Spatial variation of the gut microbiome in response to long-term metformin treatment in high-fat diet-induced type 2 diabetes mouse model of both sexes

ABSTRACTAntidiabetic drug metformin alters the gut microbiome composition in the context of type 2 diabetes and other diseases; however, its effects have been mainly studied using fecal samples, which offer limited information about the intestinal site-specific effects of this drug. Our study aimed...

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Main Authors: Laila Silamiķele, Rihards Saksis, Ivars Silamiķelis, Patrīcija Paulīne Kotoviča, Monta Brīvība, Ineta Kalniņa, Zane Kalniņa, Dāvids Fridmanis, Jānis Kloviņš
Format: Article
Language:English
Published: Taylor & Francis Group 2023-12-01
Series:Gut Microbes
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/19490976.2023.2188663
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author Laila Silamiķele
Rihards Saksis
Ivars Silamiķelis
Patrīcija Paulīne Kotoviča
Monta Brīvība
Ineta Kalniņa
Zane Kalniņa
Dāvids Fridmanis
Jānis Kloviņš
author_facet Laila Silamiķele
Rihards Saksis
Ivars Silamiķelis
Patrīcija Paulīne Kotoviča
Monta Brīvība
Ineta Kalniņa
Zane Kalniņa
Dāvids Fridmanis
Jānis Kloviņš
author_sort Laila Silamiķele
collection DOAJ
description ABSTRACTAntidiabetic drug metformin alters the gut microbiome composition in the context of type 2 diabetes and other diseases; however, its effects have been mainly studied using fecal samples, which offer limited information about the intestinal site-specific effects of this drug. Our study aimed to characterize the spatial variation of the gut microbiome in response to metformin treatment by using a high-fat diet-induced type 2 diabetes mouse model of both sexes. Four intestinal parts, each at the luminal and mucosal layer level, were analyzed in this study by performing 16S rRNA sequencing covering six variable regions (V1-V6) of the gene and thus allowing to obtain in-depth information about the microbiome composition. We identified significant differences in gut microbiome diversity in each of the intestinal parts regarding the alpha and beta diversities. Metformin treatment altered the abundance of different genera in all studied intestinal sites, with the most pronounced effect in the small intestine, where Lactococcus increased remarkably. The abundance of Lactobacillus was substantially lower in male mice compared to female mice in all locations, in addition to an enrichment of opportunistic pathogens. Diet type and intestinal layer had significant effects on microbiome composition at each of the sites studied. We observed a different effect of metformin treatment on the analyzed subsets, indicating the multiple dimensions of metformin’s effect on the gut microbiome.
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spelling doaj.art-4a64372d4ca04d9dbf5867275cf171402024-03-28T22:38:20ZengTaylor & Francis GroupGut Microbes1949-09761949-09842023-12-0115110.1080/19490976.2023.2188663Spatial variation of the gut microbiome in response to long-term metformin treatment in high-fat diet-induced type 2 diabetes mouse model of both sexesLaila Silamiķele0Rihards Saksis1Ivars Silamiķelis2Patrīcija Paulīne Kotoviča3Monta Brīvība4Ineta Kalniņa5Zane Kalniņa6Dāvids Fridmanis7Jānis Kloviņš8Human genetics and disease mechanisms, Latvian Biomedical Research and Study Centre, Riga, LatviaHuman genetics and disease mechanisms, Latvian Biomedical Research and Study Centre, Riga, LatviaHuman genetics and disease mechanisms, Latvian Biomedical Research and Study Centre, Riga, LatviaHuman genetics and disease mechanisms, Latvian Biomedical Research and Study Centre, Riga, LatviaHuman genetics and disease mechanisms, Latvian Biomedical Research and Study Centre, Riga, LatviaHuman genetics and disease mechanisms, Latvian Biomedical Research and Study Centre, Riga, LatviaHuman genetics and disease mechanisms, Latvian Biomedical Research and Study Centre, Riga, LatviaHuman genetics and disease mechanisms, Latvian Biomedical Research and Study Centre, Riga, LatviaHuman genetics and disease mechanisms, Latvian Biomedical Research and Study Centre, Riga, LatviaABSTRACTAntidiabetic drug metformin alters the gut microbiome composition in the context of type 2 diabetes and other diseases; however, its effects have been mainly studied using fecal samples, which offer limited information about the intestinal site-specific effects of this drug. Our study aimed to characterize the spatial variation of the gut microbiome in response to metformin treatment by using a high-fat diet-induced type 2 diabetes mouse model of both sexes. Four intestinal parts, each at the luminal and mucosal layer level, were analyzed in this study by performing 16S rRNA sequencing covering six variable regions (V1-V6) of the gene and thus allowing to obtain in-depth information about the microbiome composition. We identified significant differences in gut microbiome diversity in each of the intestinal parts regarding the alpha and beta diversities. Metformin treatment altered the abundance of different genera in all studied intestinal sites, with the most pronounced effect in the small intestine, where Lactococcus increased remarkably. The abundance of Lactobacillus was substantially lower in male mice compared to female mice in all locations, in addition to an enrichment of opportunistic pathogens. Diet type and intestinal layer had significant effects on microbiome composition at each of the sites studied. We observed a different effect of metformin treatment on the analyzed subsets, indicating the multiple dimensions of metformin’s effect on the gut microbiome.https://www.tandfonline.com/doi/10.1080/19490976.2023.2188663Metformingut microbiomeintestinal partslumen and mucosaC57BL/6Nhigh-fat diet
spellingShingle Laila Silamiķele
Rihards Saksis
Ivars Silamiķelis
Patrīcija Paulīne Kotoviča
Monta Brīvība
Ineta Kalniņa
Zane Kalniņa
Dāvids Fridmanis
Jānis Kloviņš
Spatial variation of the gut microbiome in response to long-term metformin treatment in high-fat diet-induced type 2 diabetes mouse model of both sexes
Gut Microbes
Metformin
gut microbiome
intestinal parts
lumen and mucosa
C57BL/6N
high-fat diet
title Spatial variation of the gut microbiome in response to long-term metformin treatment in high-fat diet-induced type 2 diabetes mouse model of both sexes
title_full Spatial variation of the gut microbiome in response to long-term metformin treatment in high-fat diet-induced type 2 diabetes mouse model of both sexes
title_fullStr Spatial variation of the gut microbiome in response to long-term metformin treatment in high-fat diet-induced type 2 diabetes mouse model of both sexes
title_full_unstemmed Spatial variation of the gut microbiome in response to long-term metformin treatment in high-fat diet-induced type 2 diabetes mouse model of both sexes
title_short Spatial variation of the gut microbiome in response to long-term metformin treatment in high-fat diet-induced type 2 diabetes mouse model of both sexes
title_sort spatial variation of the gut microbiome in response to long term metformin treatment in high fat diet induced type 2 diabetes mouse model of both sexes
topic Metformin
gut microbiome
intestinal parts
lumen and mucosa
C57BL/6N
high-fat diet
url https://www.tandfonline.com/doi/10.1080/19490976.2023.2188663
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