Decreasing the Adverse Effects in Pelvic Radiation Therapy: A Randomized Controlled Trial Evaluating the Use of Probiotics.

Purpose: The aim of this randomized controlled trial was to evaluate the potential benefit from 2 probiotic bacteria of the species Lactiplantibacillus plantarum against radiation therapy-induced comorbidities. Methods and Materials: Women (>18 years of age) scheduled for radiation therapy because of gynecologic cancer were randomly allocated to consume placebo or either low-dose probiotics (1 × 1010 colony-forming unit/capsule twice daily) or high-dose probiotics (5 × 1010 colony-forming unit/capsule twice daily). The intervention started approximately 1 week before the onset of radiation therapy and continued until 2 weeks after completion. During this period the participants were daily filling in a study diary documenting the incidence and severity of symptoms, intake of concomitant medication, and stool consistency. The primary endpoint was the probiotic effect on the mean number of loose stools during radiation therapy. Results: Of the 97 randomized women, 75 provided data for the analysis of the results. The mean number of loose stools (sum of Bristol stool type 6 and 7) was not significantly reduced in the probiotic groups, but there was a significant reduction in the mean number of days with >1 loose stool with 15.04 ± 8.92 days in the placebo and 8.65 ± 5.93 days in the high-dose probiotics group (P = .014). The benefit was even more pronounced in the 2 weeks following the end of radiation therapy (P = .005). Moreover, intake of the probiotics resulted in a reduced severity of the symptoms grinding abdominal pain (P = .041) and defecation urgency (P = .08) and a reduced percentage of days with these symptoms (P = .023 and P = .042, respectively), compared with placebo. There were no differences regarding reported adverse events. Conclusions: Intake of the 2 probiotic bacteria was beneficial and reduced many measures or symptoms of the radiation-induced toxicity in women treated for gynecologic cancer.

Fewer Community-Acquired Colds with Daily Consumption of Lactiplantibacillus plantarum HEAL9 and Lacticaseibacillus paracasei 8700:2. A Randomized, Placebo-Controlled Clinical Trial.

BACKGROUND: Viral infections of the upper airways are the most common cause for absence from work or school, and there is evidence for probiotic efficacy in reducing the incidence and severity of these infections. OBJECTIVES: We aimed to confirm the previously reported beneficial effects of Lactiplantibacillus plantarum HEAL9 and Lacticaseibacillus paracasei 8700:2 against community-acquired common colds and identify a possible mechanism of action. METHODS: In a double-blind study, healthy adults (18-70 years of age) with at least 4 colds during the last 12 months before recruitment were randomly allocated to consume either probiotics (n = 448; total daily dose of 109 CFU with the 2 strains equally represented) or placebo (n = 450) once daily for 12 weeks. Recruitment took place from October to February during 2013-2016 (over 3 cold seasons). The probiotic impact on the severity of the colds (Wisconsin Upper Respiratory Symptom Survey-21) was the primary endpoint, whereas secondary endpoints included the incidence rate and duration of colds and an analysis of immune markers. Mann-Whitney U test and mixed model were used for the analysis of continuous variables and Fisher´s exact test was used for the analysis of categorical endpoints. RESULTS: Symptom severity was not reduced after intake of the probiotic, despite the positive trend seen in the first season. However, significantly fewer colds were experienced in the probiotic group (mean of 1.24 colds) as compared to the placebo group (mean of 1.36 colds; P = 0.044) for subjects reporting at least 1 cold, the incidence of recurring colds was 30% lower (20.8% vs. 29.8%, respectively; P = 0.055), and the use of analgesics was 18% lower (26.3% vs. 32%, respectively; P = 0.07). After 12 weeks, the change from baseline for IFN-γ differed between the groups (mean difference of -7.01; 95% CI, -14.9 to 0.93; P = 0.045). CONCLUSIONS: Intake of Lactiplantibacillus plantarum HEAL9 and Lacticaseibacillus paracasei 8700:2 can be protective against multiple colds in adults prone to getting colds.This trial was registered at clinicaltrials.gov as NCT02013934.

Probiotic fruit beverages with different polyphenol profiles attenuated early insulin response.

