"Revolutionizing Hypertension Treatment: Dr. Bina Joe's Groundbreaking Study on Harnessing Microbiota for Optimal Blood Pressure"
"Explore the groundbreaking research by Dr. Bina Joe, revealing how engineered bacteria in our gut can combat hypertension. Discover the gender-specific insights, the role of ACE2, and the promising potential of microbiota in improving overall health."
DR T S DIDWAL MD
1/20/20245 min read
Engineered gut bacteria producing human ACE2 protein may offer a new approach to treating hypertension, according to a new study published in the journal Pharmacological Research. The engineered bacteria reduced blood pressure in female rats with hypertension but not in males. This effect was linked to lower levels of a blood pressure-raising molecule in the colon. The study suggests that this approach could be a promising new way to treat hypertension, but more research is needed.
Key Points
Engineered gut bacteria offer a novel way to deliver therapeutics like proteins.
The gut microbiome influences blood pressure, and manipulating it could offer new treatments for hypertension.
Approach:
This study tested whether Lactobacillus paracasei bacteria, genetically modified to produce human angiotensin-converting enzyme 2 (ACE2) (called Lacto-hACE2), could regulate blood pressure in genetically hypertensive rats lacking their ACE2 (Ace2-/- and Ace2-/y).
Key findings:
Lacto-hACE2 colonization reduced blood pressure in female Ace2-/- rats but not male Ace2-/y rats.
This beneficial effect was associated with a decrease in colonic angiotensin II, a molecule that increases blood pressure.
Renal angiotensin II levels remained unchanged, suggesting colonic ACE2 activity specifically impacts blood pressure.
Significance:
This study demonstrates the potential of engineered bacteria delivering ACE2 directly to the colon as a new strategy for treating hypertension.
The sex-specific effect requires further investigation but suggests potential for personalized medicine approaches.
Details:
The study focused on genetically hypertensive rats, which may not fully reflect human hypertension.
The long-term efficacy and safety of lacto-hACE2 treatment need further assessment.
The potential side effects of colonic ACE2 overexpression and any interactions with existing medications need to be investigated.
Future directions:
Larger clinical trials are needed to confirm the effectiveness and safety of lacto-hACE2 in humans.
Research should explore the mechanisms behind the sex-specific effect and tailor treatments accordingly.
Combining lacto-hACE2 with other antihypertensive approaches could be explored for synergistic benefits.
IThe landscape of medical innovation has been reshaped by the emergence of engineered gut microbiota, representing a revolutionary frontier in healthcare. Acting as a vehicle for therapeutic biologics, these microorganisms hold immense potential in treating various host conditions. In a groundbreaking study, we explore the transformative role of genetically engineered Lactobacillus paracasei in delivering human angiotensin-converting enzyme 2 (Lacto-hACE2) for the regulation of blood pressure.
The Link Between Gut Microbiota and Blood Pressure Regulation
A Promising Approach for Hypertension Treatment
Recent studies highlight the significant involvement of gut microbiota in blood pressure regulation. The manipulation of gut microbiota emerges as a promising avenue for the treatment of hypertension, a prevalent health concern. This investigation focuses on the potential of Lactobacillus paracasei, genetically engineered to produce Lacto-hACE2, to regulate blood pressure in a rat model with genetic ablation of endogenous Ace2.
Sex-Specific Reduction in Blood Pressure
These findings present a noteworthy sex-specific reduction in blood pressure, particularly in female rats with Ace2 genetic ablation. The administration of lacto-hACE2 demonstrated a clear benefit in lowering blood pressure, aligning with a specific reduction in colonic angiotensin II. This underscores the pivotal role of colonic Ace2 in blood pressure regulation, revealing a promising paradigm for antihypertensive therapeutics.
Targeting the Colon: A Novel Approach
Engineered Bacteria for ACE2 Delivery
Intriguingly, this study introduces a novel approach of targeting the colon with engineered bacteria for the delivery of ACE2. This innovative strategy presents a promising avenue in the development of antihypertensive therapeutics. The oral administration of Lacto-hACE2 effectively lowered blood pressure in female rats with Ace2 genetic ablation, marking a significant breakthrough in hypertension treatment.
Understanding the Role of Ace2 in Sex-Specific Hypertension
Unveiling the X Chromosome Connection
The Ace2 gene, situated on the short arm of the X chromosome, has been implicated in sex-specific hypertension due to its role in downregulating angiotensin II. The hypothesis centered around disrupting Ace2 to induce hypertension and subsequently administering beneficial gut microbiota expressing ACE2 to prevent it. The generation of a novel Ace2 CRISPR/Cas9 gene-edited rat model validated this hypothesis, showing elevated blood pressure in both male and female Ace2 KO rats.
