The possible role of b. thetaiotaomicron-derived outer membrane vesicles (omvs) in the modulation of cholesterol uptake and diet-induced obesity

Sara Ahmadi badi,1 Seyed davar siadat,2,* Arfa moshiri,3 Fatemeh ettehad marvastti,4 Seyede fatemeh sadati khalili,5

2. Microbiology Research Center 2Mycobacteriology and Pulmonary Research Department, Pasteur Institute of Iran, Tehran, Ira

Abstract


Introduction

Altered gut microbiota composition has been proven to be associated with several disorders including metabolic syndrome. metabolic syndrome is defined by many factors such as obesity and impaired cholesterol homeostasis. various cholesterol transporters of enterocytes determine cholesterol uptake. these transporters are under control of several transcriptional factors including liver x receptor (lxr). niemann-pick c1-like 1 (npc1l1) is an important apical cholesterol transporter of enterocytes which is downregulated by lxr. also, atp-binding cassette (abc) transporters such as abca1 and abcg5/abcg8 are regulated by lxr. according to the importance of b. thetaiotaomicron and its outer membrane vesicles (omvs) in gut microbiota-host interaction, we studied the effects of b. thetaiotaomicron and its omvs on cholesterol transposition in caco-2 cell line.

Methods

Omvs extracted by sequential centrifugation. omvs physicochemical properties were confirmed using sem and sds-page. caco-2 cell line was treated with b. thetaiotaomicron and its omvs. the transcripts of lxra, lxrb, abca1, and npc1l1 were assayed using qpcr.

Results

b. thetaiotaomicron produced spherical shape omvs with a diameter ranging 30-110 nm and protein bands patterns between 17-245 kda. our data demonstrated that b. thetaiotaomicron and its omvs have the same effect on lxra, lxrb, abca1 and npc1l1 gene expression. interestingly the lxra mrna level was significantly increased while lxrb, abca1, and npc1l1 gene expression were significantly decreased in caco-2 cells.

Conclusion

We propose the existence of a possible connection between putative decreased bacteroidets and metabolic syndrome. finally, restoration of gut microbiota pattern towards bacteroidets could be valuable to reduce total serum cholesterol level and obesity.

Keywords

B. thetaiotaomicron , omv cholesterol homeostasis, npc1l1, lxr, abca1 and abcg5/abcg8