Probiotics for cardiovascular health -
The gut is known as the "second brain," as it produces many of the same neurotransmitters, chemicals released by nerves needed for communication with other nerves and tissues.
The gut and brain are also connected through a joint partnership called the gut-brain axis that links biochemical signals both to and from the gastrointestinal tract and the central nervous system.
Research suggests there might be a link, but that it travels in one direction — from the gut to the heart — and that keeping your gut healthy can be another means to protect against heart disease. The gut is the primary home to trillions of microbes, collectively known as the human microbiota.
These microbes help with digestion, manufacture certain nutrients, and release substances that have wide-ranging health effects. Stanley Shaw, a cardiologist at Brigham and Women's Hospital.
Since diet plays a significant role in the composition of gut microbiota, what you feed your gut can therefore affect heart health — for better and for worse. Many probiotic strains are being studied for how they may impact heart health.
Probiotics associated with lowered cholesterol include strains belonging to the Bifidobacteria family, as well as certain strains of Lactobacillus plantarum and Lactobacillus acidophilus. Lactobacillus rhamnosus GG is a probiotic strain found in most yogurts that has been linked to reductions in high-sensitivity C-reactive protein, a biomarker used to assess systemic inflammation.
Some foods that are produced through fermentation are a natural source of probiotics. They include yogurt, kefir, and fermented vegetables, all of which can be found in the refrigerated section of your grocery store.
Yogurt and kefir are nutritious choices for a heart healthy diet. Besides probiotics, yogurt, and kefir are both good sources of protein, magnesium and calcium.
Researchers have linked regular yogurt consumption, defined as eating two or more servings of yogurt per week, to a decreased risk of developing CVD. Choose plain, unsweetened yogurts and kefir to limit the intake of added sugars. Probiotic foods should not be heated or used in cooked recipes, since heat kills off the beneficial probiotic bacteria.
Although probiotic-containing foods can be nutritious choices, they may not contain all of the probiotic strains you need. A probiotic supplement can help balance the types of bacteria in your gut and introduce bacterial strains you may be lacking. Probiotics are available in several forms, including capsules, powders, and liquids.
The supplement facts label will inform you what strains a probiotic contains and how many colony forming units CFUs are in each serving of a probiotic. Eating a nutritious diet also helps maintain intestinal bacteria.
Foods with fiber, such as vegetables, beans, and whole grains, provide prebiotics, which are essentially food for probiotics. An RD can help match you with a probiotic that contains strains that will benefit your health needs and make diet recommendations to support both the gut microbiome and heart health.
Probiotics do more than simply support digestion and bowel movements. acidophilus La5 and B. lactis Bb12 Table 1. lactis Bb12 may be a candidate for a therapeutic dietary option to help people with type 2 diabetes manage their LDL-C and TC levels, but more clinical research is needed.
Two randomized, placebo-controlled double-blind synbiotic studies were shown to decrease LDL-C Table 3. The first study was a parallel-armed study in 32 hypercholesterolemic men and women and examined the combination of L. acidophilus CHO plus inulin. acidophilus CHO and 0. The combination of L. acidophilus strains undefined plus fructo-oligosaccharides was examined in 30 normocholesterolemic men in a crossover study.
acidophilus and a 2. Significant reductions in LDL-C 5. No differences in HDL-C or TAG were found. Since the effect of synbiotics on blood lipids can result from probiotics, prebiotics, or both, it is difficult to determine the direct effects of the probiotic used in these studies on LDL-C.
To strengthen the science on probiotics, guidelines for industry on statistical principles for clinical trials have been developed and their use in future studies to examine and confirm the efficacy of probiotics on LDL-C or other health endpoints is strongly encouraged.
As a rule, confirmatory trials are necessary to provide firm evidence of efficacy or safety. In such trials the key hypothesis of interest follows directly from the trial's primary objective, is always predefined, and is the hypothesis that is subsequently tested when the trial is complete.
In a confirmatory trial, it is equally important to estimate with due precision the size of the effects attributable to the treatment of interest and to relate these effects to their clinical significance.
The randomized, controlled, multicenter clinical trials examining L. reuteri NCIMB include a predefined primary endpoint in the protocol as well as sufficient statistical power to detect an expected change in the primary endpoint.
This is in contrast to other published probiotic clinical studies, in which at times it is unclear whether these guidelines were followed and, therefore, whether firm evidence of efficacy is provided. Research in the s indicated differences between germ-free and conventional rats in their ability to metabolize cholesterol.
Germ-free animals, which lack intestinal microflora, were found to have both lower amounts and different compositions of fecal steroids, higher absorption of dietary cholesterol, and greater accumulation of cholesterol, particularly in the liver, indicating a role for intestinal microbes in cholesterol regulation.
