Genetically engineered Lactobacillus paracasei rescues colonic angiotensin converting enzyme 2 (ACE2) and attenuates hypertension in female Ace2 knock out rats

Mei, Xue; Mell, Blair; Aryal, Sachin; Manandhar, Ishan; Tummala, Ramakumar; Zubcevic, Jasenka; Lai, Khanh; Yang, Tao; Li, Qiuhong; Yeoh, Beng San; Joe, Bina

doi:10.1016/j.phrs.2023.106920

Cited by 3 publications

(2 citation statements)

References 57 publications

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“…to overexpress human angiotensin-converting enzyme 2 demonstrated BP-lowering effects in a sex-specific manner. 138 This was the first demonstration of successfully utilizing precisely edited bioengineered bacteria to deliver an antihypertensive agent. With the currently approved therapies and medications for the management of hypertension, it is estimated that only a quarter of hypertensive individuals achieve control over their BP.…”

Section: Opportunitiesmentioning

confidence: 99%

Prospects for Leveraging the Microbiota as Medicine for Hypertension

Durgan,

Zubcevic,

Vijay-Kumar

et al. 2024

Hypertension

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Section: Opportunitiesmentioning

confidence: 99%

Prospects for Leveraging the Microbiota as Medicine for Hypertension

Durgan,

Zubcevic,

Vijay-Kumar

et al. 2024

Hypertension

Self Cite

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“…[1,5] Recently innovative research conducted by Xue mei et al, tested Lactobacillus paracasei, a beneficial gut bacterium, that was specially modified to produce a protein called ACE2 in laboratory rats that are predisposed to hypertension and unable to naturally produce ACE2, demonstrated lowering of blood pressure. [6] A meta-analysis suggested a beneficial effect of probiotics on BP by a modest degree, especially in the diabetes mellitus and hypertension. However, prolonging the duration of treatment could not improve the beneficial antihypertensive effect.…”

Section: Sirmentioning

confidence: 99%

Efficacy and Challenges in Usage of Gut Microbiome in Management of Hypertension

Rao,

Varne

2024

Int. J. Clinical and Exp. Physiol.

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Salt-Responsive Gut Microbiota Induces Sex-Specific Blood Pressure Changes

Bardhan,

Mei,

Lai

et al. 2024

Circulation Research

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BACKGROUND: Tryptophan metabolism is important in blood pressure regulation. The tryptophan-indole pathway is exclusively mediated by the gut microbiota. ACE2 (angiotensin-converting enzyme 2) participates in tryptophan absorption, and a lack of ACE2 leads to changes in the gut microbiota. The gut microbiota has been recognized as a regulator of blood pressure. Furthermore, there is ample evidence for sex differences in the gut microbiota. However, it is unclear whether such sex differences impact blood pressure differentially through the tryptophan-indole pathway. METHODS: To study the sex-specific mechanisms of gut microbiota-mediated tryptophan-indole pathway in hypertension, we generated a novel rat model with Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats–associated protein 9)–targeted deletion of Ace2 in the Dahl salt-sensitive rat. Cecal microbiota transfers from donors of both sexes to female S recipients were performed. Also, Dahl salt-sensitive rats of both sexes were orally gavaged with indole to investigate blood pressure response. RESULTS: The female gut microbiota and its tryptophan-indole pathway exhibited greater buffering capacity when exposed to tryptophan, due to Ace2 deficiency, and salt. In contrast, the male gut microbiota and its tryptophan-indole pathway were more vulnerable. Female rats with male cecal microbiota responded to salt with a higher blood pressure increase. Indole, a tryptophan-derived metabolite produced by gut bacteria, increased blood pressure in male but not in female rats. Moreover, salt altered host-mediated tryptophan metabolism, characterized by reduced serum serotonin of both sexes and higher levels of kynurenine derivatives in the females. CONCLUSIONS: We uncovered a novel sex-specific mechanism in the gut microbiota-mediated tryptophan-indole pathway in blood pressure regulation. Salt tipped the tryptophan metabolism between the host and gut microbiota in a sex-dependent manner. Our study provides evidence for a novel concept that gut microbiota and its metabolism play sex-specific roles in the development of salt-sensitive hypertension.

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Genetically engineered Lactobacillus paracasei rescues colonic angiotensin converting enzyme 2 (ACE2) and attenuates hypertension in female Ace2 knock out rats

Cited by 3 publications

References 57 publications

Prospects for Leveraging the Microbiota as Medicine for Hypertension

Prospects for Leveraging the Microbiota as Medicine for Hypertension

Efficacy and Challenges in Usage of Gut Microbiome in Management of Hypertension

Salt-Responsive Gut Microbiota Induces Sex-Specific Blood Pressure Changes

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