APOE Genotypes, Lipid Profiles, and Associated Clinical Markers in a Finnish Population with Cardiovascular Disease Risk Factors.

INTRODUCTION: The APOE ε4 allele predisposes to high cholesterol and increases the risk for lifestyle-related diseases such as Alzheimer's disease and cardiovascular diseases (CVDs). The aim of this study was to analyse interrelationships of APOE genotypes with lipid metabolism and lifestyle factors in middle-aged Finns among whom the CVD risk factors are common. METHODS: Participants (n = 211) were analysed for APOE ε genotypes, physiological parameters, and health- and diet-related plasma markers. Lifestyle choices were determined by a questionnaire. RESULTS: APOE genotypes ε3/ε4 and ε4/ε4 (ε4 group) represented 34.1% of the participants. Genotype ε3/ε3 (ε3 group) frequency was 54.5%. Carriers of ε2 (ε2 group; ε2/ε2, ε2/ε3 and ε2/ε4) represented 11.4%; 1.9% were of the genotype ε2/ε4. LDL and total cholesterol levels were lower (p < 0.05) in the ε2 carriers than in the ε3 or ε4 groups, while the ε3 and ε4 groups did not differ. Proportions of plasma saturated fatty acids (SFAs) were higher (p < 0.01), and omega-6 fatty acids lower (p = 0.01) in the ε2 carriers compared with the ε4 group. The ε2 carriers had a higher (p < 0.05) percentage of 22:4n-6 and 22:5n-6 and a lower (p < 0.05) percentage of 24:5n-3 and 24:6n-3 than individuals without the ε2 allele. CONCLUSIONS: The plasma fatty-acid profiles in the ε2 group were characterized by higher SFA and lower omega-6 fatty-acid proportions. Their lower cholesterol values indicated a lower risk for CVD compared with the ε4 group. A novel finding was that the ε2 carriers had different proportions of 22:4n-6, 22:5n-6, 24:5n-3, and 24:6n-3 than individuals without the ε2 allele. The significance of the differences in fatty-acid composition remains to be studied.

APOE Genotype Disclosure and Lifestyle Advice in a Randomized Intervention Study with Finnish Participants.

BACKGROUND: The APOE ε4 allele is associated with higher risks of cardiovascular diseases and Alzheimer disease than ε3 and ε2. OBJECTIVES: We studied the effectiveness of dietary and lifestyle guidance and personal genetic risk information [ε4 carrier (ε4+); ε4 noncarrier (ε4-)] as motivators for a healthier lifestyle. METHODS: A total of 188 healthy Finnish volunteers (82.4% women; mean ± SD age: 51.0 ± 5.6 y; BMI: 26.0 ± 3.6 kg/m2; total cholesterol: 5.2 ± 0.9 mmol/L) participated in our randomized intervention study. The participants were genotyped for APOE and divided into intervention (INT; INTε4+, n = 33; INTε4-, n = 57) and control groups (CTRL; CTRLε4+, n = 36; CTRLε4-, n = 62). Blood samples, measured observations, and questionnaire data were obtained at baseline and at 1 and 1.5 y. INT participants received their ε4 carrier status at baseline. Monthly Internet-based guidance based on the Finnish Dietary guidelines was provided for all. RESULTS: The proportion of SFAs in plasma over time fluctuated less in INTε4+ than in the other groups (P-interaction < 0.05; primary outcome). The lifestyle guidance increased vegetable consumption from 3.5 to 3.6 portions/d, improved the dietary fat quality score by 5.3%, increased the plasma n-3 (ω-3) FA proportion by 7.3%, and decreased the consumption of high-fat/high-sugar foods from 7.3 to 6.5 portions/wk and total- and LDL-cholesterol concentrations by 4.3% and 6.1%, respectively, in the entire participant population (P < 0.05; secondary outcome). Compared with the ε4- participants, ε4+ participants had 2.4% higher plasma n-6 (ω-6) FA, lower C-peptide (3.9 compared with 4.2 nmol/L × h) and sensitive C-reactive protein values, and decreased plasma malondialdehyde concentrations over time (P < 0.05; secondary outcome). CONCLUSIONS: Lifestyle guidance given to healthy Finnish participants yielded small but beneficial changes. The INTε4+ group did not seem markedly more responsive to the guidance than the other groups.This trial was registered at clinicaltrials.gov as NCT03794141.