However, the exact mechanism s of action of the limited number of probiotic strains that have been clinically shown in humans to significantly decrease LDL-C levels versus placebo is not completely known. Several potential mechanisms whereby probiotics may reduce circulating cholesterol levels have been proposed: 1 binding of cholesterol by the cellular surfaces and membranes of the probiotics; 2 assimilation of cholesterol particles into growing probiotic cells; 3 microbial deconjugation of bile via bile salt hydrolase BSH , resulting in increased fecal excretion of deconjugated bile salts with a compensatory increase in the use of cholesterol to produce new bile acids; 4 short-chain fatty acid production from fermentation of carbohydrate, leading to decreased levels of blood lipids and reduced production of endogenous cholesterol by the liver; and 5 a reduction in cholesterol absorption, perhaps through BSH activity and deconjugation of biliary salts in the small intestine.
Increasing recognition that atherosclerosis involves a chronic inflammatory process has created interest in arterial acute-phase inflammatory biomarkers, such as high-sensitivity C-reactive protein hs-CRP and fibrinogen, as risk factors for CHD. reuteri NCIMB was shown to lower both hs-CRP by 1.
faecium study found a significant increase in fibrinogen by faecium bacteria strains as a possible reason for the increase in fibrinogen in subjects.
The studies using L. lactis Bb12 did not provide data on inflammatory biomarkers. Further, bile acids function as signaling molecules that can activate a variety of nuclear receptors. These bile receptors, mainly expressed in enterohepatic tissues, can affect glucose tolerance, lipid and energy expenditure, and immune function, thus potentially affecting the risk of CVD and metabolic syndrome.
reuteri NCIMB The National Cholesterol Education Programs Adult Treatment Panel recommends dietary alterations, increased exercise, and other lifestyle changes to reduce CHD risk. The combination of plant sterols, viscous fiber, soy protein, and nuts, in addition to a diet low in saturated fat, has been clinically tested in an outpatient metabolic study.
These results demonstrate a significant LDL-C-lowering effect of a TLC diet with multiple dietary targets that is as effective as a low dosage of a first-generation statin drug.
Probiotics can be added to food products such as yogurt and can also be consumed as capsules. Thus, dietary compliance may be improved by the use of probiotics, leading to greater lowering of LDL-C.
The importance of lowering LDL-C in individuals to reduce major vascular events was highlighted in the Cholesterol Treatment Trialists' Collaboration. Moreover, some individuals do not need marked LDL-C reduction or prefer nonpharmacologic alternatives to statin therapy.
reuteri NCIMB can be among the potential options to manage LDL-C; the use of probiotic-containing diets as a complement to statin therapy should be studied further. In addition to a diet low in saturated fat and cholesterol, the consumption of specific probiotics in the right quantities may produce results comparable to the LDL-C-lowering effect of a low-dose statin drug.
In addition to demonstrating health benefits, therapeutic dietary options such as probiotics must be established as safe for human consumption. The probiotic L. reuteri background exposure in foods and as a commensal organism , bioinformatic and in vitro data characterizing the metabolic phenotypes of the strain, and data on strain-specific safety provided by repeat-dose studies in humans.
reuteri is commonly used by the food industry for its fermentation properties and is one of the most widely used microorganisms for the production of sourdough bread.
reuteri in humans. Several regulatory agencies, such as the US Food and Drug Administration FDA , the European Food Safety Authority, and the Therapeutic Goods Administration of Australia, have recognized L.
reuteri for human consumption. reuteri in infant formula has been shown to be safe and well tolerated and to support normal growth. It should not be assumed that conclusions about the safety of a species of microorganism can be applied to all strains of that species.
reuteri NCIMB strain for antimicrobial resistance, production of antimicrobial compounds, the presence of virulence genes in the genome, and production of potentially harmful metabolites. They found no evidence of characteristics that present food safety concerns.
reuteri NCIMB also was shown to be well tolerated in two clinical trials investigating hypercholesterolemic but otherwise healthy subjects.
Adverse effects in the probiotic and placebo groups were similar. The FDA has concluded that a GRAS determination for L. reuteri NCIMB GRN presents no safety questions, as indicated in its letter to the manufacturer.
The probiotic B. lactis Bb12 in combination with Streptococcus thermophilus Th4 has been determined to be GRAS for use in infant formula. While there are some enterococci with a long history of safe use, others can be opportunistic pathogens. faecium among others should not be used as a dietary ingredient because FDA regards all members of a species that contains human pathogens as potentially harmful to human health.
FDA believes there is an absence of consensus regarding valid scientific ways to distinguish between pathogenic and nonpathogenic members of a single species FDA, Probiotics are increasingly being used by consumers and are advocated by many healthcare professionals.
CVD remains a leading cause of death worldwide, and a reduction in LDL-C remains the primary target for intervention. In recent decades, a number of probiotic strains have been evaluated for their ability to reduce LDL-C and other risk factors for CHD.
Probiotics found to lower LDL-C when compared with placebo include L. reuteri NCIMB 8. The ability of L. reuteri NCIMB to lower blood lipids was established in two multicenter clinical trials in which this probiotic was provided to subjects via food or as supplements.
The proposed mechanism of action involves a reduction in cholesterol absorption as a result of deconjugation of bile salts in the small intestine due to BSH activity. reuteri NCIMB has GRAS status, which was obtained through scientific procedures and confirmed by an expert panel on its use as an ingredient in food and beverages.
