Item Details

title

ISOLATION AND CHARACTERIZATION OF LPS+ BACTERIAL EXTRACELLULAR VESICLES IN OBESITY-INDUCED GUT DYSBIOSIS MODEL: GUT-HEPATIC PORTAL VEIN-LIVER AXIS

author

Jain, Heetanshi Sanjay

abstract

An imbalance in the gut microbiome, called microbial dysbiosis, has been implicated in multiple diseases. However, the underlying mechanism linking gut dysbiosis with distant pathological changes in the body remains unclear. Extracellular vesicles (EVs) are lipid membrane bound nano-sized vesicles secreted by all cells, including bacteria. With their content protected from degradation while in circulation, these vesicles are an efficient means for short- and long-distance communication. Here, employing a well-established diet-induced obesity (DIO) gut dysbiosis model, we tracked the biodistribution of bacterial EVs (bEV) and characterized LPS+ EV in the gut-hepatic portal vein-liver axis and showed its entry into the systemic circulation. Nano particle tracking analysis (NTA) showed a significant increase in EV concentration in the hepatic portal vein plasma but no change in the cardiac plasma in obese mice compared to lean mice. Flow cytometry analysis showed that the percentage of LPS+ EVs was significantly higher in feces of obese mice compared to lean mice. Importantly, LPS+ bEV from hepatic tissue induced a strong pro-inflammatory effect in human monocytes. Overall, these results suggest that LPS+ bEV enters into circulation from the gut, absorbed in the liver, and could be responsible for the pro-inflammatory state associated with obesity-induced gut dysbiosis.

subject

Bacteria

Extracellular vesicles

Gut dysbiosis

Gut microbiome

Inflammation

Lipopolysaccharide

contributor

Deep, Gagan (advisor)

Yammani, Raghunatha (committee member)

Cook, Katherine (committee member)

date

2023-07-25T17:48:45Z (accessioned)

2024-06-06T08:30:08Z (available)

2023 (issued)

degree

Biomedical Science – MS (discipline)

embargo

2024-06-06 (terms)

identifier

http://hdl.handle.net/10339/102279 (uri)

language

en (iso)

publisher

Wake Forest University

type

Thesis