Genetic deletion of the angiotensin-(1–7) receptor Mas leads to alterations in gut villi length modulating TLR4/PI3K/AKT and produces microbiome dysbiosis

Oliveira, Luis Paulo; Guimarães, Victor Hugo Dantas; Oliveira, Janaína Ribeiro; Guimarães, André Luiz Sena; Paula, Alfredo Maurício Batista de; Bäder, Michael; Santos, Robson Augusto Souza; Santos, Sérgio Henrique Sousa

doi:10.1016/j.npep.2020.102056

Cited by 22 publications

(19 citation statements)

References 72 publications

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“…At least, in theory, it may be the altered activation of GI RAS during inflammation that makes the intestinal habitat more propathogenic. The already mentioned study by Oliveira et al ( 67 ) demonstrated that MAS receptor deletion produced dysbiosis, which was associated with increased proliferation and cell inflammation, most likely due to overproduction of LPS.…”

Section: Ras and Gut Microbiota In Health And Diseasementioning

confidence: 88%

“…Since angiotensin (1-7) has been shown to increase jejunal tryptophan absorption (66), it may similarly modulate the gut microbiome. In this regard, a very recent study by Oliveira et al (67) showed that deletion of MAS, angiotensin (1-7) receptor, in mouse model produced lower neutral amino acids absorption and changes in the gut microbiome. Specifically, the malnourishment profile leads to a compensatory increase in intestinal villi length and an unfavorable shift in bacterial composition.…”

Section: Absorption and Digestionmentioning

confidence: 99%

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Gut microbiota and renin-angiotensin system: a complex interplay at local and systemic levels

Jaworska

Koper

Ufnal

2021

American Journal of Physiology-Gastrointestinal and Liver Physi

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Gut microbiota is a potent biological modulator of many physiological and pathological states. The renin-angiotensin system (RAS), including the local gastrointestinal RAS (GI RAS), emerges as a potential mediator of microbiota-related effects. The RAS is involved in cardiovascular system homeostasis, water-electrolyte balance, intestinal absorption, glycemic control, inflammation, carcinogenesis and aging-related processes. Ample evidence suggests a bidirectional interaction between the microbiome and RAS. On the one hand, gut bacteria and their metabolites may modulate GI and systemic RAS. On the other hand, changes in the intestinal habitat caused by alterations in RAS may shape microbiota metabolic activity and composition. Notably, the pharmacodynamic effects of the RAS-targeted therapies may be in part mediated by the intestinal RAS and changes in the microbiome. This review summarizes studies on gut microbiota and RAS physiology. Expanding the research on this topic may lay a foundation for new therapeutic paradigms in gastrointestinal diseases and multiple systemic disorders.

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Section: Ras and Gut Microbiota In Health And Diseasementioning

confidence: 88%

Section: Absorption and Digestionmentioning

confidence: 99%

Gut microbiota and renin-angiotensin system: a complex interplay at local and systemic levels

Jaworska

Koper

Ufnal

2021

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Besides, they also play important roles in pathological conditions such as inflammation, oxidation, and fibrosis ( Oliveira et al, 2020 ). Radioimmunoassay showed higher levels of Ang I and Ang II in IBD patients, indicating the protection role of ACE2 in gastrointestinal inflammation ( Jaszewski et al, 1990 ; Garg et al, 2012 ).…”

Section: Ace2: Regulating the Gastrointestinal Inflammationmentioning

confidence: 99%

ACE2 in the Gut: The Center of the 2019-nCoV Infected Pathology

Guo

Wang

Han

et al. 2021

Front. Mol. Biosci.

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The 2019-nCoV is a rapidly contagious pneumonia caused by the recently discovered coronavirus. Although generally the most noticeable symptoms are concentrated in the lungs, the disorders in the gastrointestinal tract are of great importance in the diagnosis of 2019-nCoV. The angiotensin-converting enzyme 2 (ACE2), an important regulator of many physiological functions, including blood pressure and nutrients absorption, is recently identified as a vital entry for 2019-nCoV to enter host cells. In this review, we summarize its functions both physiologically and pathologically. We also elaborate its conflicting roles from the clews of contemporary researches, which may provide significant indications for pharmacological investigations and clinical uses.