A meta-analysis of five studies provides support for the ability of E. faecium to lower LDL-C and other blood lipids via its use in fermented dairy products. However, the FDA has raised concern about the use of E. faecium as a food ingredient. Mixed results were obtained by a combination of L.
lactis Bb12, indicating that this mixture has potential, but more research is needed. reuteri NCIMB is a viable candidate to consider in recommendations for future TLC dietary studies and as a potential option for inclusion in TLC dietary recommendations. To strengthen the science on probiotics, guidelines for industry on statistical principles for clinical trials have been developed, and their use in future studies to examine and confirm the efficacy of probiotics on LDL-C or other health endpoints is strongly encouraged.
A roundtable of leading global experts in heart health, probiotics, and nutrition convened once in person to discuss the development of a scientific review paper examining a new role for probiotics in cardiovascular health. Prior to manuscript submission, the author invited members of the roundtable to review the manuscript and provide comments.
Roundtable members were then contacted individually by phone conference to review their comments and address questions by the author. The author expresses his appreciation for the expert comments provided. Expert reviewers were as follows: Richard J. Deckelbaum, MD, CM, FRCPC; Robert R.
The roundtable was supported by Micropharma. The author also expresses his appreciation to Kevin Comerford, PhD, for his assistance in providing background support in the development of this article. The author was provided support for this review by Micropharma, Montreal, Canada.
Any opinions, findings, conclusions, or recommendations expressed here are those of the author. World Health Organization, World Heart Federation, World Stroke Organization.
Global atlas on cardiovascular disease prevention and control. Published Accessed November 14, Heart disease and stroke statistics — update: a report from the American Heart Association. Google Scholar. National Cholesterol Education Program NCEP Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults Adult Treatment Panel III.
Third Report of the National Cholesterol Education Program NCEP Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults Adult Treatment Panel III Final report. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines.
Diet and lifestyle recommendations revision a scientific statement from the American Heart Association Nutrition Committee. World Health Organization.
Prevention of cardiovascular disease: guidelines for assessment and management of cardiovascular risk. Published August 24, Probiotics and their fermented food products are beneficial for health.
J Appl Microbiol. Grundy SM. Promise of low-density lipoprotein-lowering therapy for primary and secondary prevention.
The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. The evidence for dietary prevention and treatment of cardiovascular disease.
J Am Diet Assoc. Health and Nutritonal Properties of Probiotics in Food Including Powder Milk with Live Lactic Acid Bacteria. Geneva : World Health Organization ; de Vrese M Schrezenmeir J.
Probiotics, prebiotics, and synbiotics. Adv Biochem Eng Biotechnol. Sanz Y Santacruz A Gauffin P. Gut microbiota in obesity and metabolic disorders. Proc Nutr Soc. Human gut microbiota and its relationship to health and disease.
Nutr Rev. Guidelines for the Evaluation of Probiotics in Food. Serum lipids in three nomadic tribes of northern Kenya. Am J Clin Nutr. Mann GV Spoerry A. Studies of a surfactant and cholesteremia in the Maasai. Influence of consumption of probiotics on the plasma lipid profile: a meta-analysis of randomised controlled trials.
Nutr Metab Cardiovasc Dis. Agerbaek M Gerdes LU Richelsen B. Hypocholesterolaemic effect of a new fermented milk product in healthy middle-aged men. Eur J Clin Nutr.
Michelle Routhenstein, MS, RD, Probioticss. Probiotics Ptobiotics popular in both supplements and Exercise and blood sugar regulation foods. While most people associate probiotics Deluxe range digestive Probiotids, Exercise and blood sugar regulation health of your Immune-boosting techniques Proniotics connected to whole body wellness. A healthy intestinal environment influences heart health, brain health, and immune system function. Probiotics are live microorganisms, including different types of bacteria and yeast, that are beneficial to your body. Probiotics are added to supplements and some foods to support a healthy bacterial population in your digestive system, which is known as the gut microbiome.Probiotics for cardiovascular health -
The gut is known as the "second brain," as it produces many of the same neurotransmitters, chemicals released by nerves needed for communication with other nerves and tissues. The gut and brain are also connected through a joint partnership called the gut-brain axis that links biochemical signals both to and from the gastrointestinal tract and the central nervous system.
Research suggests there might be a link, but that it travels in one direction — from the gut to the heart — and that keeping your gut healthy can be another means to protect against heart disease. The gut is the primary home to trillions of microbes, collectively known as the human microbiota.
These microbes help with digestion, manufacture certain nutrients, and release substances that have wide-ranging health effects. Stanley Shaw, a cardiologist at Brigham and Women's Hospital. Since diet plays a significant role in the composition of gut microbiota, what you feed your gut can therefore affect heart health — for better and for worse.
Therefore, the fixed-effects model was used. Six RCTs reported HDL-C, TC, and TG data that could be included in the meta-analysis 5 — 7 , 9 — The final result showed that probiotics may increase HDL-C [WMD 1. All four RCTs reported VLDL data that could be included in the meta-analysis 9 , 13 — The heterogeneity among the two studies was low, so the fixed-effects model was used.
