1210517/full |
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| author | Jyoti Chhimwal Jyoti Chhimwal Prince Anand Prince Anand Priyanka Mehta Priyanka Mehta Mohit Kumar Swarnkar Vikram Patial Vikram Patial Rajesh Pandey Rajesh Pandey Yogendra Padwad Yogendra Padwad |
| author_facet | Jyoti Chhimwal Jyoti Chhimwal Prince Anand Prince Anand Priyanka Mehta Priyanka Mehta Mohit Kumar Swarnkar Vikram Patial Vikram Patial Rajesh Pandey Rajesh Pandey Yogendra Padwad Yogendra Padwad |
| author_sort | Jyoti Chhimwal |
| collection | DOAJ |
| description | The importance of gut-liver axis in the pathophysiology of metabolic dysfunction-associated fatty liver disease (MAFLD) is being investigated more closely in recent times. However, the inevitable changes in gut microbiota during progression of the disease merits closer look. The present work intends to assess the time-dependent gut dysbiosis in MAFLD, its implications in disease progression and role of plant-derived prebiotics in its attenuation. Male C57BL/6J mice were given western diet (WD) for up to 16 weeks and phloretin was administered orally. The fecal samples of mice were collected every fourth week for 16 weeks. The animals were sacrificed at the end of the study and biochemical and histological analyses were performed. Further, 16S rRNA amplicon sequencing analysis was performed to investigate longitudinal modification of gut microbiome at different time points. Findings of our study corroborate that phloretin alleviated the metabolic changes and mitigated circulating inflammatory cytokines levels. Phloretin treatment resists WD induced changes in microbial diversity of mice and decreased endotoxin content. Prolonged exposure of WD changed dynamics of gut microbiota abundance and distribution. Increased abundance of pathogenic taxa like Desulfovibrionaceae, Peptostreptococcus, Clostridium, and Terrisporobacter was noted. Phloretin treatment not only reversed this dysbiosis but also modulated taxonomic signatures of beneficial microbes like Ruminococcus, Lactobacillus, and Alloprevotella. Therefore, the potential of phloretin to restore gut eubiosis could be utilized as an intervention strategy for the prevention of MAFLD and related metabolic disorders. |
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| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-03-12T02:02:10Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-63091983d1a54b0ba3a80e44f0ac5e222023-09-07T11:32:27ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2023-09-011410.3389/fmicb.2023.12105171210517Metagenomic signatures reveal the key role of phloretin in amelioration of gut dysbiosis attributed to metabolic dysfunction-associated fatty liver disease by time-dependent modulation of gut microbiomeJyoti Chhimwal0Jyoti Chhimwal1Prince Anand2Prince Anand3Priyanka Mehta4Priyanka Mehta5Mohit Kumar Swarnkar6Vikram Patial7Vikram Patial8Rajesh Pandey9Rajesh Pandey10Yogendra Padwad11Yogendra Padwad12Pharmacology and Toxicology Laboratory, Dietetics and Nutrition Technology Division, CSIR-Institute of Himalayan Bioresource Technology (CSIR-IHBT), Palampur, IndiaAcademy of Scientific and Innovative Research (AcSIR), Ghaziabad, IndiaPharmacology and Toxicology Laboratory, Dietetics and Nutrition Technology Division, CSIR-Institute of Himalayan Bioresource Technology (CSIR-IHBT), Palampur, IndiaAcademy of Scientific and Innovative Research (AcSIR), Ghaziabad, IndiaAcademy of Scientific and Innovative Research (AcSIR), Ghaziabad, IndiaINtegrative GENomics of HOst-PathogEn (INGEN-HOPE) Laboratory, CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB), New Delhi, IndiaBiotechnology Division, CSIR-Institute of Himalayan Bioresource Technology (CSIR-IHBT), Palampur, IndiaPharmacology and Toxicology Laboratory, Dietetics and Nutrition Technology Division, CSIR-Institute of Himalayan Bioresource Technology (CSIR-IHBT), Palampur, IndiaAcademy of Scientific and Innovative Research (AcSIR), Ghaziabad, IndiaAcademy of Scientific and Innovative Research (AcSIR), Ghaziabad, IndiaINtegrative GENomics of HOst-PathogEn (INGEN-HOPE) Laboratory, CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB), New Delhi, IndiaPharmacology and Toxicology Laboratory, Dietetics and Nutrition Technology Division, CSIR-Institute of Himalayan Bioresource Technology (CSIR-IHBT), Palampur, IndiaAcademy of Scientific and Innovative Research (AcSIR), Ghaziabad, IndiaThe importance of gut-liver axis in the pathophysiology of metabolic dysfunction-associated fatty liver disease (MAFLD) is being investigated more closely in recent times. However, the inevitable changes in gut microbiota during progression of the disease merits closer look. The present work intends to assess the time-dependent gut dysbiosis in MAFLD, its implications in disease progression and role of plant-derived prebiotics in its attenuation. Male C57BL/6J mice were given western diet (WD) for up to 16 weeks and phloretin was administered orally. The fecal samples of mice were collected every fourth week for 16 weeks. The animals were sacrificed at the end of the study and biochemical and histological analyses were performed. Further, 16S rRNA amplicon sequencing analysis was performed to investigate longitudinal modification of gut microbiome at different time points. Findings of our study corroborate that phloretin alleviated the metabolic changes and mitigated circulating inflammatory cytokines levels. Phloretin treatment resists WD induced changes in microbial diversity of mice and decreased endotoxin content. Prolonged exposure of WD changed dynamics of gut microbiota abundance and distribution. Increased abundance of pathogenic taxa like Desulfovibrionaceae, Peptostreptococcus, Clostridium, and Terrisporobacter was noted. Phloretin treatment not only reversed this dysbiosis but also modulated taxonomic signatures of beneficial microbes like Ruminococcus, Lactobacillus, and Alloprevotella. Therefore, the potential of phloretin to restore gut eubiosis could be utilized as an intervention strategy for the prevention of MAFLD and related metabolic disorders.https://www.frontiersin.org/articles/10.3389/fmicb.2023.1210517/fullgut microbiomeMAFLDphloretin16S rRNAmetagenome |
| spellingShingle | Jyoti Chhimwal Jyoti Chhimwal Prince Anand Prince Anand Priyanka Mehta Priyanka Mehta Mohit Kumar Swarnkar Vikram Patial Vikram Patial Rajesh Pandey Rajesh Pandey Yogendra Padwad Yogendra Padwad Metagenomic signatures reveal the key role of phloretin in amelioration of gut dysbiosis attributed to metabolic dysfunction-associated fatty liver disease by time-dependent modulation of gut microbiome Frontiers in Microbiology gut microbiome MAFLD phloretin 16S rRNA metagenome |
| title | Metagenomic signatures reveal the key role of phloretin in amelioration of gut dysbiosis attributed to metabolic dysfunction-associated fatty liver disease by time-dependent modulation of gut microbiome |
| title_full | Metagenomic signatures reveal the key role of phloretin in amelioration of gut dysbiosis attributed to metabolic dysfunction-associated fatty liver disease by time-dependent modulation of gut microbiome |
| title_fullStr | Metagenomic signatures reveal the key role of phloretin in amelioration of gut dysbiosis attributed to metabolic dysfunction-associated fatty liver disease by time-dependent modulation of gut microbiome |
| title_full_unstemmed | Metagenomic signatures reveal the key role of phloretin in amelioration of gut dysbiosis attributed to metabolic dysfunction-associated fatty liver disease by time-dependent modulation of gut microbiome |
| title_short | Metagenomic signatures reveal the key role of phloretin in amelioration of gut dysbiosis attributed to metabolic dysfunction-associated fatty liver disease by time-dependent modulation of gut microbiome |
| title_sort | metagenomic signatures reveal the key role of phloretin in amelioration of gut dysbiosis attributed to metabolic dysfunction associated fatty liver disease by time dependent modulation of gut microbiome |
| topic | gut microbiome MAFLD phloretin 16S rRNA metagenome |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1210517/full |
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