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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

In vivo, (a) FIAF circulating level, (b) Fiaf expression in the gut, and (c) IL7. (a-c) Circulating Fiaf and Il–7 was measured using Elisa tests. (b) Fiaf expression was determined via RT-qPCR.Stars indicate p<0.05 (*) in comparison with GF control group (PBS). DSI (distal small intestine), PSI (proximal small intestine), P = 0.14 (Student’s t-test) corresponds to L. rhamnosus CNCMI– 4317 versus control (PBS).
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pone.0138880.g006: In vivo, (a) FIAF circulating level, (b) Fiaf expression in the gut, and (c) IL7. (a-c) Circulating Fiaf and Il–7 was measured using Elisa tests. (b) Fiaf expression was determined via RT-qPCR.Stars indicate p<0.05 (*) in comparison with GF control group (PBS). DSI (distal small intestine), PSI (proximal small intestine), P = 0.14 (Student’s t-test) corresponds to L. rhamnosus CNCMI– 4317 versus control (PBS).

Mentions: Germ-free mice were colonized with L. rhamnosus CNCMI–4317 strain, L. rhamnosus CNCMI–2493 (control strain) or PBS during 11 days and then sacrificed. Mice colonized with L. rhamnosus CNCMI–4317 presented an increase in the concentration of plasma FIAF as compared to control mice (Fig 6a). With regard to the Fiaf gene expression among different tissues, the Fiaf gene expression tended to increase in the distal small intestine in the presence of L. rhamnosus CNCMI–4317 (P = 0.14), but no significant differences could be observed for colonic expression (Fig 6b). Furthermore, circulating FIAF level was not correlated to the expression of Fiaf gene expression in adipose tissues nor in the liver (S3a and S3b Fig).


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)

In vivo, (a) FIAF circulating level, (b) Fiaf expression in the gut, and (c) IL7. (a-c) Circulating Fiaf and Il–7 was measured using Elisa tests. (b) Fiaf expression was determined via RT-qPCR.Stars indicate p<0.05 (*) in comparison with GF control group (PBS). DSI (distal small intestine), PSI (proximal small intestine), P = 0.14 (Student’s t-test) corresponds to L. rhamnosus CNCMI– 4317 versus control (PBS).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0138880.g006: In vivo, (a) FIAF circulating level, (b) Fiaf expression in the gut, and (c) IL7. (a-c) Circulating Fiaf and Il–7 was measured using Elisa tests. (b) Fiaf expression was determined via RT-qPCR.Stars indicate p<0.05 (*) in comparison with GF control group (PBS). DSI (distal small intestine), PSI (proximal small intestine), P = 0.14 (Student’s t-test) corresponds to L. rhamnosus CNCMI– 4317 versus control (PBS).
Mentions: Germ-free mice were colonized with L. rhamnosus CNCMI–4317 strain, L. rhamnosus CNCMI–2493 (control strain) or PBS during 11 days and then sacrificed. Mice colonized with L. rhamnosus CNCMI–4317 presented an increase in the concentration of plasma FIAF as compared to control mice (Fig 6a). With regard to the Fiaf gene expression among different tissues, the Fiaf gene expression tended to increase in the distal small intestine in the presence of L. rhamnosus CNCMI–4317 (P = 0.14), but no significant differences could be observed for colonic expression (Fig 6b). Furthermore, circulating FIAF level was not correlated to the expression of Fiaf gene expression in adipose tissues nor in the liver (S3a and S3b Fig).

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