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Int J Clin Exp Physiol. 2023;10(3):1-2.
https://www.ijcep.org Letter to Editor
International Journal of Clinical and Experimental Physiology, Vol 10, Issue 3, Jul-Sep, 2023 1
DOI: ["DOI"].11.2.1
Copyright Information :
Copyright Author (s) 2023 Distributed under
Creative Commons CC-BY 4.0
Publishing Partner : EManuscript Tech. [www.emanuscript.in]
Efficacy and Challenges in Usage of Gut Microbiome in
Management of Hypertension
Balaji Pishey Ashwathnarayan rao1
, Smitha Ranoji rao Varne2
1
Consultant Physician and ESH Hypertension Specialist, Sakaria hospital, Affiliated to RGUHS (Rajiv Gandhi University of Health Sciences)
Bangalore, Karnataka, INDIA.
2
Consultant Naturopathy and Yoga, Integrative Medicine, and Nutritionist, Preksha Wellness and Yoga Center, Sakaria Hospital, Affiliated to
RGUHS (Rajiv Gandhi University of Health Sciences), Bangalore, Karnataka, INDIA.
Sir,
Hypertension is a major risk factor for cardiovascular and
cerebrovascular diseases and leads to target organ damage
including myocardial infarction, stroke, heart failure, and
renal disease. Around 1.5 billion people worldwide have
hypertension, and it is estimated that it causes about 8 million
deaths per year. Although there are several drugs available
to lower Blood Pressure (BP), a large proportion of treated
patients do not reach the BP targets recommended by current
guidelines.[1]
Non-pharmacological interventions to prevent and
treat hypertension are lifestyle modifications, such as increased
physical activity, yoga/pranayama, reduced salt and alcohol
intake, quitting smoking, weight loss, and a healthy diet with
high fiber content. Additionally, gut microbiome, which is quite
diverse, also has potential influence on blood pressure.[1,2]
Gut microbiome are commercially available as probiotic
supplements, which are defined as “live microorganisms that,
when administered in adequate amounts, confer a health
benefit on the host”. Probiotics are known to have potential role
in different diseases. For example, probiotic administration is
useful in acute infective diarrhea, irritable bowel syndrome,
causes reduction of cholesterol levels, attenuates hypertension,
myocardial hypertrophy, and heart failure after myocardial
infarction.[2,3]
Certain metabolites of gut microbiome like Short Chain Fatty
Acids (SCFAs), bile acids, Hydrogen Sulphide (H2
S) can decrease
blood pressure by dilating peripheral blood vessels, maintaining
vascular endothelial function, improving insulin sensitivity,
lowering blood lipids, reducing inflammatory response,
decreasing heart rate, inhibiting the sympathetic nervous
system, and protecting kidney function, while other metabolites
Trimethyl Amine-Oxide (TMAO), Lipopolysacharides (LPS) can
increase blood pressure by constricting blood vessels, increasing
inflammatory response, damaging vascular endothelial function,
and exacerbating atherosclerosis.[2-4]
Foods rich in fibers like fruits, vegetables, and grains,
promote growth of SCFA-producing gut microbiota including
Bifidobacterium lactis, lactobacillus rhamnosus, lactobacillus
casei, lactobacillus helveticus, lactobacillus paracasei,
Coprococcus, Butyrivibrio, and Anaerobutyricum soehngenii
specieshavedemonstratedmodestbloodpressureloweringeffects
in humans. On the other hand, foods rich in red meat, promotes
growth of gut microbiota like Anaerococcus hydrogenalis,
Clostridium asparagiformis, Clostridium hathewayi, Clostridium
sporogenes, Desulfovibrio desulfuricans, and Escherichia
fergusoni, which convert choline, phosphatidylcholine, lecithin,
and L-carnitine, into Trimethyl Amine (TMA) and TMAO.