A Long-Term Follow-Up Study on Disclosing Genetic Risk Information (APOE) to Promote Healthy Lifestyles in Finland.

AIM: This observational follow-up study was designed to assess the long-term behavioural and clinical effects of receiving personal genetic risk information. The information disclosed was the carrier status of the apolipoprotein E (APOE)alleles, which differentially contribute to the genetic risk for cardiovascular disease (CVD) and Alzheimer's disease. METHODS: This study forms a continuum with a previous 1-year intervention (2010-2011) monitoring the effects of disclosing the carrier status of the APOE ε4risk allele. The follow-up measurements, performed 5.5 years post-intervention, included clinical measurements (blood values and anthropomorphic parameters) and questionnaires (psychological and behavioural factors). The participants were healthy adult volunteers, aged 26-73 years (n = 70) who had participated in the previous intervention, and received their APOE allele status either at the beginning (former test group) or the end of the intervention (former control group). RESULTS: Personal genetic risk information resulted in a moderate health-conscious change in diet and had a slight positive long-term effect on clinical factors, particularly the serum lipids. These improvements were subsequent to the disclosure of genetic information and occurred mainly in the APOE ε4-positive members of the former control group, that is, those who were at increased genetic risk for CVD but had not been informed of their status before the end of the intervention. In contrast, changes in the values and health behaviour of the APOE ε4-positive individuals in the former test group, who had already changed their health behaviour during the previous intervention as a result of being informed of their carrier status, varied more: some continued to improve, some remained at their previously improved level, and some relapsed slightly. Both groups had nonetheless displayed an improvement immediately subsequent to the disclosure of their personal genetic risk. CONCLUSION: Receiving information on increased personal genetic risk (carrier status of APOE ε4)for CVD provided the motivation for improvements in health behaviour. The resulting changes, while modest, in most cases remained visible even after a number of years.

Persistence of probiotic strains in the gastrointestinal tract when administered as capsules, yoghurt, or cheese.

Most clinical studies of probiotics use freeze-dried, powdered bacteria or bacteria packed in capsules. However, probiotics are commercially available in various food matrices, which may affect their persistence in the gastrointestinal tract. The objective of the study was to compare oral and faecal recovery during and after administration of a combination of Lactobacillus rhamnosus GG and LC705, Propionibacterium freudenreichii subsp. shermanii JS, and Bifidobacterium animalis subsp. lactis Bb12 as capsules, yoghurt, or cheese. This randomized, parallel-group, open-label trial (n=36) included a 4-week run-in, 2-week intervention, and 3-week follow-up period. Participants consumed 10(10)cfu/day of probiotic combination and provided saliva and faecal samples before, during, and after the intervention. Strain-specific real-time PCR was used to quantify the strains. L. rhamnosus GG was the only probiotic strain regularly recovered in saliva samples. During the intervention period it was recovered in the saliva of 88% of the volunteers at least once. No difference was found between the yoghurt and cheese groups. At the end of the intervention, L. rhamnosus GG and LC705 counts were high in faecal samples of all product groups (8.08 and 8.67log(10) genome copies/g, respectively). There was no matrix effect on strain quantity in faeces or the recovery time after ceasing the intervention. For P. freudenreichii subsp. shermanii JS and B. animalis subsp. lactis Bb12, a matrix effect was found at the end of the intervention (P<0.01 and P<0.001, respectively) and in the recovery time during follow-up (P<0.05 for both). Yoghurt yielded the highest faecal quantity of JS and Bb12 strains (8.01 and 9.89log(10) genome copies/g, respectively). The results showed that the administration matrix did not influence the faecal quantity of lactobacilli, but affected faecal counts of propionibacteria and bifidobacteria that were lower when consumed in cheese. Thus, the consumption of probiotics in yoghurt matrix is highly suitable for studying potential health benefits and capsules provide a comparable means of administration when the viability of the strain in the capsule product is confirmed.

