Degree

Doctor of Philosophy (PhD)

Department

Nutrition and Food Sciences

Document Type

Dissertation

Abstract

Type 2 diabetes (T2D) affects more than 23 million individuals in the US and more than 415 million individuals worldwide. Increasing evidence suggests a strong association between gut intestinal dysbiosis and diabetes development and progression. The colonization of the gut with maladaptive and pathogenic microbiota is known as “gut dysbiosis”. T2D patients with high intestinal permeability “leaky gut” compared to healthy individuals are often unable to ferment ingested dietary fibers the way healthy individuals would do. A decrease in short chain fatty acids (SCFA) affects tight-junction protein expression, contributing to increased intestinal permeability. SCFAs such as sodium propionate (NaP) is a postbiotic metabolite of dietary fiber that can also be ingested from exogenous dietary sources. This study focuses on the ingestion of NaP to modulate inflammation in T2D patients by determining the ex-vivo efficacy of postbiotic NaP on the biomarkers of inflammation in peripheral blood mononuclear cells (PBMCs) from T2D patients. PBMCs were cultured with palmitate (0.5mM) and LPS 1ug/ml to induce pro-inflammatory cytokines. Palmitate and LPS cultured PBMC cells were treated with different concentrations of NaP (0.5 mM, 1mM, 2.5mM, 5 mM, or 40ng/ml). TNF-α, IL-1β, IL-6, IP-10, Rantes, IL-12, IL-18, and IL-10 secretions were detected by multiplex ELISA. Gene expression of these cytokines was analyzed by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). Among the four treatments, propionate at 2.5mM best protected the PBMC cells by inhibiting the secretion of pro-inflammatory cytokines, whilst increasing the secretion of the IL-10 in the cells. At the gene level, NaP at 5mM significantly increased the levels of IL-10 by 1.7 fold in both models with a significant difference from metformin. NaP did not show inhibition of pro-inflammatory cytokines (TNF-α and Rantes (CCL5) at the gene level. Further ex-vivo and clinical trials are needed to confirm these results.

Date

12-14-2020

Committee Chair

Losso, Jack

Available for download on Saturday, December 11, 2027

Share

COinS