TMAO acts as a risk factor for the development of hypertension
by affecting renin-angiotensin system. High salt intake also has
shown increased plasma concentration of TMAO, due to gut
dysbiosis in rats.[2-5]
In animal studies, beef feeding increased the relative abundance
of Firmicutes, while decreasing Bacteroidetes. Increased
Firmicutes/Bacteroidetes ratio, is often associated with increased
BMI (body mass index) in human subjects and increased BMI is
positively associated with increased blood pressure.[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.[7]
The
effects of gut microbiota on BP, whether beneficial or harmful,
are influenced by multiple factors including genetics, epigenetics,
lifestyle choices, microbiome strain or species, and antibiotic
usage. Probiotics available as supplements often contain mixed
cultures of live microorganisms rather than single strains. With
International Journal of Clinical and Experimental Physiology, Vol 10, Issue 3, Jul-Sep, 2023
2
Rao and Varne: Probiotics and Hypertension
the increase of age, baseline Body Mass Index (BMI), treatment
duration, and systolic BP, the effects of probiotics on BP are still
unknown. All these factors collectively contribute to overall
control of blood pressure.[3,4]
Even though there is plethora of scientific literature available
regarding the role of gut microbiome in hypertension, but till date,
there is neither clarity nor established guidelines and consensus
regarding strain-specificity for hypertension in any of the existing
national and international guidelines like European Society of
Hypertension (ESH), International Society of Hypertension
(ISH) etc. Innovative microbiome-based or targeted medication
related research, which have the potential to revolutionize the
treatment of hypertension are highly recommended in future
because effects of probiotics can be specific to certain probiotic
species and strains. Recommendations for their use in the clinical
practice or in research studies need to be compulsorily species and
strain specific and interpretation of data from studies involving
mixture of probiotic supplements can be misleading in terms of
beneficial effects, efficacy and safety and should be cautious.
ABBREVIATIONS
BP: Blood Pressure; SCFA: Short Chain Fatty Acids; H2S:
Hydrogen Sulphide; TMAO: Trimethyl Amine- Oxide; LPS:
Lipopolysacharides; TMA: Trimethyl Amine.
CONFLICT OF INTEREST
The authors declare that they have no conflict of interest.
REFERENCES
1. Balaji PA, Smitha RV. Integrated review of management of hypertension by lifestyle
changes, yoga, exercise, acupressure, plant/herbal and allopathic medications, and
newer interventions. Indian J Integr Med. 2023; 3: 1-8.
2. Sun D, Xiang H, Yan J, He L. Intestinal microbiota: A promising therapeutic target for
hypertension. Front Cardiovasc Med. 2022; 9: 970036. doi: 10.3389/fcvm.2022.9700
36, PMID 36457803.
3. Shreiner AB, Kao JY, Young VB. The gut microbiome in health and in disease. Curr
Opin Gastroenterol. 2015; 31(1): 69-75. doi: 10.1097/MOG.0000000000000139, PMID
25394236.
4. Yang Z, Wang Q, Liu Y, Wang L, Ge Z, Li Z, et al. Gut microbiota and hypertension:
association, mechanisms and treatment. Clin Exp Hypertens. 2023; 45(1): 2195135.
doi: 10.1080/10641963.2023.2195135, PMID 36994745.
5. Albracht-Schulte K, Islam T, Johnson P, Moustaid-Moussa N. Systematic review of
beef protein effects on gut microbiota: implications for health. Adv Nutr. 2021; 12(1):
102-14. doi: 10.1093/advances/nmaa085, PMID 32761179.
6. Mei X, Mell B, Aryal S, Manandhar I, Tummala R, Zubcevic J, et al. Genetically
engineered Lactobacillus paracasei rescues colonic angiotensin converting enzyme
Cite this article: Rao BPA. Efficacy and Challenges in Usage of Gut Microbiome in Management of Hypertension. Int J Clin Exp Physiol.
2023;10(3):40-4.
*Correspondence:
Dr. Balaji Pishey Ashwathnarayan rao
Dr. B R Ambedkar Medical College,
Affiliated to RGUHS (Rajiv Gandhi
University of Health Sciences) Bangalore,
Karnataka, INDIA.