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“…Upon entering the cells via ACE2 [25] , SARS-CoV-2 may be triggering the mTOR inhibition [57] that can culminate in the activation of autophagolysosomes and assembly into intestinal cells, causing dysbiosis, intestinal inflammation and diarrhea, as has been shown with the administration of rapamycin [18] , [43] . Moreover, deregulations in the ACE2 pathway and substrates cause a reduction in the tryptophan uptake, a process identified as one of the causes of mTOR inhibition in other studies, which are related to intestinal disorders [16] , [43] , [44] , [45] . Thus, we propose that SARS-CoV-2 causes alteration of the intestinal microbiota, which culminates in a diarrheal process through the ACE2/mTOR/autophagy pathway in enterocytes.…”

Section: Evaluation Of the Hypothesismentioning

confidence: 99%

“…Studies suggest that when ACE2 is downregulated, there is a tryptophan reduction, which causes a decrease in mTOR activation and intestinal dysbiosis, resulting in diarrhea and increased susceptibility to intestinal inflammation from other diseases, such as colitis [16] , [43] . In addition, scientific studies show that other proteins and substrates correlated with ACE2 deregulation, such as depletion of angiotensin 1–7 and neutral amino acid transporter B 0 AT1 deficiency, are correlated with decreased amino acid uptake, such as tryptophan, and gastrointestinal manifestations [43] , [44] , [45] .…”

Section: Evaluation Of the Hypothesismentioning

confidence: 99%

Premises among SARS-CoV-2, dysbiosis and diarrhea: Walking through the ACE2/mTOR/autophagy route

et al. 2020

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Recently, a new coronavirus (SARS-CoV-2) was discovered in China. Due to its high level of contagion, it has already reached most countries, quickly becoming a pandemic. Although the most common symptoms are related to breathing problems, SARS-CoV-2 infections also affect the gastrointestinal tract culminating in inflammation and diarrhea. However, the mechanisms related to these enteric manifestations are still not well understood. Evidence shows that the SARS-CoV-2 binds to the angiotensin-converting enzyme receptor 2 (ACE2) in host cells as a viral invasion mechanism and can infect the lungs and the gut. Other viruses have already been linked to intestinal symptoms through binding to ACE2. In turn, this medical hypothesis article conjectures that the ACE2 downregulation caused by the SARS-CoV-2 internalization could lead to decreased activation of the mechanistic target of mTOR with increased autophagy and lead to intestinal dysbiosis, resulting in diarrhea. Besides that, dysbiosis can directly affect the respiratory system through the lungs. Although there are clues to other viruses that modulate the ACE2/gut/lungs axis, including the participation of autophagy and dysbiosis in the development of gastrointestinal symptoms, there is still no evidence of the ACE2/mTOR/autophagy pathway in SARS-CoV-2 infections. Thus, we propose that the new coronavirus causes a change in the intestinal microbiota, which culminates in a diarrheal process through the ACE2/mTOR/autophagy pathway into enterocytes. Our assumption is supported by premises that unregulated intestinal microbiota increases the susceptibility to other diseases and extra-intestinal manifestations, which can even cause remote damage in lungs. These putative connections lead us to suggest and encourage future studies aiming at assessing the aforementioned hypothesis and regulating dysbiosis caused by SARS-CoV-2 infection, in order to confirm the decrease in lung injuries and the improvement in the prognosis of the disease.

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Genetic deletion of the angiotensin-(1–7) receptor Mas leads to alterations in gut villi length modulating TLR4/PI3K/AKT and produces microbiome dysbiosis

Cited by 22 publications

References 72 publications

Gut microbiota and renin-angiotensin system: a complex interplay at local and systemic levels

Gut microbiota and renin-angiotensin system: a complex interplay at local and systemic levels

ACE2 in the Gut: The Center of the 2019-nCoV Infected Pathology

Premises among SARS-CoV-2, dysbiosis and diarrhea: Walking through the ACE2/mTOR/autophagy route

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