Figure 4.

Metabolic improvements and activation of HIF2α signaling in the duodenum following administration of probiotics that contain Lactobacillus spp. and HIF luciferase responses to lactate treatment in the organoids from HIF-reporter mice. A. Experimental design and timeline of VSL#3 study (VSL#3 n = 6, Vehicle n = 7). B. Body weight. C. Cumulative food intake. D. Intraperitoneal glucose tolerance test (I.P. GTT, 2 g/kg) and Area Under the Curve (AUC). E. Relative expressions of Hif2α and its target genes in the duodenum of VSL#3- vs. vehicle-treated mice. F. Experimental design of the ex-vivo study. G. Luciferase activity of duodenal enteroids collected from HIF-reporter mice in response to lactate treatment (10ug/ml) vs. vehicle for indicated periods (lactate: n = 8 cell extracts for 1 and 4 h of treatment, n = 16 cell extracts for 16 h of treatment; vehicle: n = 7–8 cell extracts for each period of treatment). Data are presented as means ± S.E.M. Two-way ANOVA with post hoc Sidak test for multiple comparisons (Panel B, C, and Panel D–I.P. GTT curve) and Student's t-test (Panel D-AUC, Panel E and Panel G) were used for significance assessments. ∗∗∗P < 0.001, ∗∗P < 0.01, ∗P < 0.05.