Dietary Isoflavones Alter Gut Microbiota and Lipopolysaccharide Biosynthesis to Reduce Inflammation

The etiopathogenesis of multiple sclerosis (MS) is strongly affected by environmental factors such as diet and the gut microbiota. An isoflavone-rich (ISO) diet was previously shown to reduce the severity of MS in the animal model experimental autoimmune encephalomyelitis (EAE). Translation of this...

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Main Authors: Sudeep Ghimire, Nicole M. Cady, Peter Lehman, Stephanie R. Peterson, Shailesh K. Shahi, Faraz Rashid, Shailendra Giri, Ashutosh K. Mangalam
Format: Article
Language:English
Published: Taylor & Francis Group 2022-12-01
Series:Gut Microbes
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Online Access:https://www.tandfonline.com/doi/10.1080/19490976.2022.2127446
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author Sudeep Ghimire
Nicole M. Cady
Peter Lehman
Stephanie R. Peterson
Shailesh K. Shahi
Faraz Rashid
Shailendra Giri
Ashutosh K. Mangalam
author_facet Sudeep Ghimire
Nicole M. Cady
Peter Lehman
Stephanie R. Peterson
Shailesh K. Shahi
Faraz Rashid
Shailendra Giri
Ashutosh K. Mangalam
author_sort Sudeep Ghimire
collection DOAJ
description The etiopathogenesis of multiple sclerosis (MS) is strongly affected by environmental factors such as diet and the gut microbiota. An isoflavone-rich (ISO) diet was previously shown to reduce the severity of MS in the animal model experimental autoimmune encephalomyelitis (EAE). Translation of this concept to clinical trial where dietary isoflavones may be recommended for MS patients will require preliminary evidence that providing the isoflavone-rich diet to people with MS (PwMS) who lack phytoestrogen-metabolizing bacteria has beneficial effects. We have previously shown that the gut microbiota of PwMS resembles the gut microbiota of mice raised under a phytoestrogen-free (phyto-free) diet in that it lacks phytoestrogen-metabolizing bacteria. To investigate the effects of phytoestrogens on the microbiota inflammatory response and EAE disease severity we switched the diet of mice raised under a phyto-free (PF) diet to an isoflavone-rich diet. Microbiota analysis showed that the change in diet from one that is ISO to one that is PF reduces beneficial bacteria such as Bifidobacterium species. In addition we observed functional differences in lipopolysaccharide (LPS) biosynthesis pathways. Moreover LPS extracted from feces of mice fed an ISO diet induced increased production of anti-inflammatory cytokines from bone marrow-derived macrophages relative to fecal-LPS isolated from mice fed a PF diet. Eventually mice whose diet was switched from a PF diet to an ISO diet trended toward reduced EAE severity and mortality. Overall we show that an isoflavone-rich diet specifically modulates LPS biosynthesis of the gut microbiota imparts an anti-inflammatory response and decreases disease severity.
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spelling doaj-art-45fb49804d1748bf843a799de5fa49542025-08-20T03:21:42ZengTaylor & Francis GroupGut Microbes1949-09761949-09842022-12-0114110.1080/19490976.2022.2127446Dietary Isoflavones Alter Gut Microbiota and Lipopolysaccharide Biosynthesis to Reduce InflammationSudeep Ghimire0Nicole M. Cady1Peter Lehman2Stephanie R. Peterson3Shailesh K. Shahi4Faraz Rashid5Shailendra Giri6Ashutosh K. Mangalam7Department of Pathology University of Iowa Iowa City Iowa USADepartment of Pathology University of Iowa Iowa City Iowa USADepartment of Pathology University of Iowa Iowa City Iowa USADepartment of Pathology University of Iowa Iowa City Iowa USADepartment of Pathology University of Iowa Iowa City Iowa USADepartment of Neurology Henry Ford Health System Detroit MI USADepartment of Neurology Henry Ford Health System Detroit MI USADepartment of Pathology University of Iowa Iowa City Iowa USAThe etiopathogenesis of multiple sclerosis (MS) is strongly affected by environmental factors such as diet and the gut microbiota. An isoflavone-rich (ISO) diet was previously shown to reduce the severity of MS in the animal model experimental autoimmune encephalomyelitis (EAE). Translation of this concept to clinical trial where dietary isoflavones may be recommended for MS patients will require preliminary evidence that providing the isoflavone-rich diet to people with MS (PwMS) who lack phytoestrogen-metabolizing bacteria has beneficial effects. We have previously shown that the gut microbiota of PwMS resembles the gut microbiota of mice raised under a phytoestrogen-free (phyto-free) diet in that it lacks phytoestrogen-metabolizing bacteria. To investigate the effects of phytoestrogens on the microbiota inflammatory response and EAE disease severity we switched the diet of mice raised under a phyto-free (PF) diet to an isoflavone-rich diet. Microbiota analysis showed that the change in diet from one that is ISO to one that is PF reduces beneficial bacteria such as Bifidobacterium species. In addition we observed functional differences in lipopolysaccharide (LPS) biosynthesis pathways. Moreover LPS extracted from feces of mice fed an ISO diet induced increased production of anti-inflammatory cytokines from bone marrow-derived macrophages relative to fecal-LPS isolated from mice fed a PF diet. Eventually mice whose diet was switched from a PF diet to an ISO diet trended toward reduced EAE severity and mortality. Overall we show that an isoflavone-rich diet specifically modulates LPS biosynthesis of the gut microbiota imparts an anti-inflammatory response and decreases disease severity.https://www.tandfonline.com/doi/10.1080/19490976.2022.2127446Gut microbiotaisoflavoneslipopolysaccharidesdietEAE
spellingShingle Sudeep Ghimire
Nicole M. Cady
Peter Lehman
Stephanie R. Peterson
Shailesh K. Shahi
Faraz Rashid
Shailendra Giri
Ashutosh K. Mangalam
Dietary Isoflavones Alter Gut Microbiota and Lipopolysaccharide Biosynthesis to Reduce Inflammation
Gut Microbes
Gut microbiota
isoflavones
lipopolysaccharides
diet
EAE
title Dietary Isoflavones Alter Gut Microbiota and Lipopolysaccharide Biosynthesis to Reduce Inflammation
title_full Dietary Isoflavones Alter Gut Microbiota and Lipopolysaccharide Biosynthesis to Reduce Inflammation
title_fullStr Dietary Isoflavones Alter Gut Microbiota and Lipopolysaccharide Biosynthesis to Reduce Inflammation
title_full_unstemmed Dietary Isoflavones Alter Gut Microbiota and Lipopolysaccharide Biosynthesis to Reduce Inflammation
title_short Dietary Isoflavones Alter Gut Microbiota and Lipopolysaccharide Biosynthesis to Reduce Inflammation
title_sort dietary isoflavones alter gut microbiota and lipopolysaccharide biosynthesis to reduce inflammation
topic Gut microbiota
isoflavones
lipopolysaccharides
diet
EAE
url https://www.tandfonline.com/doi/10.1080/19490976.2022.2127446
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