Implementation of a hypocaloric diet supplemented with probiotic cheese containing L. plantarum TENSIA, in a double-blind, randomized pilot study resulted in several beneficial shifts of health markers in overweight and obese subjects. First, the consumption of probiotic cheese was associated with more efficient reduction of BMI compared with ordinary cheese. This effect was correlated with a significant decrease of water content after probiotic cheese consumption, adjusted for sex and age. Among patients who were taking BP-lowering drugs, there was a significant association between L. plantarum TENSIA colonization and both SBP and DBP at the end of the study, as well as the magnitude of the observed changes in each. In both the probiotic and control groups, the reduction of total cholesterol and low-density lipoprotein was observed after the consumption of 50 g of cheese containing 26% fat for 3 weeks. Significant reduction of the plasma triglyceride level was detected only in the probiotic group.
The use of probiotics to reduce the body weight and cholesterol and triglyceride indices of obese patients seems challenging [27, 28]. However, several clinical and experimental studies have shown that probiotic lactobacilli belonging to the genus Firmicutes did not help to reduce BMI [29, 30]. Species differences may be responsible for this finding, yet. For instance, a report indicates that higher BMI is significantly related to homofermentative L. acidophilus in an age- and sex-adjusted population of healthy volunteers (29).
L. plantarum is a heterofermentative lactic acid bacterium that has been found in a large range of environmental niches [31–35]. It has a proven ability to survive gastric and intestinal transit and easily colonizes the human intestinal tract. Functional properties of L. plantarum TENSIA include antimicrobial activity; production of polyamines and nitric oxide; and moderate anti-oxidative ability . Several studies by different investigators have described the beneficial effects of the consumption of the species L. plantarum on human physiology [31, 36, 37].
Although Smith et al. postulated that responsiveness to probiotics may vary among individuals; such differences do not persist when probiotics are consumed for longer than 9 days . In our study even after 3 weeks of consumption, the consumed strain was detectable in only 64% of patients, and there were quite large differences in the numbers of gene copies of strain TENSIA. This range of gene copies may have affected the total counts of lactobacilli, the magnitude of change in BP indices at the end of the study, and the metabolic data tested.
Plausible mechanisms to explain the associations between health indices and dairy intake are still lacking. A Japanese multicenter study of 87 overweight people (BMI of 24.2 kg/m2) who consumed 200 g of fermented milk per day with or without Lactobacillus gasseri SBT2055 for 12 weeks demonstrated a 1.5% reduction in BMI and hip circumference in the intervention group and no reductions in the control group . In the present study, we observed a similar reduction of BMI after just 3 weeks of consuming probiotic cheese accompanied with some other beneficial changes. Similar to the findings of McNulty et al. , we did not observe an increase of the total number of fecal lactobacilli. However, in our study the presence and DNA copy number of TENSIA were associated with BP reduction. The shifts of lactobacilli count after probiotic intervention that influenced the host metabolism might have been detected in upper parts of intestine [29, 40].
In the present pilot study, the reduction of arterial BP was mainly achieved by BP-lowering medications; however, there was a relevant trend toward an association between the lowering of both morning SBP and DBP and TENSIA colonization. The reduction in SBP and DBP after 8 weeks of intervention has been shown in mildly hypertensive subjects using Lactobacillus helveticus or Saccharomyces cerevisiae[41, 42]. During casein degradation by Lactobacillus helveticus, angiotensin I-converting enzyme (ACE) inhibitory peptides were produced that exerted an antihypertensive effect in vivo. ACE is a highly selective ecto-enzyme that is involved in the regulation of peripheral BP . We detected the ACE inhibitory activity of L. plantarum TENSIA in preliminary in vitro studies (unpublished data). In addition, some other lactobacilli, such as Lactobacillus animalis, produce some bioactive fractions from caseins that possess ACE-inhibitory activities .
The mechanisms behind the arterial BP-lowering effect of our study may include vascular relaxation, which is also correlated with the reduction of excess reactive oxygen species in vascular biology [46, 47]. Our strain, L. plantarum TENSIA, has moderate antioxidant activity and is able to decarboxylate ornithine and produce detectable putrescine in urine . Large amounts of endogenous and exogenous polyamines are present in the gut lumen of healthy humans and stimulate DNA, RNA, and protein synthesis [48, 49] and the maturation of large intestinal mucosa [50, 51]. Although a strong association between exposure to increased counts of intestinal lactobacilli and increased urinary putrescine was detected in our patients, the amount of excreted polyamines did not change significantly at the end of the intervention. However, the more pronounced changes of acetylated spermidine in urine were associated with lower changes of DBP when measured in the morning and with lower content of water in the body. The action of polyamines, including their hypotensive effects, appears to depend closely on their serum concentration . In addition, the production of nitric oxide by the TENSIA strain in vitro also hints at the relaxation of blood vessels; this may be the mechanism linking consumption of TENSIA with BP lowering.
A randomized controlled trial has demonstrated the effects of both milk and soy proteins on lowering BP compared with a carbohydrate-rich diet . In the present human trial, the impact of L. plantarum TENSIA on protein catabolism was demonstrated by the increase of urea in blood. Increased serum urea values are usually caused by high protein diets and/or with some starvation. It is possible that higher counts of lactobacilli in patients consuming cheese with L. plantarum Tensia caused the decrease of the pH of gut. This could be accompanied with some increase of protein putrefaction and blood urea content previously described in experimental animals and metabolic surgery [54–56]. However, in our patients the increased urea values were still kept in normal ranges and also no shifts in uric acid were detected relevant for excess of protein catabolism towards health impairment. Moreover, the functionality of kidneys and liver was not altered by the 3 weeks treatment with hypocaloric diet and probiotic cheese. The possibility to prevent water retention and hypertension with the hypocaloric diet supplemented with probiotic cheese seems worth larger clinical and translational studies.
The important findings of this study were that the consumption of a hypocaloric diet supplemented with protein-rich full-fat cheese resulted in the lowering of blood glucose levels by 18% in both study and control groups, while no increase in total cholesterol, low-density lipoprotein, or triglycerides were observed.
Thus, there is good potential for probiotic cheese containing L. plantarum TENSIA to be included in a hypocaloric diet to reduce the symptoms of metabolic syndrome. This finding may broaden the area of non-medication methods that can be employed to achieve optimal arterial BP values and normalization of the BMI, which currently includes healthy nutrition, quitting smoking, and increasing regular physical activity.
In conclusion, the hypocaloric diet supplemented with a probiotic cheese can help reduce BMI, arterial BP, and the risk of metabolic syndrome in obese patients with hypertension.