Probiotics as Regulators of Lipid Metabolism?
The Heart-Health Benefits of Lactobacillus reuteri NCIMB 30242 By Dr Carrie Decker ND
It seems we cannot discuss any health-related topic nowadays without considering the health of the gut and the microbiota within it. Considerable data show the bacteria in our gut impact our mood and response to stress,, the function of our immune system, and even our metabolic health and the conditions associated with it., Intestinal permeability and a state of dysbiosis in the gut have been shown to contribute not only to a systemic inflammatory state, but also to downstream liver problems such as cholestasis and nonalcoholic fatty liver disease.,, Considering that the liver aids not only in detoxification but also in cholesterol and glucose processing, microbiota-associated endotoxaemia may impact blood sugar regulation and cholesterol balance further downstream as well.,
Our systemic health, too, is influenced by the activity of the gut microbiota. The microbes in our gut have their own metabolic processes, which are vital to their function. Byproducts of these processes include vitamins such as folate, riboflavin, and vitamins K and B12, as well as short-chain fatty acids (SCFAs), which are absorbed into our blood stream and cells, and support our metabolic needs.
Cholesterol metabolism is also affected by the microorganisms in our gut. Cholesterol enters the digestive tract via the diet and biliary secretions, with a combined total average of approximately 1.5 g/day. Bile acids, synthesised in the liver from cholesterol, break the cholesterol down to micelles, and portions of those micelles are absorbed in the duodenum and proximal jejunum., Bile acids are reabsorbed or deconjugated, the latter being done primarily by the enzyme bile salt hydrolase (BSH), which is produced by certain lactobacilli or bifidobacteria in the gut.,,
Deconjugation causes the bile acids to become hydrophobic, further reducing cholesterol absorption. The deconjugated bile acids also become ligands of farnesoid X receptor (FXR), which is highly expressed in the liver and the gut and serves to regulate cholesterol synthesis, uptake, and outflow. Eventually, about 50% of the total cholesterol that enters the digestive tract (from exogenous and endogenous sources) leaves the body through the feces.
Lactobacillus reuteri NCIMB 30242
BSH-producing probiotics have been clinically shown to lower total and low-density lipoprotein cholesterol (LDL-C). Lactobacillus reuteri NCIMB 30242 is one probiotic strain that has been shown to produce this enzyme.
The first clinical study with NCIMB 30242 was a randomised, double-blind, placebo-controlled trial (RDBPCT) with the probiotic as a yogurt formulation, provided to 114 hypercholesterolemic adult men and women not taking a statin or other cholesterol-lowering medications or supplements.22 After taking the yogurt with NCIMB 30242 twice daily for six weeks (a dosage of between 1.9 to 50 billion colony-forming units [CFUs] per yogurt), significant reductions in LDL-C (8.92%), total cholesterol (4.81%), and non-high-density lipoprotein cholesterol (non-HDL-C) (6.01%) were seen compared to placebo, as well as an absolute reduction of 0.19 mmol/L in apolipoprotein B (apoB-100), a predictor of coronary heart disease.
Because data from the first study suggested the time to reach maximum effect may be longer than six weeks, a nine-week follow-up RDBPCT was performed using an encapsulated form of the probiotic. In this study, NCIMB 30242 was provided twice daily, with a potency of between 2.0 billion CFUs (endpoint) and 2.9 billion CFUs (baseline).
One-hundred twenty-seven hypercholesterolemic adults, including those maintained on a stable dose of statin medications but excluding those on alternate cholesterol-reducing medications or supplements, completed this RDBPCT. At the study endpoint, significant reductions in LDL-C (11.64%), total cholesterol (9.14%), non-HDL-C (11.30%), and apoB-100 (8.41%) were seen compared to placebo.24 Significant reductions in fibrinogen (14.25%) and high-sensitivity C-reactive protein (1.05 mg/L) were also noted, indicating NCIMB 30242 may additionally reduce procoagulation tendencies and inflammation. This study, as well as a small pilot study with NCIMB 30242, showed a significant increase in plasma deconjugated bile acid levels along with a reduction in plasma non-cholesterol sterol levels, suggesting the effects are at least in part due to altered bile acid metabolism and reduced cholesterol absorption.
Gastrointestinal (GI) effects.
The impact of NCIMB 30242 on gastrointestinal symptoms has also been investigated clinically. In conjunction with the second cholesterol-focused RDBPCT,24 gastrointestinal symptoms were surveyed with a 93-question self-diagnosis questionnaire for irritable bowel syndrome (IBS) in the 127 hypercholesteremic adults. Much like any population, gastrointestinal symptoms of diarrhea, constipation, bloating, and burning were not uncommon, with over half of the population in the placebo group and the intervention being found to have functional bowel disorders at baseline.
After taking NCIMB 30242 or placebo twice daily for nine weeks, those receiving the intervention were found to have significant improvements in their scores related to overall GI health status and diarrhea symptoms compared to placebo. Additionally, a significantly greater percentage of responders having improved gastrointestinal health status and less diarrhea was seen in the probiotic group.
Vitamin D metabolism.
Questions concerning the effect of NCIMB 30242 on vitamin D have also been addressed. With NCIMB 30242’s effects on cholesterol absorption, concerns were raised that it may reduce levels of this fat-soluble vitamin, which, when low, is a risk factor for cardiovascular disease.
Along with assessment of the gastrointestinal and cholesterol effects in the nine-week RDBPCT discussed previously,24,26 serum levels and dietary intake of vitamin A, vitamin E, beta-carotene, and 25-hydroxyvitamin D (25[OH]D) were evaluated post hoc. Again, much like the standard population, levels of 25(OH)D were found to be borderline in many of the individuals in this study, with a mean of 30 ng/mL and 27.2 ng/mL in the placebo and intervention groups, respectively. Rather than finding a decrease in serum 25(OH)D, an increase of it by 25.5% (14.9 nmol/L) was seen in the NCIMB 30242 group, a significant mean change of 22.4% (17.1 nmol/L) as compared to placebo. No significant differences were observed in the levels of vitamins A, E, or beta-carotene between the baseline and final values between or within groups.
Comprehensive labs were performed to evaluate the safety of NCIMB 30242, including assessment of a complete blood count, comprehensive metabolic panel, and serum lipase level. No biochemical changes raising concern for the safety of the intervention were seen,22, and the frequency and intensity of adverse events were similar to placebo, with no serious events occurring.
In a population where hypercholesterolemia, functional digestive symptoms, and borderline low vitamin D status are prevalent, NCIMB 30242 seems to offer comprehensive support for these common issues.
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