Angiotensin (1–7) delivered orally via probiotic, but not subcutaneously, benefits the gut-brain axis in older rats

Buford, Thomas W.; Sun, Yi; Roberts, Lisa M.; Banerjee, Anisha; Peramsetty, Sujitha; Knighton, Anthony; Verma, Amrisha; Morgan, Drake; Torres, Gonzalo E.; Li, Qiuhong; Carter, Christy S.

doi:10.1007/s11357-020-00196-y

Cited by 30 publications

(32 citation statements)

References 78 publications

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“…We recently published data from a short-term dosing study indicating that the Ang (1-7) GMP reduced neuroinflammatory gene expression in the pre-frontal cortex while also increasing circulating concentrations of neuroregulatory compounds picolinic acid and serotonin in older F344/BN rats (Buford et al, 2020). Our findings also indicated that the use of an Ang FIGURE 3 | Simplified schematic of human breakdown of tryptophan and influences on CNS signaling.…”

Section: Angiotensin (1-7) and The Gutmentioning

confidence: 53%

“…Thus, a different formulation-particularly one which could be administered orally-could provide practical benefits to patients from both a cost and ease of use standpoint. In line with this reasoning, our previous work has demonstrated that orally delivered Ang (1,7) GMP influences far beyond the gut, including altering levels of neurotransmitters and components of the RAS (Buford et al, 2020).…”

Section: Angiotensin (1-7) the Cns And Potential Mechanisms Through mentioning

confidence: 60%

“…Though there is ample evidence that this compound is beneficial in many ways, systemic infusion of Ang (1,7) itself is not a feasible option, as it's half-life would require a near constant infusion (Fyhrquist et al, 1976). Our previous work has demonstrated that oral administration of Ang (1,7)-expressing probiotic [Lactobacillus paracasei (LP) modified to express Ang (1-7); Ang (1-7) GMP] not only increased circulating levels of Ang (1,7), it significantly altered several components of the gut-brain-axis in ways that direct systemic Ang (1,7) administration did not (Carter et al, 2019;Buford et al, 2020). Moreover, oral administration of Ang (1,7) GMP significantly altered microbial richness and diversity within the gut, increased circulating Ang (1,7), decreased circulating AngII, and altered several metabolites of tryptophan metabolism in serum, demonstrating its ability to affect changes beyond those observed within the digestive tract where it was placed.…”

Section: Introductionmentioning

confidence: 99%

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Angiotensin (1–7) Expressing Probiotic as a Potential Treatment for Dementia

et al. 2021

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Increasing life expectancies are unfortunately accompanied by increased prevalence of Alzheimer's disease (AD). Regrettably, there are no current therapeutic options capable of preventing or treating AD. We review here data indicating that AD is accompanied by gut dysbiosis and impaired renin angiotensin system (RAS) function. Therefore, we propose the potential utility of an intervention targeting both the gut microbiome and RAS as both are heavily involved in proper CNS function. One potential approach which our group is currently exploring is the use of genetically-modified probiotics (GMPs) to deliver therapeutic compounds. In this review, we specifically highlight the potential utility of utilizing a GMP to deliver Angiotensin (1–7), a beneficial component of the renin-angiotensin system with relevant functions in circulation as well as locally in the gut and brain.

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Section: Angiotensin (1-7) and The Gutmentioning

confidence: 53%

Section: Angiotensin (1-7) the Cns And Potential Mechanisms Through mentioning

confidence: 60%

Section: Introductionmentioning

confidence: 99%

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Angiotensin (1–7) Expressing Probiotic as a Potential Treatment for Dementia

et al. 2021

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“…A previous study showed that oral administration of LP-A in rats increased abundance of gut Akkermansia muciniphila ( A. m uciniphila ). 123 As decreased abundance of A. muciniphila has been associated with increased prevalence of metabolic disorders, such as obesity and type 2 diabetes, 135 − 137 such increase in A. muciniphila by LP-A treatment, which remains to be confirmed in diabetic mice by ongoing study, may provide additional beneficial effects in diabetic animals. More comprehensive studies will be required to further understand the effects and underlying mechanisms of LP-A treatment in various tissues.…”