BACKGROUND: Consumption of polyphenol-rich fruits and vegetables may improve postprandial glucose and insulin levels and hence promote well-being. Previously it has been observed that consumption of bilberry decreases the postprandial insulin demand. The intention with the present study was to compare the impact of different supplements with various polyphenol profiles, on the postprandial glucose and insulin responses in healthy young adults. METHODS: In a randomized, controlled, crossover study the postprandial glycemic and insulin responses were observed in eleven healthy adults after intake of five different beverages containing bilberry (European blueberry), blackcurrant, beetroot, mango and rose hip, respectively; all drinks were enriched with the same composition of fermented oatmeal and probiotics. The control was a glucose drink. The profile and content of the polyphenols in the different beverages were determined by HPLC-DAD analysis. The antioxidative capacity of the different beverages were measured by TEAC and DPPH assays. RESULTS: Beverages containing bilberry, blackcurrant, mango or rose hip significantly attenuated the early postprandial insulin response (0-90 min), but showed no effect on glucose response. Drinks with bilberry or rose hip reduced the insulin response from the very early phase (0-30 min), and had significantly lower insulin index compared with the control. The efficiency of the bilberry and rose hip to decrease early postprandial insulin responses correlated with higher phenolic contents. CONCLUSIONS: Supplements with bilberry, blackcurrant, mango or rose hip in the tested probiotic and oatmeal enriched beverage attenuated early-phase insulin response, but had no effect on the postprandial glycemic response. The improved ability of bilberry and rose hip to lower the very early phase of insulin response seems to be due to a higher phenolic content. TRIAL REGISTRATION: The study was retrospectively registered at ClinicalTrials.gov with number NCT03159065 .

Efficacy and Safety of Lactobacillus plantarum DSM 9843 (LP299V) in the Prevention of Antibiotic-Associated Gastrointestinal Symptoms in Children-Randomized, Double-Blind, Placebo-Controlled Study.

OBJECTIVES: To determine if Lactobacillus plantarum DSM9843 (LP299V) reduces the frequency of antibiotic-associated loose/watery stools and gastrointestinal symptoms, and can be administered safely to children who are prescribed antibiotics. STUDY DESIGN: We performed a prospective, double-blind, randomized, placebo-controlled, multicenter, parallel-group study in children receiving outpatient antibiotic therapy in primary healthcare settings. The children were given LP299V/placebo during the antibiotic therapy and for 1 week after the end of treatment. The primary outcome measure was the incidence of at least 1 loose/watery stool (type 6 or 7 according to the Bristol Stool Form Scale). Gastrointestinal symptoms (abdominal pain, abdominal distention, vomiting, and flatulence) were followed up until 1 week after the last intake of the study product. RESULTS: A total of 438 children (male: 235, female: 203) aged 1-11 years (mean ± SD: 5.2 ± 2.7) were randomized to receive LP299V (N = 218) or placebo (N = 220). The incidence of loose/watery stools in the 2 study groups (LP299V and placebo) was similar, 39% vs 44.5% respectively (P = .26) as was the mean number of loose/watery stools (3.9 ± 3.5 vs 4.7 ± 6.3; P = .9). Antibiotic-associated diarrhea (defined as ≥3 loose/watery stools/24 hours starting from 2 hours after initiation of antibiotic treatment until the end of the study) occurred in 2.8% of the subjects receiving LP299V compared with 4.1% in the placebo arm (P = .4). The number of children with abdominal symptoms did not differ between the groups. CONCLUSIONS: No beneficial effect of LP299V compared with placebo was observed for the incidence of loose/watery stools, mean number of loose/watery stools, or the incidence of abdominal symptoms. LP299V had a satisfactory safety profile. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01940913.

Antihypertensive activity of blueberries fermented by Lactobacillus plantarum DSM 15313 and effects on the gut microbiota in healthy rats.

BACKGROUND & AIMS: The aim of the present animal study was to examine the anti-hypertensive capacity of two probiotic products combining blueberries and the tannase producing probiotic bacteria Lactobacillus plantarum DSM 15313 and to investigate if such an effect is linked to a change in the gut microbiota. METHODS: Male Sprague Dawley rats were randomly divided into six groups of nine each. Three groups of the animals were treated with N(G)-nitro-L-arginine methyl ester (L-NAME) in the drinking water (40 mg/L) to induce a hypertensive state, and the other three groups were not treated with L-NAME (healthy rats). Two blueberry products differing in their phenolic acid content were tested and each rat received 2 g/day of the fermented blueberry powders for 4 weeks. The effects of the study products on the blood pressure, blood lipids, inflammatory markers, organ weights as well as caecal microbiota of the healthy (non-L-NAME-treated) rats were analyzed. RESULTS: After four weeks, healthy rats consuming freeze dried fermented blueberries with probiotics had a significant reduction in blood pressure compared to the control rats. In rats with L-NAME induced hypertension there was a significant reduction of the blood pressure after two weeks treatment. The probiotic product with a higher content of phenolic acids reduced ALAT in the healthy rats. Furthermore, ingestion of the probiotic blueberry products resulted in changes of the gut microbiota in the healthy rats. CONCLUSIONS: Blueberries fermented with the tannase producing bacteria L. plantarum DSM 15313 have anti-hypertensive properties and may reduce the risk for cardiovascular diseases.

