The Kynurenine Pathway Is Upregulated by Methyl‐deficient Diet and Changes Are Averted by Probiotics

Scope Probiotics exert immunomodulatory effects and may influence tryptophan metabolism in the host. Deficiency of nutrients related to C1 metabolism might stimulate inflammation by enhancing the kynurenine pathway. This study used Sprague Dawley rats to investigate whether a methyl‐deficient diet (...

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Veröffentlicht in:Molecular nutrition & food research 2021-05, Vol.65 (9), p.e2100078-n/a
Hauptverfasser: Tillmann, Sandra, Awwad, Hussain M., MacPherson, Chad W., Happ, Denise F., Treccani, Giulia, Geisel, Juergen, Tompkins, Thomas A., Ueland, Per Magne, Wegener, Gregers, Obeid, Rima
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container_issue 9
container_start_page e2100078
container_title Molecular nutrition & food research
container_volume 65
creator Tillmann, Sandra
Awwad, Hussain M.
MacPherson, Chad W.
Happ, Denise F.
Treccani, Giulia
Geisel, Juergen
Tompkins, Thomas A.
Ueland, Per Magne
Wegener, Gregers
Obeid, Rima
description Scope Probiotics exert immunomodulatory effects and may influence tryptophan metabolism in the host. Deficiency of nutrients related to C1 metabolism might stimulate inflammation by enhancing the kynurenine pathway. This study used Sprague Dawley rats to investigate whether a methyl‐deficient diet (MDD) may influence tryptophan/kynurenine pathways and cytokines and whether probiotics can mitigate these effects. Methods and Results Rats are fed a control or MDD diet. Animals on the MDD diet received vehicle, probiotics (L. helveticus R0052 and B. longum R0175), choline, or probiotics + choline for 10 weeks (n = 10 per group). Concentrations of plasma kynurenine metabolites and the methylation and inflammatory markers in plasma and liver are measured. Results MDD animals (vs controls) show upregulation of plasma kynurenine, kynurenic acid, xanthurenic acid, 3‐hydroxyxanthranilic acid, quinolinic acid, nicotinic acid, and nicotinamide (all p
doi_str_mv 10.1002/mnfr.202100078
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Deficiency of nutrients related to C1 metabolism might stimulate inflammation by enhancing the kynurenine pathway. This study used Sprague Dawley rats to investigate whether a methyl‐deficient diet (MDD) may influence tryptophan/kynurenine pathways and cytokines and whether probiotics can mitigate these effects. Methods and Results Rats are fed a control or MDD diet. Animals on the MDD diet received vehicle, probiotics (L. helveticus R0052 and B. longum R0175), choline, or probiotics + choline for 10 weeks (n = 10 per group). Concentrations of plasma kynurenine metabolites and the methylation and inflammatory markers in plasma and liver are measured. Results MDD animals (vs controls) show upregulation of plasma kynurenine, kynurenic acid, xanthurenic acid, 3‐hydroxyxanthranilic acid, quinolinic acid, nicotinic acid, and nicotinamide (all p &lt; 0.05). In the MDD rats, the probiotics (vs vehicle) cause lower anthranilic acid and a trend towards lower kynurenic acid and picolinic acid. Compared to probiotics alone, probiotics + choline is associated with a reduced enrichment of the bacterial strains in cecum. The interventions have no effect on inflammatory markers. Conclusions Probiotics counterbalance the effect of MDD diet and downregulate downstream metabolites of the kynurenine pathway. A methyl‐deficient diet (MDD) causes higher serotonin and upregulation of the kynurenine pathway and is associated with weight reduction in the young animals. Intervention with probiotics (L. helveticus and B. longum) lowers plasma kynurenine metabolites. Intervention with choline causes slight downregulation of the kynurenine upstream metabolites. Probiotics counterbalance the effect of MDD and specifically downregulate downstream metabolites of the kynurenine pathway.</description><identifier>ISSN: 1613-4125</identifier><identifier>EISSN: 1613-4133</identifier><identifier>DOI: 10.1002/mnfr.202100078</identifier><identifier>PMID: 33686786</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>Acids ; Animals ; Anthranilic acid ; Cecum ; Choline ; Cytokines ; Diet ; Downstream effects ; Immunomodulation ; Inflammation ; Kynurenic acid ; kynurenine ; Markers ; Metabolism ; Metabolites ; Methylation ; methyl‐deficient diet ; Nicotinamide ; Nicotinic acid ; Nutrient deficiency ; Nutrients ; Picolinic acid ; Probiotics ; Quinolinic acid ; Tryptophan ; Xanthurenic acid</subject><ispartof>Molecular nutrition &amp; food research, 2021-05, Vol.65 (9), p.e2100078-n/a</ispartof><rights>2021 The Authors. 