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Indole-3-lactic acid associated with Bifidobacterium-dominated microbiota significantly decreases inflammation in intestinal epithelial cells

BACKGROUND: Bifidobacterium longum subsp. infantis (B. infantis) is a commensal bacterium that colonizes the gastrointestinal tract of breast-fed infants. B. infantis can efficiently utilize the abundant supply of oligosaccharides found in human milk (HMO) to help establish residence. We hypothesize...

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Autores principales: Ehrlich, Amy M., Pacheco, Alline R., Henrick, Bethany M., Taft, Diana, Xu, Gege, Huda, M. Nazmul, Mishchuk, Darya, Goodson, Michael L., Slupsky, Carolyn, Barile, Daniela, Lebrilla, Carlito B., Stephensen, Charles B., Mills, David A., Raybould, Helen E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7681996/
https://www.ncbi.nlm.nih.gov/pubmed/33225894
http://dx.doi.org/10.1186/s12866-020-02023-y
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author Ehrlich, Amy M.
Pacheco, Alline R.
Henrick, Bethany M.
Taft, Diana
Xu, Gege
Huda, M. Nazmul
Mishchuk, Darya
Goodson, Michael L.
Slupsky, Carolyn
Barile, Daniela
Lebrilla, Carlito B.
Stephensen, Charles B.
Mills, David A.
Raybould, Helen E.
author_facet Ehrlich, Amy M.
Pacheco, Alline R.
Henrick, Bethany M.
Taft, Diana
Xu, Gege
Huda, M. Nazmul
Mishchuk, Darya
Goodson, Michael L.
Slupsky, Carolyn
Barile, Daniela
Lebrilla, Carlito B.
Stephensen, Charles B.
Mills, David A.
Raybould, Helen E.
author_sort Ehrlich, Amy M.
collection PubMed
description BACKGROUND: Bifidobacterium longum subsp. infantis (B. infantis) is a commensal bacterium that colonizes the gastrointestinal tract of breast-fed infants. B. infantis can efficiently utilize the abundant supply of oligosaccharides found in human milk (HMO) to help establish residence. We hypothesized that metabolites from B. infantis grown on HMO produce a beneficial effect on the host. RESULTS: In a previous study, we demonstrated that B. infantis routinely dominated the fecal microbiota of a breast fed Bangladeshi infant cohort (1). Characterization of the fecal metabolome of binned samples representing high and low B. infantis populations from this cohort revealed higher amounts of the tryptophan metabolite indole-3-lactic acid (ILA) in feces with high levels of B. infantis. Further in vitro analysis confirmed that B. infantis produced significantly greater quantities of the ILA when grown on HMO versus lactose, suggesting a growth substrate relationship to ILA production. The direct effects of ILA were assessed in a macrophage cell line and intestinal epithelial cell lines. ILA (1-10 mM) significantly attenuated lipopolysaccharide (LPS)-induced activation of NF-kB in macrophages. ILA significantly attenuated TNF-α- and LPS-induced increase in the pro-inflammatory cytokine IL-8 in intestinal epithelial cells. ILA increased mRNA expression of the aryl hydrogen receptor (AhR)-target gene CYP1A1 and nuclear factor erythroid 2–related factor 2 (Nrf2)-targeted genes glutathione reductase 2 (GPX2), superoxide dismutase 2 (SOD2), and NAD(P) H dehydrogenase (NQO1). Pretreatment with either the AhR antagonist or Nrf-2 antagonist inhibited the response of ILA on downstream effectors. CONCLUSIONS: These findings suggest that ILA, a predominant metabolite from B. infantis grown on HMO and elevated in infant stool high in B. infantis, and protects gut epithelial cells in culture via activation of the AhR and Nrf2 pathway. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12866-020-02023-y.