Six RCTs reported FPG data that could be included in the meta-analysis 5 — 7 , 9 — Four RCTs reported insulin, HOMA-IR, and QUICKI data that could be included in the meta-analysis 5 — 7 , 9. Therefore, the random-effects model was used. The results of the meta-analysis showed a statistically significant difference between the experimental group and the control group [WMD 0.
Five RCTs reported SBP and DBP data 5 — 7 , 10 , These results indicate low heterogeneity among the five studies, so the fixed-effects model was used.
The analysis of the included literature revealed LPS, hs-CRP, GSH, TAC, and NO data that could be meta-analyzed. There were two articles for LPS 10 , 11 , In addition, three RCTs reported GSH, TAC, and NO data 5 — 7 , and six RCTs reported hs-CRP data that could be meta-analyzed 5 — 7 , 11 , 17 , In conclusion, using the fixed-effects model, it was observed that probiotics could further increase the levels of GSH [SMD 0.
In the meantime, using a fixed-effects model, it was confirmed that probiotics could further increase the levels of NO [WMD 5. Six RCTs reported the hs-CPR data that can be meta-analyzed.
Moludi et al. found that 4. However, Sun et al. did not find evidence that probiotics could increase the probability of adverse events Other literature either did not report any associated adverse events or did not provide documentation regarding them.
CAD, a cardiovascular disease characterized by a chronic inflammatory response and plaque accumulation, has become a major cause of cardiovascular death.
While CAD drugs have shown promising effects in delaying coronary artery lesions, the mortality rate associated with CAD remains high. Therefore, it is crucial to further reduce the risk factors of coronary artery lesions 2.
In recent years, intestinal microorganisms have gained attention in research on coronary artery lesions. The imbalance of intestinal microorganisms is closely linked to the progression of the disease. Intestinal disorders can contribute to the progression of coronary artery lesions Gut microbes have the ability to positively modulate the host immune system, play an immunomodulatory role, defend against pathogenic microbes, and maintain normal physiological functions Studies have indicated that treatment targeting gut microbes can delay the progression of coronary lesions Although there have been meta-analyses on the effects of probiotics on lipid metabolism, glucose metabolism, blood pressure, and inflammatory factors 22 , 23 , they do not consider the effects of conventional drugs on the intestinal flora 24 — Therefore, the objective of this meta-analysis was to examine the effect of probiotics on the risk factors for coronary artery lesions in conjunction with conventional drug therapy for CAD.
Regarding the effect of probiotics on lipid metabolism, although some studies have shown that probiotics can reduce TG and TC concentrations 24 ; this phenomenon was not observed in this meta-analysis. This discrepancy may be attributed to the specific population and conditions included in the analysis.
Most of the existing meta-analyses do not restrict the disease population. In contrast, certain coronary drugs, such as aspirin 27 and atorvastatin 28 , have been found to modulate the intestinal flora, which might diminish the impact of probiotics on the intestinal flora.
Furthermore, the absence of a standardized dietary structure among patients is a crucial factor influencing the outcomes of intestinal flora changes. The included literature did not provide means to achieve dietary uniformity, which could be an important factor influencing the intervention outcomes.
However, such an effect was not observed in patients with CAD alone. In terms of intervention duration, time is another factor that affects the results.
This discrepancy may be related to the cycle of changes in the intestinal flora structure. In addition, probiotics can potentially increase the concentrations of TAC, GSH, and NO, which contribute to cardiovascular dilation and antioxidant capacity Moreover, they can further decrease the levels of LPS, TMAO, and inflammatory response, all of which are beneficial in delaying the progression of coronary artery lesions and improving the prognosis of patients This reversal of intestinal barrier damage further decreases the entry of harmful substances such as LPS and TMAO into the bloodstream This process ultimately sustains a chronic inflammatory response.
TMAO binds to PERK 34 , leading to increased FOXO1 activity and activation of the AKT signaling pathway, resulting in insulin resistance and diabetes. FOXO1 can also affect the farnesol X receptor and small heterodimeric chaperone receptor activation, which downregulates the expression of the Cyp7a1 gene and upregulates the expression of bile acid transporter genes Abcb11 and Slc10a1 These changes contribute to metabolic syndrome in patients.
In addition, PERK can activate AngII, which leads to hypertension However, probiotics reduce the entry of TMAO and LPS into the blood, thereby mitigating the effects of these risk factors.
Studies have shown that GSH is negatively correlated with fasting blood glucose 37 , and individuals with reduced plasma GSH levels have a significantly increased risk of cardiovascular disease The increase in GSH and NO may be associated with a reduction in the metabolic syndrome of the patient The elevated GSH levels can react with various free radicals, such as hydroxyl, hypochlorous, superoxide, and peroxynitrite 40 , 41 , and reduce hydrogen peroxide production, thereby mitigating cellular damage and oxidative stress In addition, NO inhibits leukocyte adhesion to blood vessels and platelet aggregation and adhesion, contributing to the delay of coronary lesion progression 43 Figure 7.
Therefore, this meta-analysis confirmed the effect of probiotics or synbiotics on the risk factors for coronary artery lesions in the treatment setting with conventional medications.
