Cargando…
Fish Oil Attenuates Omega-6 Polyunsaturated Fatty Acid-Induced Dysbiosis and Infectious Colitis but Impairs LPS Dephosphorylation Activity Causing Sepsis
Clinically, excessive ω-6 polyunsaturated fatty acid (PUFA) and inadequate ω-3 PUFA have been associated with enhanced risks for developing ulcerative colitis. In rodent models, ω-3 PUFAs have been shown to either attenuate or exacerbate colitis in different studies. We hypothesized that a high ω-6:...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3566198/ https://www.ncbi.nlm.nih.gov/pubmed/23405155 http://dx.doi.org/10.1371/journal.pone.0055468 |
_version_ | 1782258553013141504 |
---|---|
author | Ghosh, Sanjoy DeCoffe, Daniella Brown, Kirsty Rajendiran, Ethendhar Estaki, Mehrbod Dai, Chuanbin Yip, Ashley Gibson, Deanna L. |
author_facet | Ghosh, Sanjoy DeCoffe, Daniella Brown, Kirsty Rajendiran, Ethendhar Estaki, Mehrbod Dai, Chuanbin Yip, Ashley Gibson, Deanna L. |
author_sort | Ghosh, Sanjoy |
collection | PubMed |
description | Clinically, excessive ω-6 polyunsaturated fatty acid (PUFA) and inadequate ω-3 PUFA have been associated with enhanced risks for developing ulcerative colitis. In rodent models, ω-3 PUFAs have been shown to either attenuate or exacerbate colitis in different studies. We hypothesized that a high ω-6: ω-3 PUFA ratio would increase colitis susceptibility through the microbe-immunity nexus. To address this, we fed post-weaned mice diets rich in ω-6 PUFA (corn oil) and diets supplemented with ω-3 PUFA (corn oil+fish oil) for 5 weeks. We evaluated the intestinal microbiota, induced colitis with Citrobacter rodentium and followed disease progression. We found that ω-6 PUFA enriched the microbiota with Enterobacteriaceae, Segmented Filamentous Bacteria and Clostridia spp., all known to induce inflammation. During infection-induced colitis, ω-6 PUFA fed mice had exacerbated intestinal damage, immune cell infiltration, prostaglandin E2 expression and C. rodentium translocation across the intestinal mucosae. Addition of ω-3 PUFA on a high ω-6 PUFA diet, reversed inflammatory-inducing microbial blooms and enriched beneficial microbes like Lactobacillus and Bifidobacteria, reduced immune cell infiltration and impaired cytokine/chemokine induction during infection. While, ω-3 PUFA supplementation protected against severe colitis, these mice suffered greater mortality associated with sepsis-related serum factors such as LPS binding protein, IL-15 and TNF-α. These mice also demonstrated decreased expression of intestinal alkaline phosphatase and an inability to dephosphorylate LPS. Thus, the colonic microbiota is altered differentially through varying PUFA composition, conferring altered susceptibility to colitis. Overall, ω-6 PUFA enriches pro-inflammatory microbes and augments colitis; but prevents infection-induced systemic inflammation. In contrast, ω-3 PUFA supplementation reverses the effects of the ω-6 PUFA diet but impairs infection-induced responses resulting in sepsis. We conclude that as an anti-inflammatory agent, ω-3 PUFA supplementation during infection may prove detrimental when host inflammatory responses are critical for survival. |
format | Online Article Text |
id | pubmed-3566198 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35661982013-02-12 Fish Oil Attenuates Omega-6 Polyunsaturated Fatty Acid-Induced Dysbiosis and Infectious Colitis but Impairs LPS Dephosphorylation Activity Causing Sepsis Ghosh, Sanjoy DeCoffe, Daniella Brown, Kirsty Rajendiran, Ethendhar Estaki, Mehrbod Dai, Chuanbin Yip, Ashley Gibson, Deanna L. PLoS One Research Article Clinically, excessive ω-6 polyunsaturated fatty acid (PUFA) and inadequate ω-3 PUFA have been associated with enhanced risks for developing ulcerative colitis. In rodent models, ω-3 PUFAs have been shown to either attenuate or exacerbate colitis in different studies. We hypothesized that a high ω-6: ω-3 PUFA ratio would increase colitis susceptibility through the microbe-immunity nexus. To address this, we fed post-weaned mice diets rich in ω-6 PUFA (corn oil) and diets supplemented with ω-3 PUFA (corn oil+fish oil) for 5 weeks. We evaluated the intestinal microbiota, induced colitis with Citrobacter rodentium and followed disease progression. We found that ω-6 PUFA enriched the microbiota with Enterobacteriaceae, Segmented