Location: Diet, Genomics and Immunology Lab
Title: Feeding probiotic Lactobacillus paracasei to Ossabaw pigs on a high fat diet prevents cholesteryl-ester accumulation and LPS modulation of the LXR and inflammatory axis in alveolar macrophages Authors
Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: June 7, 2013
Publication Date: N/A
Interpretive Summary: There has been growing interest in the immune-modulating effects of intestinal microbes and particularly some strains of lactic acid producing probiotic bacteria on metabolic systems. A number of human and animal studies have demonstrated that supplementation with some probiotic bacterial can lower serum cholesterol levels by decreasing recirculation of bile acids and cholesterol to the liver. There is little characterization of the systemic effects of probiotics on cholesterol metabolism in extra-hepatic tissue, but the recent evidence that probiotics can modulate cholesterol absorption through interactions with Liver X receptors (LXR) supports a role in cholesterol metabolism and gene expression of the LXR axis in cell types outside of the gut. There is a paucity of data on the potential effects of probiotic supplementation on metabolic and inflammatory parameters in alveolar macrophage (AM) cells isolated from the lungs; although this is an important cell for controlling disease causing organisms and pollutants. The current study examined whether AM isolated from juvenile Ossabaw pigs, a model that simulates human metabolic syndrome, fed either a high fat of high fat diet supplemented with the probiotic Lactobacillus paracasei changed cholesterol metabolism and expression of LXR and inflammatory related genes and proteins in AM. This information is important to nutritionists and health care professionals who study the benefits of diet in maintenance of good health.
Technical Abstract: Liver X receptors (LXR) play an integral role in regulation of cholesterol metabolism and the inflammatory response, and high fat (HF) diets and microbial infection can antagonize the LXR pathway leading to accumulation of cholesteryl-esters (CE) and increased expression of pro-inflammatory mediators in macrophages. The probiotic bacteria Lactobacillus paracasei possesses cholesterol lowering and immune modulating properties when added to the diet. Therefore, the present study sought to model whether daily feeding of L. paracasei to juvenile Ossabaw pigs fed a HF diet could modulate cholesterol metabolism and the LXR/inflammatory axis in LPS-stimulated alveolar macrophages (AM). The results showed that AM isolated from pigs fed an HF diet had significantly higher concentrations of CE compared to AM from pigs fed a control (C) basal diet, but not in pigs fed a HF diet and given L. paracasei (HFPB). Ex vivo stimulation of AM with LPS significantly opposed LXR agonist-mediated transcription of cholesterol metabolism genes: ABCA1, CH25H, and PPAR' in pigs on the C diet, and LXRa, ABCA1, ABCG1, CH25H, and PPAR' in pigs on the HF diet. This transcriptional effect was abrogated for all these genes except LXRa in AM from pigs given L. paracasei. We observed that AM from pigs fed a HF diet had a significantly higher IL-1ß mRNA response to LPS, but this was not affected by L. paracasei. However, protein analysis of cell culture supernatants revealed that AM from HFPB-fed pigs had significantly lower LPS-induced protein expression of IL-1ß than AM from HF-fed pigs. Moreover, AM from pigs fed the C diet and given L. paracasei (CPB), had significantly higher mRNA levels of IL-8, IL-6, and IL-10 in response to LPS. These data demonstrated a role for L. paracasei in modulating AM cholesterol metabolism and the response to LPS.