Section: Discussionmentioning

confidence: 99%

“…Third, unlike conventional approaches, the probiotics-based oral delivery system, using a carrier fused with the therapeutic protein, facilitates efficient transmucosal transport into the circulation, increases half-life and target tissue uptake, thus enhancing bioavailability. 39 , 122 , 123 Moreover, probiotic bacteria are inexpensive to produce and oral delivery of therapeutics is patient-friendly, thus probiotics-based approach is more cost-effective. Thus, a probiotic enriched with Ang-(1–7) represent potential therapy to improve metabolism, and intestinal and immune functions, thereby preventing DR and other diabetic complications.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin-(1–7) Expressed From Lactobacillus Bacteria Protect Diabetic Retina in Mice

Verma

Zhu

et al. 2020

Trans. Vis. Sci. Tech.

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Purpose A multitude of animal studies substantiates the beneficial effects of Ang-(1–7), a peptide hormone in the protective axis of the renin angiotensin system, in diabetes and its associated complications including diabetic retinopathy (DR). However, the clinical application of Ang-(1–7) is limited due to unfavorable pharmacological properties. As emerging evidence implicates gut dysbiosis in pathogenesis of diabetes and supports beneficial effects of probiotics, we sought to develop probiotics-based expression and delivery system to enhance Ang-(1–7) and evaluate the efficacy of engineered probiotics expressing Ang-(1–7) in attenuation of DR in animal models. Methods Ang-(1–7) was expressed in the Lactobacillus species as a secreted fusion protein with a trans-epithelial carrier to allow uptake into circulation. To evaluate the effects of Ang-(1–7) expressed from Lactobacillus paracasei (LP), adult diabetic eNOS −/− and Akita mice were orally gavaged with either 1 × 10 9 CFU of LP secreting Ang-(1–7) (LP-A), LP alone or vehicle, 3 times/week, for 8 and 12 weeks, respectively. Results Ang-(1–7) is efficiently expressed from different Lactobacillus species and secreted into circulation in mice fed with LP-A. Oral administration of LP-A significantly reduced diabetes-induced loss of retinal vascular capillaries. LP-A treatment also prevented loss of retinal ganglion cells, and significantly decreased retinal inflammatory cytokine expression in both diabetic eNOS −/− and Akita mice. Conclusions These results provide proof-of-concept for feasibility and efficacy of using engineered probiotic species as live vector for delivery of Ang-(1–7) with enhanced bioavailability. Translational Relevance Probiotics-based delivery of Ang-(1–7) may hold important therapeutic potential for the treatment of DR and other diabetic complications.

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Aortic aneurysm: pathophysiology and therapeutic options

Yang,

Khan,

Liang

et al. 2024

MedComm

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Aortic aneurysm (AA) is an aortic disease with a high mortality rate, and other than surgery no effective preventive or therapeutic treatment have been developed. The renin–angiotensin system (RAS) is an important endocrine system that regulates vascular health. The ACE2/Ang‐(1–7)/MasR axis can antagonize the adverse effects of the activation of the ACE/Ang II/AT1R axis on vascular dysfunction, atherosclerosis, and the development of aneurysms, thus providing an important therapeutic target for the prevention and treatment of AA. However, products targeting the Ang‐(1–7)/MasR pathway still lack clinical validation. This review will outline the epidemiology of AA, including thoracic, abdominal, and thoracoabdominal AA, as well as current diagnostic and treatment strategies. Due to the highest incidence and most extensive research on abdominal AA (AAA), we will focus on AAA to explain the role of the RAS in its development, the protective function of Ang‐(1–7)/MasR, and the mechanisms involved. We will also describe the roles of agonists and antagonists, suggest improvements in engineering and drug delivery, and provide evidence for Ang‐(1–7)/MasR's clinical potential, discussing risks and solutions for clinical use. This study will enhance our understanding of AA and offer new possibilities and promising targets for therapeutic intervention.

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Angiotensin (1–7) delivered orally via probiotic, but not subcutaneously, benefits the gut-brain axis in older rats

Cited by 30 publications

References 78 publications

Angiotensin (1–7) Expressing Probiotic as a Potential Treatment for Dementia

Angiotensin (1–7) Expressing Probiotic as a Potential Treatment for Dementia

Angiotensin-(1–7) Expressed From Lactobacillus Bacteria Protect Diabetic Retina in Mice

Aortic aneurysm: pathophysiology and therapeutic options

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