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Lactobacillus rhamnosus CNCMI-4317 Modulates Fiaf/Angptl4 in Intestinal Epithelial Cells and Circulating Level in Mice.

Jacouton E, Mach N, Cadiou J, Lapaque N, Clément K, Doré J, van Hylckama Vlieg JE, Smokvina T, Blottière HM - PLoS ONE (2015)

Bottom Line: Lactobacilli are often considered to display beneficial effect for their hosts, acting on different regulatory pathways.We then validated in vivo bacterial effects using C57BL/6 mono-colonized mice fed with normal chow.Moreover, this effect was accompanied by transcriptome modulation of several pathways including immune response and metabolism in vitro.

View Article: PubMed Central - PubMed

Affiliation: Danone Nutricia Research, Palaiseau, France; INRA, UMR 1319 Micalis, Jouy en Josas, France; AgroParistech, UMR Micalis, Jouy en Josas, France.

ABSTRACT

Background and objectives: Identification of new targets for metabolic diseases treatment or prevention is required. In this context, FIAF/ANGPTL4 appears as a crucial regulator of energy homeostasis. Lactobacilli are often considered to display beneficial effect for their hosts, acting on different regulatory pathways. The aim of the present work was to study the effect of several lactobacilli strains on Fiaf gene expression in human intestinal epithelial cells (IECs) and on mice tissues to decipher the underlying mechanisms.

Subjects and methods: Nineteen lactobacilli strains have been tested on HT-29 human intestinal epithelial cells for their ability to regulate Fiaf gene expression by RT-qPCR. In order to determine regulated pathways, we analysed the whole genome transcriptome of IECs. We then validated in vivo bacterial effects using C57BL/6 mono-colonized mice fed with normal chow.

Results: We identified one strain (Lactobacillus rhamnosus CNCMI-4317) that modulated Fiaf expression in IECs. This regulation relied potentially on bacterial surface-exposed molecules and seemed to be PPAR-γ independent but PPAR-α dependent. Transcriptome functional analysis revealed that multiple pathways including cellular function and maintenance, lymphoid tissue structure and development, as well as lipid metabolism were regulated by this strain. The regulation of immune system and lipid and carbohydrate metabolism was also confirmed by overrepresentation of Gene Ontology terms analysis. In vivo, circulating FIAF protein was increased by the strain but this phenomenon was not correlated with modulation Fiaf expression in tissues (except a trend in distal small intestine).

Conclusion: We showed that Lactobacillus rhamnosus CNCMI-4317 induced Fiaf expression in human IECs, and increased circulating FIAF protein level in mice. Moreover, this effect was accompanied by transcriptome modulation of several pathways including immune response and metabolism in vitro.

No MeSH data available.


Related in: MedlinePlus

Effect of L. rhamnosus and L. paracasei on Fiaf expression in IECs. Cells were stimulated 6h with 20% of final volume of bacterial cultures.Bars represent mean of Fiaf relative expression (percentage of rosiglitazone) from two to seven independent experiments performed in triplicates. Clear bars correspond to L. paracasei strains and dark bars correspond to L. rhamnosus strains. Data are normalized using β-Actin as control gene. Stars represent p<0.001 (***) in comparison with negative control (DMEM).
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pone.0138880.g001: Effect of L. rhamnosus and L. paracasei on Fiaf expression in IECs. Cells were stimulated 6h with 20% of final volume of bacterial cultures.Bars represent mean of Fiaf relative expression (percentage of rosiglitazone) from two to seven independent experiments performed in triplicates. Clear bars correspond to L. paracasei strains and dark bars correspond to L. rhamnosus strains. Data are normalized using β-Actin as control gene. Stars represent p<0.001 (***) in comparison with negative control (DMEM).

Mentions: In order to evaluate the potential of the two Lactobacillus species (L. rhamnosus, L. paracasei) in regulating host metabolism, we tested 19 bacterial strains for their ability to modulate Fiaf gene expression in IECs by RT-qPCR. HT–29 human epithelial cells were exposed to each bacteria at OD600nm = 0.1 for 6h before RNA extraction. Among the 10 L. paracasei and 9 L. rhamnosus strains tested (detailed in Table A in S1 File), L. rhamnosus CNCMI–4317 showed the most effective activation of Fiaf gene expression (P<0.001) (Fig 1) suggesting a strain specific effect. This activation corresponded to about 65% of the one induced by rosiglitazone, a selective PPAR-γ ligand (used as positive control). So, we decided to focus our mechanistic analysis on the bacterial strain using L. rhamnosus CNCMI–2493 as bacterial negative control and L. Rhamnosus CNCM–4317.