Intake of Blueberry Fermented by Lactobacillus plantarum Affects the Gut Microbiota of L-NAME Treated Rats.

Prebiotics, probiotics, or synbiotics can be used as means to regulate the microbiota to exert preventative or beneficial effects to the host. However, not much is known about the effect of the gut microbiota on hypertension which is a major risk factor of cardiovascular disease and also a symptom of the metabolic syndrome. The N(G)-nitro-L-arginine methyl ester (L-NAME) induced hypertensive rats were used in order to test the effect of a synbiotic dietary supplement of Lactobacillus plantarum HEAL19 either together with fermented blueberry or with three phenolic compounds synthesized during fermentation. The experimental diets did not lower the blood pressure after 4 weeks. However, the fermented blueberries together with live L. plantarum showed protective effect on liver cells indicated by suppressed increase of serum alanine aminotransferase (ALAT) levels. The diversity of the caecal microbiota was neither affected by L-NAME nor the experimental diets. However, inhibition of the nitric oxide synthesis by L-NAME exerted a selection pressure that led to a shift in the bacterial composition. The mixture of fermented blueberries with the bacterial strain altered the caecal microbiota in different direction compared to L-NAME, while the three phenolic compounds together with the bacteria eliminated the selection pressure from the L-NAME.

Nontypeable Haemophilus influenzae activates human eosinophils through beta-glucan receptors.

Eosinophils are a characteristic component of the inflammatory response seen in several diseases, including allergic asthma and chronic obstructive pulmonary disease. After activation, eosinophil-derived products may exert proinflammatory effects and cause considerable tissue damage. In the present study, we investigated innate interactions between the respiratory tract pathogen nontypeable Haemophilus influenzae (NTHi) and human eosinophils. Bacterial binding to eosinophils was dependent on (1-3)-beta-D-glucan receptors, as deduced from blocking experiments using the soluble glucan derivatives laminarin and scleroglucan. In addition, expression of the beta-glucan receptor dectin-1 was shown in eosinophils by reverse transcriptase-polymerase chain reaction. Activation of the beta-glucan receptors by bacteria elicited a time- and dose-dependent respiratory burst in eosinophils. NTHi caused increased expression of the proinflammatory chemokine interleukin-8 as measured by reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay. Incubation of eosinophils in the presence of NTHi for 4.5 h revealed upregulation of 245 different genes as detected by microarray. Signal transduction-related transcripts were most strongly upregulated, followed by cytokine mRNAs. Our findings suggest that NTHi can induce an innate inflammatory response in eosinophils that is mainly mediated via beta-glucan receptors. This points to possible pathophysiologic mechanisms involving innate recognition of NTHi by eosinophils during infection of the airways, thus promoting inflammation in chronic pulmonary disease.

Comparison of the antibacterial activities of ampicillin, ciprofloxacin, clarithromycin, telithromycin and quinupristin/dalfopristin against intracellular non-typeable Haemophilus influenzae.

Non-typeable Haemophilus influenzae, which is a cause of disease in the upper and lower respiratory tract, can survive intracellularly in human epithelial cells and macrophages. We studied the in vitro activity of five antibiotics against intracellular non-typeable H. influenzae in human type II alveolar epithelial cells. The eukaryotic cells were loaded with bacteria, and extracellular bacteria were killed by gentamicin. After the cells were washed, antibiotics were added at concentrations of 0.12-64 mg/L for 18 h before the numbers of viable intracellular bacteria were determined. Of the antibiotics tested, ciprofloxacin and quinupristin/dalfopristin were the most potent agents, followed by clarithromycin and telithromycin. Ampicillin was not active against intracellularly localized, non-typeable H. influenzae.