Methionine Enterorecirculation and SYNB1353 Consumption

Example 13

The objectives of this study were to determine (1) whether enterorecirculation of methionine occurs, and (2) whether orally-administered SYNB1353 can consume peripherally administered (IP) labeled methionine in mice.

In a first study, healthy male C57BL/6 mice (n=3/group) were fasted overnight and received a single IP dose of D4-methionine (100 mg/kg). Blood and gut effluents (SI, cecum or colon) were collected at 0, 0.5, 1, or 2 hours post dosing for D4-methionine measurements. Results shown in FIGS. 19A-19D indicate that there is enterorecirculation of methionine from the plasma into the gut.

In a second study, healthy male C57BL/6 mice (n=10-18/group) were fasted overnight and received a single IP dose of D4-Met (100 mg/kg) followed by 2 doses of SYNB1353 PO 0.5 and 1.5 hours later. Blood and urine were collected for D4-Met, D4-tHcy and D4-3-MTP measurements. Results are shown in FIGS. 20A-20C and illustrate that SYNB1353 is capable of consuming peripherally-administered labeled methionine and blunts plasma labeled methionine and labeled homocysteine levels.