Lactobacillus rhamnosus CNCMI-4317 Modulates Fiaf/Angptl4 in Intestinal Epithelial Cells and Circulating Level in Mice.

Jacouton E, Mach N, Cadiou J, Lapaque N, Clément K, Doré J, van Hylckama Vlieg JE, Smokvina T, Blottière HM - PLoS ONE (2015)

Effect of L. rhamnosus and L. paracasei on Fiaf expression in IECs. Cells were stimulated 6h with 20% of final volume of bacterial cultures.Bars represent mean of Fiaf relative expression (percentage of rosiglitazone) from two to seven independent experiments performed in triplicates. Clear bars correspond to L. paracasei strains and dark bars correspond to L. rhamnosus strains. Data are normalized using β-Actin as control gene. Stars represent p<0.001 (***) in comparison with negative control (DMEM).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4595210&req=5

pone.0138880.g001: Effect of L. rhamnosus and L. paracasei on Fiaf expression in IECs. Cells were stimulated 6h with 20% of final volume of bacterial cultures.Bars represent mean of Fiaf relative expression (percentage of rosiglitazone) from two to seven independent experiments performed in triplicates. Clear bars correspond to L. paracasei strains and dark bars correspond to L. rhamnosus strains. Data are normalized using β-Actin as control gene. Stars represent p<0.001 (***) in comparison with negative control (DMEM).
Mentions: In order to evaluate the potential of the two Lactobacillus species (L. rhamnosus, L. paracasei) in regulating host metabolism, we tested 19 bacterial strains for their ability to modulate Fiaf gene expression in IECs by RT-qPCR. HT–29 human epithelial cells were exposed to each bacteria at OD600nm = 0.1 for 6h before RNA extraction. Among the 10 L. paracasei and 9 L. rhamnosus strains tested (detailed in Table A in S1 File), L. rhamnosus CNCMI–4317 showed the most effective activation of Fiaf gene expression (P<0.001) (Fig 1) suggesting a strain specific effect. This activation corresponded to about 65% of the one induced by rosiglitazone, a selective PPAR-γ ligand (used as positive control). So, we decided to focus our mechanistic analysis on the bacterial strain using L. rhamnosus CNCMI–2493 as bacterial negative control and L. Rhamnosus CNCM–4317.

Bottom Line: Lactobacilli are often considered to display beneficial effect for their hosts, acting on different regulatory pathways.We then validated in vivo bacterial effects using C57BL/6 mono-colonized mice fed with normal chow.Moreover, this effect was accompanied by transcriptome modulation of several pathways including immune response and metabolism in vitro.

View Article: PubMed Central - PubMed

Affiliation: Danone Nutricia Research, Palaiseau, France; INRA, UMR 1319 Micalis, Jouy en Josas, France; AgroParistech, UMR Micalis, Jouy en Josas, France.

ABSTRACT

Background and objectives: Identification of new targets for metabolic diseases treatment or prevention is required. In this context, FIAF/ANGPTL4 appears as a crucial regulator of energy homeostasis. Lactobacilli are often considered to display beneficial effect for their hosts, acting on different regulatory pathways. The aim of the present work was to study the effect of several lactobacilli strains on Fiaf gene expression in human intestinal epithelial cells (IECs) and on mice tissues to decipher the underlying mechanisms.

Subjects and methods: Nineteen lactobacilli strains have been tested on HT-29 human intestinal epithelial cells for their ability to regulate Fiaf gene expression by RT-qPCR. In order to determine regulated pathways, we analysed the whole genome transcriptome of IECs. We then validated in vivo bacterial effects using C57BL/6 mono-colonized mice fed with normal chow.

Results: We identified one strain (Lactobacillus rhamnosus CNCMI-4317) that modulated Fiaf expression in IECs. This regulation relied potentially on bacterial surface-exposed molecules and seemed to be PPAR-γ independent but PPAR-α dependent. Transcriptome functional analysis revealed that multiple pathways including cellular function and maintenance, lymphoid tissue structure and development, as well as lipid metabolism were regulated by this strain. The regulation of immune system and lipid and carbohydrate metabolism was also confirmed by overrepresentation of Gene Ontology terms analysis. In vivo, circulating FIAF protein was increased by the strain but this phenomenon was not correlated with modulation Fiaf expression in tissues (except a trend in distal small intestine).

Conclusion: We showed that Lactobacillus rhamnosus CNCMI-4317 induced Fiaf expression in human IECs, and increased circulating FIAF protein level in mice. Moreover, this effect was accompanied by transcriptome modulation of several pathways including immune response and metabolism in vitro.

No MeSH data available.


Related in: MedlinePlus