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spelling pubmed-76819962020-11-23 Indole-3-lactic acid associated with Bifidobacterium-dominated microbiota significantly decreases inflammation in intestinal epithelial cells Ehrlich, Amy M. Pacheco, Alline R. Henrick, Bethany M. Taft, Diana Xu, Gege Huda, M. Nazmul Mishchuk, Darya Goodson, Michael L. Slupsky, Carolyn Barile, Daniela Lebrilla, Carlito B. Stephensen, Charles B. Mills, David A. Raybould, Helen E. BMC Microbiol Research Article BACKGROUND: Bifidobacterium longum subsp. infantis (B. infantis) is a commensal bacterium that colonizes the gastrointestinal tract of breast-fed infants. B. infantis can efficiently utilize the abundant supply of oligosaccharides found in human milk (HMO) to help establish residence. We hypothesized that metabolites from B. infantis grown on HMO produce a beneficial effect on the host. RESULTS: In a previous study, we demonstrated that B. infantis routinely dominated the fecal microbiota of a breast fed Bangladeshi infant cohort (1). Characterization of the fecal metabolome of binned samples representing high and low B. infantis populations from this cohort revealed higher amounts of the tryptophan metabolite indole-3-lactic acid (ILA) in feces with high levels of B. infantis. Further in vitro analysis confirmed that B. infantis produced significantly greater quantities of the ILA when grown on HMO versus lactose, suggesting a growth substrate relationship to ILA production. The direct effects of ILA were assessed in a macrophage cell line and intestinal epithelial cell lines. ILA (1-10 mM) significantly attenuated lipopolysaccharide (LPS)-induced activation of NF-kB in macrophages. ILA significantly attenuated TNF-α- and LPS-induced increase in the pro-inflammatory cytokine IL-8 in intestinal epithelial cells. ILA increased mRNA expression of the aryl hydrogen receptor (AhR)-target gene CYP1A1 and nuclear factor erythroid 2–related factor 2 (Nrf2)-targeted genes glutathione reductase 2 (GPX2), superoxide dismutase 2 (SOD2), and NAD(P) H dehydrogenase (NQO1). Pretreatment with either the AhR antagonist or Nrf-2 antagonist inhibited the response of ILA on downstream effectors. CONCLUSIONS: These findings suggest that ILA, a predominant metabolite from B. infantis grown on HMO and elevated in infant stool high in B. infantis, and protects gut epithelial cells in culture via activation of the AhR and Nrf2 pathway. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12866-020-02023-y. BioMed Central 2020-11-23 /pmc/articles/PMC7681996/ /pubmed/33225894 http://dx.doi.org/10.1186/s12866-020-02023-y Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Ehrlich, Amy M.
Pacheco, Alline R.
Henrick, Bethany M.
Taft, Diana
Xu, Gege
Huda, M. Nazmul
Mishchuk, Darya
Goodson, Michael L.
Slupsky, Carolyn
Barile, Daniela
Lebrilla, Carlito B.
Stephensen, Charles B.
Mills, David A.
Raybould, Helen E.
Indole-3-lactic acid associated with Bifidobacterium-dominated microbiota significantly decreases inflammation in intestinal epithelial cells
title Indole-3-lactic acid associated with Bifidobacterium-dominated microbiota significantly decreases inflammation in intestinal epithelial cells
title_full Indole-3-lactic acid associated with Bifidobacterium-dominated microbiota significantly decreases inflammation in intestinal epithelial cells
title_fullStr Indole-3-lactic acid associated with Bifidobacterium-dominated microbiota significantly decreases inflammation in intestinal epithelial cells
title_full_unstemmed Indole-3-lactic acid associated with Bifidobacterium-dominated microbiota significantly decreases inflammation in intestinal epithelial cells
title_short Indole-3-lactic acid associated with Bifidobacterium-dominated microbiota significantly decreases inflammation in intestinal epithelial cells
title_sort indole-3-lactic acid associated with bifidobacterium-dominated microbiota significantly decreases inflammation in intestinal epithelial cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7681996/
https://www.ncbi.nlm.nih.gov/pubmed/33225894
http://dx.doi.org/10.1186/s12866-020-02023-y
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