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Disturbance of lipid metabolism in germ-free mice transplanted with gut microbiota of DSS-induced colitis mice

Hepatobiliary abnormality and metabolic disorders are frequently observed complications in patients with inflammatory bowel diseases (IBD). Given that microbiota dysbiosis is a common pathophysiological feature of both IBD and metabolic diseases, we examined how the IBD-induced dysbiosis affects the...

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Autores principales: Lee, Chungho, Kim, SangAh, Kim, Bobae, Holzapfel, Wilhelm H., Hyun, Chang-Kee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9897547/
https://www.ncbi.nlm.nih.gov/pubmed/36735734
http://dx.doi.org/10.1371/journal.pone.0280850
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author Lee, Chungho
Kim, SangAh
Kim, Bobae
Holzapfel, Wilhelm H.
Hyun, Chang-Kee
author_facet Lee, Chungho
Kim, SangAh
Kim, Bobae
Holzapfel, Wilhelm H.
Hyun, Chang-Kee
author_sort Lee, Chungho
collection PubMed
description Hepatobiliary abnormality and metabolic disorders are frequently observed complications in patients with inflammatory bowel diseases (IBD). Given that microbiota dysbiosis is a common pathophysiological feature of both IBD and metabolic diseases, we examined how the IBD-induced dysbiosis affects the host metabolism and contributes to the development of associated metabolic diseases using germ-free (GF) mice transplanted with fecal microbiota of DSS-induced colitis mice. There was no significant change in inflammation or barrier integrity in the gut of GF mice that received microbiota from colitis mice compared to their counterparts that were transplanted with microbiota from non-colitis healthy mice. Interestingly, it was observed that the GF recipients of colitis-induced altered microbiota showed a significant decrease in the weight of adipose tissues including mesenteric, epididymal, subcutaneous, and brown fat without any change in body weight, which was accompanied by abnormalities in adipose tissue functions such as fat storage and adiponectin production. Transplantation of colitis-induced altered microbiota also disrupted hepatic lipid metabolism in the GF recipient mice, which was observed by increases in synthesis and accumulation of cholesterol and bile acids in hepatocytes and a decrease in plasma HDL-cholesterol. Additional observations including elevated plasma levels of insulin, decreased hepatic production of FGF21, and decreased levels of fecal short chain fatty acids (SCFAs) and hepatic expression of SCFA receptors led to a conclusion that the transplantation of the colitis-associated dysbiotic microbiota was causally associated with impairments of insulin action and FGF21-adiponectin axis, possibly due to the low SCFA-producing capacity of the colonized microbiota, leading to metabolic abnormalities including adipose tissue dysfunction and dysregulated hepatic lipid metabolism. Our findings suggest potential mechanisms that explain how colitis-associated gut dysbiosis may contribute to the development of metabolic dysfunctions, which could be applied to clinical practice to improve the efficacy of treatment of IBD patients with comorbid metabolic disorders or vice versa.
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spelling pubmed-98975472023-02-04 Disturbance of lipid metabolism in germ-free mice transplanted with gut microbiota of DSS-induced colitis mice Lee, Chungho Kim, SangAh Kim, Bobae Holzapfel, Wilhelm H. Hyun, Chang-Kee PLoS One Research Article Hepatobiliary abnormality and metabolic disorders are frequently observed complications in patients with inflammatory bowel diseases (IBD). Given that microbiota dysbiosis is a common pathophysiological feature of both IBD and metabolic diseases, we examined how the IBD-induced dysbiosis affects the host metabolism and contributes to the development of associated metabolic diseases using germ-free (GF) mice transplanted with fecal microbiota of DSS-induced colitis mice. There was no significant change in inflammation or barrier integrity in the gut of GF mice that received microbiota from colitis mice compared to their counterparts that were transplanted with microbiota from non-colitis healthy mice. Interestingly, it was observed that the GF recipients of colitis-induced altered microbiota showed a significant decrease in the weight of adipose tissues including mesenteric, epididymal, subcutaneous, and brown fat without any change in body weight, which was accompanied by abnormalities in adipose tissue functions such as fat storage and adiponectin production. Transplantation of colitis-induced altered microbiota also disrupted hepatic lipid metabolism in the GF recipient mice, which was observed by increases in synthesis and accumulation of cholesterol and bile acids in hepatocytes and a decrease in plasma HDL-cholesterol. Additional observations including elevated plasma levels of insulin, decreased hepatic production of FGF21, and decreased levels of fecal short chain fatty acids (SCFAs) and hepatic expression of SCFA receptors led to a conclusion that the transplantation of the colitis-associated dysbiotic microbiota was causally associated with impairments of insulin action and FGF21-adiponectin axis, possibly due to the low SCFA-producing capacity of the colonized microbiota, leading to metabolic abnormalities including adipose tissue dysfunction and dysregulated hepatic lipid metabolism. Our findings suggest potential mechanisms that explain how colitis-associated gut dysbiosis may contribute to the development of metabolic dysfunctions, which could be applied to clinical practice to improve the efficacy of treatment of IBD patients with comorbid metabolic disorders or vice versa. Public Library of Science 2023-02-03 /pmc/articles/PMC9897547/ /pubmed/36735734 http://dx.doi.org/10.1371/journal.pone.0280850 Text en © 2023 Lee et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Lee, Chungho
Kim, SangAh
Kim, Bobae
Holzapfel, Wilhelm H.
Hyun, Chang-Kee
Disturbance of lipid metabolism in germ-free mice transplanted with gut microbiota of DSS-induced colitis mice
title Disturbance of lipid metabolism in germ-free mice transplanted with gut microbiota of DSS-induced colitis mice
title_full Disturbance of lipid metabolism in germ-free mice transplanted with gut microbiota of DSS-induced colitis mice
title_fullStr Disturbance of lipid metabolism in germ-free mice transplanted with gut microbiota of DSS-induced colitis mice
title_full_unstemmed Disturbance of lipid metabolism in germ-free mice transplanted with gut microbiota of DSS-induced colitis mice
title_short Disturbance of lipid metabolism in germ-free mice transplanted with gut microbiota of DSS-induced colitis mice
title_sort disturbance of lipid metabolism in germ-free mice transplanted with gut microbiota of dss-induced colitis mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9897547/
https://www.ncbi.nlm.nih.gov/pubmed/36735734
http://dx.doi.org/10.1371/journal.pone.0280850
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