After a rigorous literature screening process, 10 papers with 10 studies were finally included for data consolidation to objectively evaluate the effect of probiotics on coronary artery lesions. This study has some limitations and strengths. The limitations include the following: 1 Since no specific drugs for coronary heart disease were given in the included literature, this may introduce bias to the intervention results.
The small sample size of some outcome indicators reduces the precision of the results. Instead, the risk factors for the prognosis of coronary heart disease were selected for analysis.
Future studies should focus on direct analysis of major cardiovascular adverse events. Future studies should consider a more diverse population. Despite these limitations, the study also has strengths. Different diseases are closely related to the structure of intestinal flora, and most current articles do not separately analyze specific diseases.
This study specifically conducted a meta-analysis of probiotic interventions to minimize the influence of disease on intervention factors. In this study, the control group consisted of patients receiving conventional drugs for coronary heart disease, while the experimental group received conventional drugs for coronary heart disease in combination with probiotic treatment.
The study highlights the additional benefits provided by the addition of probiotics and suggests that future treatment regimens incorporating probiotics may further enhance the prognosis of patients with coronary heart disease.
In summary, the current evidence suggests that probiotics can significantly reduce the risk of coronary artery lesions, and the addition of probiotics to conventional medications for CAD may improve the prognosis of patients with CAD.
However, the aforementioned findings still require further confirmation through large-sample and high-quality RCTs due to the potential impact of probiotic species type, intervention duration, CAD subtype, and sample size. Using probiotics or synbiotics, along with conventional medications for CAD, can further reduce the risk factors for coronary artery lesions and improve the prognosis of patients.
The data sets presented in this study can be found in online repositories. All experiments were conducted at the Scientific Research Center, the Third Affiliated Hospital of Zunyi Medical University The First People's Hospital of Zunyi.
YL and NH conceived and designed the research. ZY and MX reviewed the controversial points of the retrieved documents. ZY guided the design of the article and pointed to the discussion section of the article.
All authors approved the final version of the manuscript and agreed to be accountable for all aspects of the work in ensuring that questions associated with the accuracy or integrity of any part of the work are appropriately investigated and resolved.
All persons designated as authors qualify for authorship, and all those who qualify for authorship are listed. All authors contributed to the article and approved the submitted version. This work was supported by the Guizhou Provincial Health and Health Commission Science and Technology Fund Project gzwkj , the Key Discipline Development Fund of the First People's Hospital of Zunyi, and the Key Discipline Development Fund of Guizhou Province.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.
Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Akhabue E, Thiboutot J, Cheng JW, Vittorio TJ, Christodoulidis G, Grady KM, et al. New and emerging risk factors for coronary heart disease. Am J Med Sci. doi: PubMed Abstract CrossRef Full Text Google Scholar.
Tsao CW, Aday AW, Almarzooq ZI, Alonso A, Beaton AZ, Bittencourt MS, et al. Heart disease and stroke statistics update: A report from the American Heart Association. Anhê FF, Jensen B, Perazza LR, Tchernof A, Schertzer JD, Marette A, et al. Bacterial postbiotics as promising tools to mitigate cardiometabolic diseases.
The first line of treatment is proper nutrition and physical activity [ 1 ]. Probiotic supplements along with prebiotics were found to improve the hyperglycemia state. When multi-strain probiotics along with symbiotic supplements were provided to individuals in a hyperglycemia state as their baseline, there was an improvement in their blood glucose level BGL [ 1 ].
Glucose tolerance and increased satiety with weight loss were found when individuals were administered OFS which lead to Bifidobacterium and endotoxin levels to be normalized. Butyrate, which has properties of propionate that can lower blood glucose, is produced by several bacteria [ 4 ].
Other studies found that with a symbiotic shake of L. acidophilus , Bifidobacterium and L. Though these studies demonstrate that supplementation with probiotics with symbiotic may help in the control of hyperglycemia and T2DM, larger studies are needed to confirm.
The glucose-lowering effect is due to the metabolites of these bacteria which was shown to affect biological signaling pathways, modulated genes involved in ubiquitination and proteasome process, and altered autonomic nerve activity [ 1 ]. It is also vital to note that probiotics or synbiotic alone did not cause a significant reduction in fasting blood glucose levels.
There have not been direct studies that compare the effect of prebiotic intake on cardiovascular health; however, there has been an observation on the serum lipid profiles, which all have an effect on CV [ 2 ]. In order to use probiotics to help lower cholesterol, the probiotics adhesion property to the human intestinal epithelial cells is a critical characteristic that must be considered [ 14 ].
This characteristic is to ensure that there is extended probiotic transit time in the gastrointestinal trace which was found to cause cholesterol-lowering effects in vivo. Studies have shown a lower low-density lipoprotein and total cholesterol, along with increases in high-density lipoprotein cholesterol, a reduction in systolic blood pressure SBP , increases in antioxidant activity, and influences on leptin regulation as a result of probiotics [ 9 ].
This is done through an enzyme called bile salt hydrolase BSH which causes a decrease in the absorption of cholesterol in the blood stream and is an essential criterion for the selection of probacteria [ 9 , 13 ].