Email: drpaba@rediffmail.com, drpaba2@
gmail.com,
ORCID iD: 0009-0003-3230-8990

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

  • 1. Int J Clin Exp Physiol. 2023;10(3):1-2. https://www.ijcep.org Letter to Editor International Journal of Clinical and Experimental Physiology, Vol 10, Issue 3, Jul-Sep, 2023 1 DOI: ["DOI"].11.2.1 Copyright Information : Copyright Author (s) 2023 Distributed under Creative Commons CC-BY 4.0 Publishing Partner : EManuscript Tech. [www.emanuscript.in] Efficacy and Challenges in Usage of Gut Microbiome in Management of Hypertension Balaji Pishey Ashwathnarayan rao1 , Smitha Ranoji rao Varne2 1 Consultant Physician and ESH Hypertension Specialist, Sakaria hospital, Affiliated to RGUHS (Rajiv Gandhi University of Health Sciences) Bangalore, Karnataka, INDIA. 2 Consultant Naturopathy and Yoga, Integrative Medicine, and Nutritionist, Preksha Wellness and Yoga Center, Sakaria Hospital, Affiliated to RGUHS (Rajiv Gandhi University of Health Sciences), Bangalore, Karnataka, INDIA. Sir, Hypertension is a major risk factor for cardiovascular and cerebrovascular diseases and leads to target organ damage including myocardial infarction, stroke, heart failure, and renal disease. Around 1.5 billion people worldwide have hypertension, and it is estimated that it causes about 8 million deaths per year. Although there are several drugs available to lower Blood Pressure (BP), a large proportion of treated patients do not reach the BP targets recommended by current guidelines.[1] Non-pharmacological interventions to prevent and treat hypertension are lifestyle modifications, such as increased physical activity, yoga/pranayama, reduced salt and alcohol intake, quitting smoking, weight loss, and a healthy diet with high fiber content. Additionally, gut microbiome, which is quite diverse, also has potential influence on blood pressure.[1,2] Gut microbiome are commercially available as probiotic supplements, which are defined as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host”. Probiotics are known to have potential role in different diseases. For example, probiotic administration is useful in acute infective diarrhea, irritable bowel syndrome, causes reduction of cholesterol levels, attenuates hypertension, myocardial hypertrophy, and heart failure after myocardial infarction.[2,3] Certain metabolites of gut microbiome like Short Chain Fatty Acids (SCFAs), bile acids, Hydrogen Sulphide (H2 S) can decrease blood pressure by dilating peripheral blood vessels, maintaining vascular endothelial function, improving insulin sensitivity, lowering blood lipids, reducing inflammatory response, decreasing heart rate, inhibiting the sympathetic nervous system, and protecting kidney function, while other metabolites Trimethyl Amine-Oxide (TMAO), Lipopolysacharides (LPS) can increase blood pressure by constricting blood vessels, increasing inflammatory response, damaging vascular endothelial function, and exacerbating atherosclerosis.[2-4] Foods rich in fibers like fruits, vegetables, and grains, promote growth of SCFA-producing gut microbiota including Bifidobacterium lactis, lactobacillus rhamnosus, lactobacillus casei, lactobacillus helveticus, lactobacillus paracasei, Coprococcus, Butyrivibrio, and Anaerobutyricum soehngenii specieshavedemonstratedmodestbloodpressureloweringeffects in humans. On the other hand, foods rich in red meat, promotes growth of gut microbiota like Anaerococcus hydrogenalis, Clostridium asparagiformis, Clostridium hathewayi, Clostridium sporogenes, Desulfovibrio desulfuricans, and Escherichia fergusoni, which convert choline, phosphatidylcholine, lecithin, and L-carnitine, into Trimethyl Amine (TMA) and TMAO. TMAO acts as a risk factor for the development of hypertension by affecting renin-angiotensin system. High salt intake also has shown increased plasma concentration of TMAO, due to gut dysbiosis in rats.