Key result
Germ-free mice show increased fecal ACE and ACE2 activity, indicating microbiota-related intestinal shedding mechanisms.
Why the study?
ACE and ACE2 are present in the gastrointestinal tract and may interact with gut microbiota, but the origin of fecal ACE and ACE2 activity remained unclear.
Fecal ACE and ACE2 activity originates from both intestinal shedding and microbiota-related mechanisms, suggesting the gut environment modulates luminal RAAS activity.
Fecal ACE/ACE2 may mark intestinal shedding in mice; leaves open translation to human gut-RAAS monitoring or biomarkers.
Angiotensin-converting enzymes (ACE and ACE2) are key components of the renin–angiotensin–aldosterone system (RAAS) and are present in the gastrointestinal tract and intestinal content, preserving their catalytic activity, and may interact with the gut microbiota. The present study aimed to determine the origin of fecal ACE and ACE2 activity. Fecal pellets from germ-free, ACE and ACE2 knockout (KO) mice, and from the corresponding controls were analyzed using fluorimetric enzyme activity assays. ACE activity was assessed using Hippuryl-His-Leu and Z-Phe-His-Leu as substrates; ACE2 activity was assessed using Mca-APK (Dnp), with and without the ACE2 inhibitor MLN-4760. Germ-free mice showed increased fecal ACE and ACE2 activity compared to controls. ACE2-KO mice lacked fecal ACE2 activity, whereas ACE activity was unaffected. In ACE-KO mice, fecal ACE activity was reduced, but not abolished, while ACE2 activity remained similar to controls. In ACE C- and N-domain KO mice, ACE activity was similar to controls, and inhibition with captopril completely abolished fecal ACE activity using Hippuryl-His-Leu, but not Z-Phe-His-Leu, in those animals. These findings indicate that fecal ACE and ACE2 activity results from combined intestinal shedding and microbiota-related mechanisms, supporting a modulatory role of the gut environment on luminal RAAS activity.
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Ferreira‐Duarte et al. (2026) studied Origin of fecal ACE and ACE2 activity. Germ-free status and genetic knockout (ACE, ACE2, ACE C- and N-domain) vs. Corresponding control mice was evaluated on Fecal ACE and ACE2 activity. Germ-free mice showed increased fecal ACE and ACE2 activity compared to controls, indicating that fecal activity results from combined intestinal shedding and microbiota-related mechanisms.
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