Sex-Specific BP Rescue: A Key Insight
Remarkably, the oral delivery of ACE2 via lacto-hACE2 rescued high blood pressure exclusively in female rats. This sex-specific BP rescue was associated with reduced colonic angiotensin II levels, highlighting the importance of colonic Ace2 in blood pressure regulation. These results shed light on the intricate mechanisms of sex-specific hypertension and the potential of microbiome-based medicine.
Unraveling Sex-Specific Mechanisms of Blood Pressure Regulation
Disparities in the Renin-Angiotensin System
Recent years have witnessed a growing interest in understanding sex-specific mechanisms of blood pressure regulation. Sex differences in the renin-angiotensin system (RAS) and its downstream effectors have been revealed. The study aligns with the notion that the activation arm of the RAS (AngII) is more crucial in males, while the protective arm (ACE2, Ang1–7) plays a pivotal role in females.
Implications for Antihypertensive Therapies
Clinical evidence supports the disparity in the prescription of antihypertensive therapies between males and females. The disruption of ACE2 resulted in a more pronounced increase in blood pressure in female rats, emphasizing the significance of the protective arm of the RAS. The successful restoration of ACE2 through lacto-hACE2 intervention rescued high blood pressure in females, offering a potential explanation for the observed sex-specific BP rescue effect.
The Role of Colonic Angiotensin II and Glucose Metabolism
Microbial Interventions and Glycolysis
This study delves into the intriguing connection between rescued high blood pressure in females and reduced colonic angiotensin II levels. Lacto-hACE2, primarily accumulated in the gut, influenced colonic AngII and AngII-induced glucose metabolism. The examination of glycolysis-related genes revealed inhibited expression in lacto-hACE2-treated female rats, providing a comprehensive understanding of the microbial influence on blood pressure regulation.
Microbiome-Based Medicine: A Glimpse into the Future
Expanding Horizons with Probiotics
The realm of microbiome-based medicine is expanding, with probiotics emerging as a therapeutic avenue for hypertension. Lactobacillus, a beneficial microbe, has demonstrated its ability to decrease blood pressure in both rats and humans. This study contributes to this evolving field by showcasing the effectiveness of engineered Lactobacillus paracasei expressing human ACE2 in ameliorating hypertension in a novel Ace2 KO rat model.
Conclusions: A Triad of Key Findings
In conclusion, This study unravels three pivotal findings: the efficacy of engineered commensal bacteria in delivering antihypertensive biologics; the specific effectiveness of Lactobacillus paracasei engineered with human ACE2; and the mechanism behind the sex-specific blood pressure reduction in female rats. This research paves the way for future developments in microbiome-based medicine, offering hope for innovative approaches to hypertension treatment.
To Summarize
Paradigm Shift in Hypertension Research: Published in the prestigious journal Pharmacological Research, Dr. Bina Joe's study marks a paradigm shift in understanding how microbiota can combat hypertension.
Microbiota as a Health Ally: Dr. Joe's conclusive evidence demonstrates that microbiota can be harnessed to significantly improve health, particularly in terms of optimal blood pressure.
Proof of Principle: Dr. Joe's pioneering work with Lactobacillus paracasei modified to produce ACE2 serves as a proof of principle that microbiota can be utilized to create products that improve health measurably.
Gender-Specific Response: The study reveals a gender-specific response to the engineered bacteria, with blood pressure reduction observed only in female rats, highlighting the intricate connection between gender and microbiota influence.
ACE2's Role Beyond COVID-19: Beyond its role in COVID-19, ACE2's negative regulation of the renin-angiotensin system is crucial in lowering blood pressure, presenting a multifaceted therapeutic potential.
Bridge Between Theory and Application: Dr. Joe emphasizes that the findings bridge the gap between theory and clinical application, providing a ray of hope for leveraging bacteria to treat hypertension and chronic conditions.
Potential for Microbiome Medicine: The research opens doors for microbiome medicine, offering a real possibility to correct hypertension and potentially address other health challenges by harnessing the power of bacteria.
Journal Reference:
Mei, X., Mell, B., Aryal, S., Manandhar, I., Tummala, R., Zubcevic, J., Lai, K., Yang, T., Li, Q., Yeoh, B. S., & Joe, B. (2023, October 1). Genetically engineered Lactobacillus paracasei rescues colonic angiotensin converting enzyme 2 (ACE2) and attenuates hypertension in female Ace2 knock out rats. Pharmacological Research. https://doi.org/10.1016/j.phrs.2023
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