Engineered Gut Bacteria as a Form of Therapy

The gut microbiome appears important to health, as judged by the changes in relative population sizes between species that take place across the course of aging, and the ability of reversing those changes to improve health and extend life in old animals. If the near future is restoration of a more youthful balance of microbial populations in the aged gut microbiome, to produce more beneficial metabolites and reduce inflammation, then the next step after that is to start engineering gut microbes to produce even greater effects. The example here produces poor, sex-specific effects in rats, but it is one example of a thousand different possibilities, many of which will turn out to be far more impressive.

Engineered gut microbiota represents a new frontier in medicine, in part serving as a vehicle for the delivery of therapeutic biologics to treat a range of host conditions. The gut microbiota plays a significant role in blood pressure regulation; thus, manipulation of gut microbiota is a promising avenue for hypertension treatment. In this study, we tested the potential of Lactobacillus paracasei, genetically engineered to produce and deliver human angiotensin converting enzyme 2 (Lacto-hACE2), to regulate blood pressure in a rat model of hypertension with genetic ablation of endogenous Ace2 (Ace2-/- and Ace2-/y).

Our findings reveal a sex-specific reduction in blood pressure in female (Ace2-/-) but not male (Ace2-/y) rats following colonization with the Lacto-hACE2. This beneficial effect of lowering blood pressure was aligned with a specific reduction in colonic angiotensin II, but not renal angiotensin II, suggesting the importance of colonic Ace2 in the regulation of blood pressure. We conclude that this approach of targeting the colon with engineered bacteria for delivery of ACE2 represents a promising new paradigm in the development of antihypertensive therapeutics.


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