[2-5] In animal studies, beef feeding increased the relative abundance of Firmicutes, while decreasing Bacteroidetes. Increased Firmicutes/Bacteroidetes ratio, is often associated with increased BMI (body mass index) in human subjects and increased BMI is positively associated with increased blood pressure.[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.[7] The effects of gut microbiota on BP, whether beneficial or harmful, are influenced by multiple factors including genetics, epigenetics, lifestyle choices, microbiome strain or species, and antibiotic usage. Probiotics available as supplements often contain mixed cultures of live microorganisms rather than single strains. With
  • 2. International Journal of Clinical and Experimental Physiology, Vol 10, Issue 3, Jul-Sep, 2023 2 Rao and Varne: Probiotics and Hypertension the increase of age, baseline Body Mass Index (BMI), treatment duration, and systolic BP, the effects of probiotics on BP are still unknown. All these factors collectively contribute to overall control of blood pressure.[3,4] Even though there is plethora of scientific literature available regarding the role of gut microbiome in hypertension, but till date, there is neither clarity nor established guidelines and consensus regarding strain-specificity for hypertension in any of the existing national and international guidelines like European Society of Hypertension (ESH), International Society of Hypertension (ISH) etc. Innovative microbiome-based or targeted medication related research, which have the potential to revolutionize the treatment of hypertension are highly recommended in future because effects of probiotics can be specific to certain probiotic species and strains. Recommendations for their use in the clinical practice or in research studies need to be compulsorily species and strain specific and interpretation of data from studies involving mixture of probiotic supplements can be misleading in terms of beneficial effects, efficacy and safety and should be cautious. ABBREVIATIONS BP: Blood Pressure; SCFA: Short Chain Fatty Acids; H2S: Hydrogen Sulphide; TMAO: Trimethyl Amine- Oxide; LPS: Lipopolysacharides; TMA: Trimethyl Amine. CONFLICT OF INTEREST The authors declare that they have no conflict of interest. REFERENCES 1. Balaji PA, Smitha RV. Integrated review of management of hypertension by lifestyle changes, yoga, exercise, acupressure, plant/herbal and allopathic medications, and newer interventions. Indian J Integr Med. 2023; 3: 1-8. 2. Sun D, Xiang H, Yan J, He L. Intestinal microbiota: A promising therapeutic target for hypertension. Front Cardiovasc Med. 2022; 9: 970036. doi: 10.3389/fcvm.2022.9700 36, PMID 36457803. 3. Shreiner AB, Kao JY, Young VB. The gut microbiome in health and in disease. Curr Opin Gastroenterol. 2015; 31(1): 69-75. doi: 10.1097/MOG.0000000000000139, PMID 25394236. 4. Yang Z, Wang Q, Liu Y, Wang L, Ge Z, Li Z, et al. Gut microbiota and hypertension: association, mechanisms and treatment. Clin Exp Hypertens. 2023; 45(1): 2195135. doi: 10.1080/10641963.2023.2195135, PMID 36994745. 5. Albracht-Schulte K, Islam T, Johnson P, Moustaid-Moussa N. Systematic review of beef protein effects on gut microbiota: implications for health. Adv Nutr. 2021; 12(1): 102-14. doi: 10.1093/advances/nmaa085, PMID 32761179. 6. Mei X, Mell B, Aryal S, Manandhar I, Tummala R, Zubcevic J, et al. Genetically engineered Lactobacillus paracasei rescues colonic angiotensin converting enzyme Cite this article: Rao BPA. Efficacy and Challenges in Usage of Gut Microbiome in Management of Hypertension. Int J Clin Exp Physiol. 2023;10(3):40-4. *Correspondence: Dr. Balaji Pishey Ashwathnarayan rao Dr. B R Ambedkar Medical College, Affiliated to RGUHS (Rajiv Gandhi University of Health Sciences) Bangalore, Karnataka, INDIA. Email: drpaba@rediffmail.com, drpaba2@ gmail.com, ORCID iD: 0009-0003-3230-8990