Intestinal goblet cell and mucus alterations in obesity

Obesity is associated with changes of the intestinal microbiota, but factors that govern this are largely undefined. We hypothesized that altered intestinal goblet cell function contribute to microbiota changes in obesity. Goblet cell numbers and mucus thickness were quantified in jejunal biopsies of eleven obese and five normal weight human subjects (BMI 45.6±1.9 vs. 25.0±1.7kg/m²) as well as obese and lean ZDF rats (weight: 350±7 vs. 305±5g, n=6 in both groups) using histological and immunohistochemical techniques. Expression of mucus components and differentiation factors such as FCGBP, REG3-gamma and Klf4 were analyzed by qPCR. The total number of fecal bacteria and translocation as well as the relative abundance of phyla and mucus-associated bacteria were determined by qPCR. Bacteria were localized by FISH targeting 16S rDNA and muc2. Obese subjects and rats displayed reduced jejunal goblet cell numbers compared with lean controls (6.4±0.4 vs. 8.1±0.2 cells/100μm villus, p<0.05 and 8.4±0.6 vs. 10.6±0.4 cells/100μm villus, p<0.01, respectively). Klf4  expression was lower in the jejunum and colon (0.22±0.05 vs. 0.61±0.07, p<0.01 and 0.40±0.05 vs. 0.60±0.05, p<0.05, respectively). Muc2 staining intensity and gene expression were reduced in the colon of obese rats (0.97±0.17 vs. 1.50±0.19, p<0.05). Bacteria appeared to be dispersed throughout the compromised mucus layer of obese rats, and were found in close proximity to epithelial cells. Interestingly, colonic Muc2 gene expression correlated with the abundance of both Firmicutes (r_s=-0.70, p<0.05) and A.muciniphila (r_s=0.78, p<0.05). Altogether, the mucus barrier is compromised in obesity, which could contribute to the observed microbiota composition changes and promote bacterial translocation.