Serotonin Transporter Deficiency Induces Metabolic Alterations in the Ileal Mucosa.

Serotonin transporter (SERT) deficiency has been implicated in metabolic syndrome, intestinal inflammation, and microbial dysbiosis. Interestingly, changes in microbiome metabolic capacity and several alterations in host gene expression, including lipid metabolism, were previously observed in SERT-/- mice ileal mucosa. However, the precise host or microbial metabolites altered by SERT deficiency that may contribute to the pleiotropic phenotype of SERT KO mice are not yet understood. This study investigated the hypothesis that SERT deficiency impacts lipid and microbial metabolite abundances in the ileal mucosa, where SERT is highly expressed. Ileal mucosal metabolomics was performed by Metabolon on wild-type (WT) and homozygous SERT knockout (KO) mice. Fluorescent-activated cell sorting (FACS) was utilized to measure immune cell populations in ileal lamina propria to assess immunomodulatory effects caused by SERT deficiency. SERT KO mice exhibited a unique ileal mucosal metabolomic signature, with the most differentially altered metabolites being lipids. Such changes included increased diacylglycerols and decreased monoacylglycerols in the ileal mucosa of SERT KO mice compared to WT mice. Further, the ileal mucosa of SERT KO mice exhibited several changes in microbial-related metabolites known to play roles in intestinal inflammation and insulin resistance. SERT KO mice also had a significant reduction in the abundance of ileal group 3 innate lymphoid cells (ILC3). In conclusion, SERT deficiency induces complex alterations in the ileal mucosal environment, indicating potential links between serotonergic signaling, gut microbiota, mucosal immunity, intestinal inflammation, and metabolic syndrome.

Association Between Uveal Melanoma and Allostatic Load.

BACKGROUND/AIM: Allostatic load (AL) is a measure of chronic stress that is associated with worse cancer outcomes. The purpose of this retrospective cohort study was to investigate the relationship between AL and uveal melanoma (UM) clinical features. PATIENTS AND METHODS: AL score was calculated as a composite of ten biomarkers in 111 patients with UM from the University of Illinois Hospital. One point was assigned to an AL score for each biomarker based on predetermined cutoff values. Linear and logistic regression analyses evaluated the relationship between AL score and several tumor clinical characteristics. RESULTS: High AL score had a significant relationship with extraocular extension (p=0.015). There was also a significant difference in mean blood glucose levels between the different tumor size groups (p=0.029). Higher AL scores also had a trend of being associated with a smaller tumor size (p=0.069). CONCLUSION: AL score was significantly associated with the presence of extraocular extension for uveal melanoma, while the smallest tumor size group was associated with the highest blood glucose level. No other significant correlations were found between AL and other clinical features of UM. The relationship between AL score and extraocular extension warrants further investigation. Additional research is needed to evaluate socioeconomic factors and their effect on the relationship between chronic stress and the clinical features of UM.