(OR36-07-24) Intestinal and Hepatic Histology Are Altered by Soluble Fiber Consumption in an FXR-Dependent Manner

Objectives: Farnesoid X recepteor (FXR) is a nuclear bile acid (BA) receptor with multiple physiological functions across disparate organ systems. Such functions include regulation of BA synthesis, BA trafficking, and cellular proliferation, which highly influences function of organs such as the intestine and liver. However, BA composition varies across the gut-liver axis, thus influencing FXR activation and function. Furthermore, dietary modification, particularly fiber consumption, alters host and microbial BA metabolism. The objective of this study was to understand how soluble fiber alters enterohepatic histology in an FXR-dependent manner.

Methods: A total of (N=46) 9–10-month-old mice were utilized in a 2x2x2 study design (diet by genotype by sex). One of the two following diets was fed for a total of two weeks: a fiber-free diet (FFD) vs a 10% beta-glucan, 10% cellulose diet (BG). Genotypes included wild type (WT) vs FXR-SHP double knock out mice (DKO). Hematoxylin and eosin staining was used to identify crypt depth and villus height morphology along the gastrointestinal tract. Liver histology was examined using Halls bile and trichrome staining.

Results: Bile staining indicated more hepatic bile accumulation in WT-FFD vs all other groups (all p < 0.05). Trichrome staining demonstrated less collagen formation in WT-BG compared to all other groups (all p < 0.05). Ileum villus height and crypt depth were higher in DKO vs WT (p=0.004 and p=0.003 respectively), and females compared to males (p=0.03 and p=0.007 respectively). Cecum crypt depth was lower in WT-FFD vs all other groups (all p < 0.05). Distal colon crypt depth was lower in WT-BG vs all other groups (all p < 0.05).

Conclusions: Both hepatic and intestinal histology were impacted by soluble fiber consumption in both segment and FXR-dependent manners. This highlights the importance of FXR signaling on the structure and function of the enterohepatic axis. Ongoing studies are investigating expression of genes regulated by FXR related to gut-liver axis physiology.

Funding Sources: University of Illinois at Urbana-Champaign