Filamentous Bacteria and Clostridia spp., all known to induce inflammation. During infection-induced colitis, ω-6 PUFA fed mice had exacerbated intestinal damage, immune cell infiltration, prostaglandin E2 expression and C. rodentium translocation across the intestinal mucosae. Addition of ω-3 PUFA on a high ω-6 PUFA diet, reversed inflammatory-inducing microbial blooms and enriched beneficial microbes like Lactobacillus and Bifidobacteria, reduced immune cell infiltration and impaired cytokine/chemokine induction during infection. While, ω-3 PUFA supplementation protected against severe colitis, these mice suffered greater mortality associated with sepsis-related serum factors such as LPS binding protein, IL-15 and TNF-α. These mice also demonstrated decreased expression of intestinal alkaline phosphatase and an inability to dephosphorylate LPS. Thus, the colonic microbiota is altered differentially through varying PUFA composition, conferring altered susceptibility to colitis. Overall, ω-6 PUFA enriches pro-inflammatory microbes and augments colitis; but prevents infection-induced systemic inflammation. In contrast, ω-3 PUFA supplementation reverses the effects of the ω-6 PUFA diet but impairs infection-induced responses resulting in sepsis. We conclude that as an anti-inflammatory agent, ω-3 PUFA supplementation during infection may prove detrimental when host inflammatory responses are critical for survival. Public Library of Science 2013-02-06 /pmc/articles/PMC3566198/ /pubmed/23405155 http://dx.doi.org/10.1371/journal.pone.0055468 Text en © 2013 Ghosh et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Ghosh, Sanjoy DeCoffe, Daniella Brown, Kirsty Rajendiran, Ethendhar Estaki, Mehrbod Dai, Chuanbin Yip, Ashley Gibson, Deanna L. Fish Oil Attenuates Omega-6 Polyunsaturated Fatty Acid-Induced Dysbiosis and Infectious Colitis but Impairs LPS Dephosphorylation Activity Causing Sepsis |
title | Fish Oil Attenuates Omega-6 Polyunsaturated Fatty Acid-Induced Dysbiosis and Infectious Colitis but Impairs LPS Dephosphorylation Activity Causing Sepsis |
title_full | Fish Oil Attenuates Omega-6 Polyunsaturated Fatty Acid-Induced Dysbiosis and Infectious Colitis but Impairs LPS Dephosphorylation Activity Causing Sepsis |
title_fullStr | Fish Oil Attenuates Omega-6 Polyunsaturated Fatty Acid-Induced Dysbiosis and Infectious Colitis but Impairs LPS Dephosphorylation Activity Causing Sepsis |
title_full_unstemmed | Fish Oil Attenuates Omega-6 Polyunsaturated Fatty Acid-Induced Dysbiosis and Infectious Colitis but Impairs LPS Dephosphorylation Activity Causing Sepsis |
title_short | Fish Oil Attenuates Omega-6 Polyunsaturated Fatty Acid-Induced Dysbiosis and Infectious Colitis but Impairs LPS Dephosphorylation Activity Causing Sepsis |
title_sort | fish oil attenuates omega-6 polyunsaturated fatty acid-induced dysbiosis and infectious colitis but impairs lps dephosphorylation activity causing sepsis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3566198/ https://www.ncbi.nlm.nih.gov/pubmed/23405155 http://dx.doi.org/10.1371/journal.pone.0055468 |
work_keys_str_mv | AT ghoshsanjoy fishoilattenuatesomega6polyunsaturatedfattyacidinduceddysbiosisandinfectiouscolitisbutimpairslpsdephosphorylationactivitycausingsepsis AT decoffedaniella fishoilattenuatesomega6polyunsaturatedfattyacidinduceddysbiosisandinfectiouscolitisbutimpairslpsdephosphorylationactivitycausingsepsis AT brownkirsty fishoilattenuatesomega6polyunsaturatedfattyacidinduceddysbiosisandinfectiouscolitisbutimpairslpsdephosphorylationactivitycausingsepsis AT rajendiranethendhar fishoilattenuatesomega6polyunsaturatedfattyacidinduceddysbiosisandinfectiouscolitisbutimpairslpsdephosphorylationactivitycausingsepsis AT estakimehrbod fishoilattenuatesomega6polyunsaturatedfattyacidinduceddysbiosisandinfectiouscolitisbutimpairslpsdephosphorylationactivitycausingsepsis AT daichuanbin fishoilattenuatesomega6polyunsaturatedfattyacidinduceddysbiosisandinfectiouscolitisbutimpairslpsdephosphorylationactivitycausingsepsis AT yipashley fishoilattenuatesomega6polyunsaturatedfattyacidinduceddysbiosisandinfectiouscolitisbutimpairslpsdephosphorylationactivitycausingsepsis AT gibsondeannal fishoilattenuatesomega6polyunsaturatedfattyacidinduceddysbiosisandinfectiouscolitisbutimpairslpsdephosphorylationactivitycausingsepsis |