(P14-016-24) Impact of Fecal Microbial Transplant Donor Inflammatory Phenotype on Tissue Inflammation in Humanized Mouse Models After a High-Fat Diet

Objectives: High-fat diets (HFD) can induce low-grade inflammation and obesity-related pathologies. While there is research on the inflammatory effects of HFDs and their role in obesity-related pathologies, there remains a gap in understanding the impact of donor inflammation status on inflammation, particularly in humanized mouse models after an HFD. The aim of this pilot study was to investigate how donor inflammation status impacts inflammation in the metabolically active tissues in humanized mice after an HFD.

Methods: Germ-free mice received a fecal transplant from one of two human stool donors that were metabolically similar but differed in systemic inflammation (low, high). Mice underwent a 6-week HFD (40.6% fat) rich in sugars and trans-fatty acids. After sacrifice, liver and muscle tissues were harvested for RNA extraction and quantitative PCR (qPCR). qPCR yielded threshold cycle (CT) values for genes of interest (C-Reactive Protein, CRP; Interleukin, IL-10, IL-1ß, IL-6). The 2^-ΔCT was calculated to determine the relative expression of the target gene(s) to a housekeeping gene. The fold change of observed differences of high and low donor phenotypes was used, given the small pilot sample size (n =13).

Results: In liver tissue, inflammatory gene expression had a fold change (2^-ΔCT high/2^-ΔCT  low) for CRP of 1.3-fold, IL-10 of 6.9-fold, and IL-1ß of 3.1-fold. In muscle, mice also had a fold change for IL-6 of 3.9-fold (n=8).

Conclusions: Cytokine expression in the liver and muscle of humanized mice on an HFD was donor-dependent. These data provide preliminary evidence that inflammation phenotype may be transferred with the gut microbiota and that low-inflammatory phenotypes may protect against the inflammatory effects linked with a high-fat diet, opening new avenues for further investigation into potential strategies for inflammation management associated with HFD and its related complications.

Funding Sources: USDA-NIFA