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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 .

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