Fig. 4: Blood Phe lowering a human gut-chip model with administration of SYN5183. | Nature Communications

Fig. 4: Blood Phe lowering a human gut-chip model with administration of SYN5183.

From: Characterization of an engineered live bacterial therapeutic for the treatment of phenylketonuria in a human gut-on-a-chip

Fig. 4

a Schematic of study design. A single dose of SYN5183 was administered in the gut compartment, while 1.0 mM Phe was administered continuously to the blood compartment. SYN5183 CFU was enumerated from gut compartment effluents, and Phe and TCA were quantified using effluents collected from the gut and blood compartments. (b–d, n = 3 gut chips) Concentrations of SYN5183 (b; CFU/mL), Phe (c; mM), and TCA (d; mM) recovered from gut compartment effluents over time. (e, n = 3 gut chips) Concentrations of Phe (mM) recovered from blood compartment effluents over time. f Area under the curve (AUC; mM-hr) of Phe recovered from blood compartment effluents over 12 h. (g, h, n = 3 gut chips, villus height measurements were acquired from 4 ROIs per image) Villus height (μm) and apparent permeability (Papp; cm/s) across the gut barrier 12 h post-dose. For (b–h), H, M, and L correspond to SYN5183 doses of 1.25 × 109 CFU/mL, 6.25 × 108 CFU/mL, and 1.25 × 108 CFU/mL, respectively. NT corresponds to non-treated chips. *p < 0.05; 2-way ANOVA, with a post-hoc Tukey analysis using a 95% confidence interval compared to the NT group, error bars represent SEM with the middle point representing the mean value. Source data are provided as a Source Data file.

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