This enzyme unconjugated bile acids, which eventually cause a decrease in circulating triglycerides and plasma LDL and VLDL levels [ 12 , 20 ]. The most associated BSH active probiotics are Lactobacillus , Lactococcus, and Bifidobacterium [ 21 ]. These bacteria have been observed to lower cholesterol both in vitro and in vivo [ 28 ].
For example, see [ 14 ], which found that L. fermentum NCIMB and NCIMB were able to lower cholesterol in an in vitro analysis.
They found that L. plantarum ATC had the best results [ 22 ]. Another study found that the BSH candidate L. reuteri NCIMB had the capabilities to lower cholesterol in otherwise healthy individuals [ 12 ].
This is because Lactobacillus species are able to colonize and survive in small intestines [ 21 ]. These studies have demonstrated why lactic acid bacteria with BSH are being classified as having hypocholesterol effect. More specifically, trials that used multiple strains versus single strains and fermented products versus capsule found that multi-strain and fermented methods both caused a decrease in total cholesterol and LDL [ 13 ].
Probiotic soy products in association with cardiovascular risk factors were observed. The fecal microbiota that was used was Lactobacillus spp. Their results showed a negative correlation with Enterococcus spp. with cholesterol, non-HDL cholesterol, and autoantibody against LDL [ 29 ].
However, this study was performed with rabbits, and future studies with human subjects are necessary for a confirmed effect. This study found that there was a positive correlation between Lactobacillus , Bifidobacterium , Enterococcus, and HDL-C levels [ 29 ]. However, in relation to T2DM patients, there were some studies, which found that probiotics failed to maintain a significant effect on lipid profiles [ 7 ].
Prebiotics, however, were found to maintain hypocholesterolemic effects in the T2DM individuals [ 7 ]. Other methods in which probiotics affect blood lipids include binding and incorporating cholesterol to their cell membrane, which decreases the amount of intestinal cholesterol available for absorption, and by producing SCFA which inhibit hydroxymethylglutaryl CoA reductase.
Lactobacillus species have protease-sensitive receptors on their cell surface. These receptors bind to exogenous cholesterol or phosphatidylcholine vessels, which then incorporate cholesterol into their cell membrane. This is strain- and growth-dependent action [ 21 ].
Probiotics, performing the mechanism of a 3-hydroxymethyl-glutaryl-coenzyme A HMG-CoA reductase inhibitor, was shown with dietary fibers prebiotics altering the functionality of gut microbiome including the stimulation of microbial metabolite production such as short-chain fatty acid which impacts cholesterol metabolism.
The lowering of cholesterol with prebiotics is believed to occur through two mechanisms. The first one is it lowers cholesterol absorption by enhancing cholesterol excretion via feces and the second is through the production of SCFAs upon selective fermentation by intestinal bacterial microflora.
Inulin and arabinoxylan, both prebiotics, can alter gut microbiome to stimulate SCFA production which has been already shown to effect cholesterol metabolism [ 12 ]. The mechanism behind this is that cholesterol is removed though the incorporation of cholesterol into cellular membranes in the intestine [ 13 ].
In terms of fermented food, Monascus purpureus rice was found have similar actions as statin and acted as a HMG-CoA reductase inhibitor, decreasing the makeup of cholesterol [ 6 ].
The studies that have conflicting findings could possibly be due to the delivery system. Studies varied whether the probiotics were given in capsule versus fermented foods. However, in a limited number of meta-analysis of studies, it was found that probiotics using fermented foods were more effective in reducing total cholesterol and LDL than in capsule [ 13 ].
Hypertension has several risk factors, such as sedentary lifestyle, lipid and hypercholesterolemia, chronic inflammation, inconsistent modulation of renin-angiotensin system RAS , sodium sensitivity, personal habits, anxiety, and stress. This blood pressure BP -lowering effect through probiotics is due to a decrease in nitrogen oxide production in macrophages, reducing reactive oxygen species and enhancing dietary calcium absorption using different mechanism.
These mechanisms have been found to be related to the production of SCFAs, CLA, GA A, and angiotensin-converting enzyme ACE inhibitor peptides [ 8 ]. Short-chain fatty acids SCFAs , which have a role in both energy metabolism and adipose tissue expansion, also have two sensory receptors that have been linked to BP regulation.
Some of the probiotic strains that were noted to cause a decrease in SBP were L. casei , Streptococcus thermophiles , L. plantarum , and L. helveticus [ 9 ].
Fermented milk products have been shown to have antihypertensive properties in both animal models and clinical trials [ 6 ]. Blood pressure release may also be due to a decrease in blood lipids, body weight, and IR. On continuing, blood pressure is normally controlled with a variety of biochemical pathways, including the RAS system.
The generation of antihypertensive bioactive peptides causes an ACE-inhibitory activity [ 8 ]. Different strains of probiotics have varying potencies as ACE inhibitory activity based on different bioactive peptides [ 18 ].
When prebiotics were used along with probiotics or the probiotic strains were enhanced via fermentation substrates, the proteolytic activity and ACE inhibition were increased [ 20 ].