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Deficiency of nutrients related to C1 metabolism might stimulate inflammation by enhancing the kynurenine pathway. This study used Sprague Dawley rats to investigate whether a methyl‐deficient diet (MDD) may influence tryptophan/kynurenine pathways and cytokines and whether probiotics can mitigate these effects. Methods and Results Rats are fed a control or MDD diet. Animals on the MDD diet received vehicle, probiotics (L. helveticus R0052 and B. longum R0175), choline, or probiotics + choline for 10 weeks (n = 10 per group). Concentrations of plasma kynurenine metabolites and the methylation and inflammatory markers in plasma and liver are measured. Results MDD animals (vs controls) show upregulation of plasma kynurenine, kynurenic acid, xanthurenic acid, 3‐hydroxyxanthranilic acid, quinolinic acid, nicotinic acid, and nicotinamide (all p &lt; 0.05). In the MDD rats, the probiotics (vs vehicle) cause lower anthranilic acid and a trend towards lower kynurenic acid and picolinic acid. Compared to probiotics alone, probiotics + choline is associated with a reduced enrichment of the bacterial strains in cecum. The interventions have no effect on inflammatory markers. Conclusions Probiotics counterbalance the effect of MDD diet and downregulate downstream metabolites of the kynurenine pathway. A methyl‐deficient diet (MDD) causes higher serotonin and upregulation of the kynurenine pathway and is associated with weight reduction in the young animals. Intervention with probiotics (L. helveticus and B. longum) lowers plasma kynurenine metabolites. Intervention with choline causes slight downregulation of the kynurenine upstream metabolites. 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Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular nutrition &amp; food research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tillmann, Sandra</au><au>Awwad, Hussain M.</au><au>MacPherson, Chad W.</au><au>Happ, Denise F.</au><au>Treccani, Giulia</au><au>Geisel, Juergen</au><au>Tompkins, Thomas A.</au><au>Ueland, Per Magne</au><au>Wegener, Gregers</au><au>Obeid, Rima</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Kynurenine Pathway Is Upregulated by Methyl‐deficient Diet and Changes Are Averted by Probiotics</atitle><jtitle>Molecular nutrition &amp; food research</jtitle><addtitle>Mol Nutr Food Res</addtitle><date>2021-05</date><risdate>2021</risdate><volume>65</volume><issue>9</issue><spage>e2100078</spage><epage>n/a</epage><pages>e2100078-n/a</pages><issn>1613-4125</issn><eissn>1613-4133</eissn><abstract>Scope Probiotics exert immunomodulatory effects and may influence tryptophan metabolism in the host. Deficiency of nutrients related to C1 metabolism might stimulate inflammation by enhancing the kynurenine pathway. This study used Sprague Dawley rats to investigate whether a methyl‐deficient diet (MDD) may influence tryptophan/kynurenine pathways and cytokines and whether probiotics can mitigate these effects. Methods and Results Rats are fed a control or MDD diet. Animals on the MDD diet received vehicle, probiotics (L. helveticus R0052 and B. longum R0175), choline, or probiotics + choline for 10 weeks (n = 10 per group). Concentrations of plasma kynurenine metabolites and the methylation and inflammatory markers in plasma and liver are measured. Results MDD animals (vs controls) show upregulation of plasma kynurenine, kynurenic acid, xanthurenic acid, 3‐hydroxyxanthranilic acid, quinolinic acid, nicotinic acid, and nicotinamide (all p &lt; 0.05). In the MDD rats, the probiotics (vs vehicle) cause lower anthranilic acid and a trend towards lower kynurenic acid and picolinic acid. Compared to probiotics alone, probiotics + choline is associated with a reduced enrichment of the bacterial strains in cecum. The interventions have no effect on inflammatory markers. Conclusions Probiotics counterbalance the effect of MDD diet and downregulate downstream metabolites of the kynurenine pathway. A methyl‐deficient diet (MDD) causes higher serotonin and upregulation of the kynurenine pathway and is associated with weight reduction in the young animals. Intervention with probiotics (L. helveticus and B. longum) lowers plasma kynurenine metabolites. Intervention with choline causes slight downregulation of the kynurenine upstream metabolites. Probiotics counterbalance the effect of MDD and specifically downregulate downstream metabolites of the kynurenine pathway.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>33686786</pmid><doi>10.1002/mnfr.202100078</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-0064-7029</orcidid><oa>free_for_read</oa></addata></record>
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subjects Acids
Animals
Anthranilic acid
Cecum
Choline
Cytokines
Diet
Downstream effects
Immunomodulation
Inflammation
Kynurenic acid
kynurenine
Markers
Metabolism
Metabolites
Methylation
methyl‐deficient diet
Nicotinamide
Nicotinic acid
Nutrient deficiency
Nutrients
Picolinic acid
Probiotics
Quinolinic acid
Tryptophan
Xanthurenic acid
title The Kynurenine Pathway Is Upregulated by Methyl‐deficient Diet and Changes Are Averted by Probiotics
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