Fermentation is able to produce bioactive ACE-inhibitory type peptides, casokinins and lactokinins. Probiotics are able to generate these peptides though fermentation having caseinolytic and lactose hydrolyzing enzyme systems [ 9 ]. Consuming probiotic soy milk led to a decrease in BP in a limited number of type II diabetic mellitus subject in a clinical trial lasting 8 weeks [ 15 ].
This study did not find any alterations of anthropometric measures which had been found in other studies. This could be that there are strain-specific properties [ 15 ]. However, subpopulation studies showed no significant difference and there are no definitive recommendations at this time.
Cardio-arterial diseases are often associated with hypercholesterolemia, diabetes, and other metabolic-related diseases. The change in gut microbiota can cause an increase in the level of trimethylamine N-oxide TMAO , which has been linked to an increased risk of major adverse cardiovascular events observed in large clinical cohorts.
However, additional studies are needed to determine the mechanism of CVD through TMAO [ 7 ]. Apo A-V deficient mice were found to have increased precursors of small dense LDL, which is a predictor of coronary artery disease [ 16 ].
This deficiency has been observed with bile salt hydrolase expressing probiotics to have an important role in not only lipid metabolism but also atherosclerosis development.
reuteri NCIMB when provided to non-diabetic subjects with hypertriglyceridemia caused a decrease in apolipoprotein B, which is associated with atherogenic VLDL and LDL products [ 16 ].
It was also shown to reduce CRP and fibrinogen which are two factors of atherogenesis [ 12 ]. However, this study only included small healthy hypercholesterolemia population, and the probiotic was given either in capsule or in yoghurt format. In mice, Lactobacillus species was found to lower arteriosclerosis [ 20 ].
When provided through powered supplement, L. curvatus and L. plantarum caused a significant increase in apo A-V [ 16 ]. With varying methods of providing the probiotics, more controlled studies are necessary to understand the relationship between probiotics and cardio-arterial disease.
Fermented products may provide a decrease in the development of atherosclerosis with the activation of G-protein-coupled bile acid receptor [ 25 ]. In a study that compared atherosclerotic lesions in the aortic vessel in animals treated with fermented soy product supplements versus a control group, the ones that were provided the supplement was found to have a lower percentage of aortic vessel covered with lesions [ 29 ].
Fermented whole grains are also able to lower coronary heart disease [ 6 ]. Heart failure causes a variety of systemic effects on multiple organs. While there are no heart failure changes observed to effect the gut microbial composition, there have been changes that could cause or increase the incidence of heart failures.
New research is currently observing probiotics therapy providing direct cardio-protective effect to the heart. This protection would result in a reduced ischemic injury and improve cardiac function after an infarction [ 20 ].
TMAO, which is effected by gut microbiota, can be linked to both the development and progression of atherosclerosis and cardiovascular disease and is effected by gut microbiota [ 21 ].
However, a majority of studies have only observed the effects in mice. Continuing due to individuals not realizing that they are at risk for infarction, consuming probiotics as prophylaxis is unlikely and the prevalence of heart failure is stagnant.
Patients with chronic kidney disease have an increased risk for cardiovascular disease through having hyperhomocysteinemia, increased lipoprotein, oxidative stress, and inflammation.
Vascular dysfunction in both humans and experimental animals with CKD has been discovered to be due to an increased production and impaired renal excretion of p-cresyl sulfate and indoxyl sulfate which pairs CKD with vascular disease.
These toxins along with others are normally cleared by the kidneys. When kidney patients were provided probiotics, there was a decrease in those toxins. However, due to the uremic environment of the gut that is often associated with CKD, probiotic may become ineffective or less ineffective [ 23 ].
Both composition and function characterize the biodiversity of microbiota [ 4 ]. The gastrointestinal microbiota includes bacteria, archaea, protozoa, fungi, and different viruses, with anaerobic bacteria and the predominant source [ 4 ].
There are even geographic variations that have been found in relation to the type of Lactobacillus , varying from the western and eastern hemispheres. The colon has the largest variety of microorganism and is the focus part of most studies [ 4 ].
Bifidobacterium , Lactobacillus , Propionibacterium , and Bacteroidetes are the dominant species of obligate microflora [ 5 ]. Lactic acid-producing Bifidobacterium and Lactobacillus are often the focal points of studies due to their beneficial effects that is caused by their expression of immunomodulatory and pathogen-antagonistic molecules [ 2 ].
These bacteria produce butyrate, which highlights some properties of propionate and is observed as the preferred metabolic fuel for colonocytes possessing antineoplastic properties.
This contributes to energy production [ 4 ]. Propionate affects colonic muscular contraction, relaxation of resistance vessels, and stimulation of colonic electrolyte transport and insulin resistance [ 4 ].
There are also studies which showed normal microbiota effect on brain metabolism, the immune system, and a couple of homeostatic routes [ 3 ]. Some examples of these changes are an increase in Firmicutes and a decrease in Bacteroidetes [ 18 ]. With recent studies showing gut microbiota related to the pathogenesis of cardiovascular disease, probiotics, which are live microbial food supplements, could balance intestinal microbial resulting in the treatment or prevention of cardiovascular disease [ 9 , 11 ].
The gut environment also plays a role in the type of bacteria found per location in the tract. The tract varies from an alkaline pH in the small bowel to an acidic pH in the stomach [ 31 , 32 ]. It has been discovered that both are lactic acid bacteria which are vital to the gastrointestinal track normal residents.
These two are commonly used in fermented food for the prevention and treatment of different disorders ranging from constipation to high cholesterol levels [ 27 ]. When an individual is healthy, most of the microbiota act symbiotically with the host.
The interaction between the gut epithelial cells and the microbes and the metabolites produced is responsible for the maturation of intestinal epithelial cells, enteric nervous system, intestinal vascular system, and the mucosal immune system.
However, an imbalance in gut bacteria has been shown in numerous studies to be linked to a variety of diseases. In order to reestablish a balance, probiotics, prebiotics, and synbiotics have been used and observed. Probiotics are able to affect the GI tract through their interaction with the intestinal epithelial cells, luminal flora, and mucosal immune cell components of the GI tract [ 28 ].
Antibiotics usage in early life has been determined to deplete some components of microbiota causing disrupted normal gut microbiota development [ 4 ]. Prebiotics such as fructo-oligosaccharides do not support the growth of antibiotic-related pathogens like C. difficile [ 31 ]. difficile -associated diarrhea.
acidophilus , L. rhamnosus GG, L. delbrueckii , and L. fermentum are several bacteria that have been shown to decrease the occurrence of antibiotic-induced diarrhea [ 10 ]. difficile , a main concern with the usage of antibiotics pathogenesis, is the disruption of indigenous intestinal microbiome.
Probiotics were shown in several studies to decrease C. difficile risks; those studies had several limitations such as the type of probiotic variation, the duration of use, and different dosages [ 35 ]. Therefore, C. difficile and probiotic relationship require more in-depth research. There have been a variety of studies that observe and prove the health benefits and clinical effects of probiotics to GI abnormalities such as irritable bowel syndrome, gastric ulcer, and antibiotic-associated diarrhea and some cancers [ 8 ].
Lactobacillus and Bifidobacteria influence on resident microbiota can range from temporarily replacing missing parts or supplementing certain population, or by stimulating some of the resident microbiota. Lactobacillus species, which has been noted in several studies to provide beneficial effects when they are presented, is metabolically active and contains several properties that affect the whole intestinal microbiota biodiversity [ 4 ].
Prebiotics have been shown to suppress indigestion and diarrhea that were caused by pathogens [ 2 ]. Continuing, they can also aid in preventing the growth of harmful competitors, prevent the growth of exogenous microbes, and lower the substrate availability for pathogens [ 19 ].
fermentum ME-3 has been found able to suppress Gram-negative bacteria. Some probiotics have an antagonistic effect such as L. paracasei and L. plantarum with Salmonella microaerobic , L. plantarum against C. difficile colitis anaerobic , L. paracasei against Helicobacter pylori , and B. longum against Shigella sonnei and E.
In an analysis of several studies, probiotics were determined to have a better outcome than non-probiotics therapy for maintenance therapy. However, they did not give benefit in inducing the remission of ulcerative colitis. This could be due to various methods used, different sample sizes, and controlled variables [ 34 ].
Prebiotics can also influence the composition of bacteria in human gut [ 9 ]. Several studies showed that when given supplements of fructan and inulin, there was an increased number of Bifidobacteria [ 19 ].
Other types of prebiotics that have been found to positively affect the gut microbe are arabinoxylan and inulin. These two have a modifying ability through affecting the makeup of and function ability of gut microbe [ 12 ].
Bifidobacteria and Lactobacilli selected fermentation of prebiotics have supported symbiotic gut microbiota through improving numbers of these commensals and decreasing the number of neutral or pathogenic organisms.
Example of acidic fermentation products are lactate and short-chain fatty acid, butyrate acetate, and propionate [ 2 ]. These products can have benefits in the gut, for example, butyrate supports intestinal epithelium, and along with other SCFAs, they have benefits that are distal to the gut system.
The type of probiotics being suggested may differ based on goals and shelf life. World Health Organization WHO suggests that in order to provide health benefits, probiotics must be able to endure human digestion including gastric juices and bile and be capable of multiplying once they arrive in the GI tract [ 9 ].
About 1 in hwalth deaths are Immune-boosting techniques to heart disease, with 1 halth 3 Exercise and blood sugar regulation being preventable [1]. Cardiovacsular statistic healgh alarming for a Exercise and blood sugar regulation that gor be preventable for millions. While some Proviotics are fr predisposed to heart conditions, millions caloric restriction and telomere length advanced cardiovascular Immune-boosting techniques due to a poor diet and sedentary lifestyle. It's no wonder that if what you eat increases the risk of heart disease, then what you put into your gut could have positive effects, too. Studies show that specific probiotic bacteria strains have positive effects on heart health, including lowering cholesterol levels, reducing inflammation, and even supporting a healthy weight [2]. Therefore, using targeted probiotics for heart health supplements could be just the trick to keeping your ticker beating strong. Support cardio wellness all year round with a targeted probiotic for Heart Health.
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