Comparative genomic analysis of Lactobacillus rhamnosus GG reveals pili containing a human- mucus binding protein.

To unravel the biological function of the widely used probiotic bacterium Lactobacillus rhamnosus GG, we compared its 3.0-Mbp genome sequence with the similarly sized genome of L. rhamnosus LC705, an adjunct starter culture exhibiting reduced binding to mucus. Both genomes demonstrated high sequence identity and synteny. However, for both strains, genomic islands, 5 in GG and 4 in LC705, punctuated the colinearity. A significant number of strain-specific genes were predicted in these islands (80 in GG and 72 in LC705). The GG-specific islands included genes coding for bacteriophage components, sugar metabolism and transport, and exopolysaccharide biosynthesis. One island only found in L. rhamnosus GG contained genes for 3 secreted LPXTG-like pilins (spaCBA) and a pilin-dedicated sortase. Using anti-SpaC antibodies, the physical presence of cell wall-bound pili was confirmed by immunoblotting. Immunogold electron microscopy showed that the SpaC pilin is located at the pilus tip but also sporadically throughout the structure. Moreover, the adherence of strain GG to human intestinal mucus was blocked by SpaC antiserum and abolished in a mutant carrying an inactivated spaC gene. Similarly, binding to mucus was demonstrated for the purified SpaC protein. We conclude that the presence of SpaC is essential for the mucus interaction of L. rhamnosus GG and likely explains its ability to persist in the human intestinal tract longer than LC705 during an intervention trial. The presence of mucus-binding pili on the surface of a nonpathogenic Gram-positive bacterial strain reveals a previously undescribed mechanism for the interaction of selected probiotic lactobacilli with host tissues.

Probiotic intervention has strain-specific anti-inflammatory effects in healthy adults.

AIM: To evaluate the effects of three potentially anti-inflammatory probiotic bacteria from three different genera on immune variables in healthy adults in a clinical setting based on previous in vitro characterization of cytokine responses. METHODS: A total of 62 volunteers participated in this randomized, double-blind and placebo-controlled parallel group intervention study. The volunteers were randomized to receive a milk-based drink containing either Lactobacillus rhamnosus GG (LGG), Bifidobacterium animalis ssp. lactis Bb12 (Bb12), or Propionibacterium freudenreichii ssp. shermanii JS (PJS) or a placebo drink for 3 wk. Venous blood and saliva samples were taken at baseline and on d 1, 7 and 21. Fecal samples were collected at baseline and at the end of intervention. RESULTS: The serum hsCRP expressed as the median AUC(0-21) (minus baseline) was 0.018 mg/L in the placebo group, -0.240 mg/L in the LGG group, 0.090 mg/L in the Bb12 group and -0.085 mg/L in the PJS group (P = 0.014). In vitro production of TNF-alpha from in vitro cultured peripheral blood mononuclear cells (PBMC) was significantly lower in subjects receiving LGG vs placebo. IL-2 production from PBMC in the Bb12 group was significantly lower compared with the other groups. CONCLUSION: In conclusion, probiotic bacteria have strain-specific anti-inflammatory effects in healthy adults.

Prevention of sports injuries: systematic review of randomized controlled trials.

Increased participation in sports has led to more sports injuries. Evidence-based methods to prevent sports injuries are needed. A systematic review was conducted of the effects of randomized controlled interventions to prevent sports injuries. A systematic search was performed of various databases and the reference lists of articles and reviews. Two reviewers independently extracted the data and assessed the methodological quality of the included trials. Thirty-two trials (24,931 participants) met the inclusion criteria. We found evidence of the preventive effect of 3 types of injury prevention interventions. In 5 trials including 6 different comparisons (2446 participants), custom-made or prefabricated insoles reduced lower limb injuries compared with no insoles in military recruits (risk reduction > or =50% in 4 comparisons). All 7 studies investigating external joint supports (10,300 participants) showed a tendency to prevent ankle, wrist, or knee injuries (risk reduction > or =50% in 5 studies). All 6 multi-intervention training programs (2809 participants) were effective in preventing sports injuries (risk reduction > or =50% in 5 studies). Various interventions may prevent sports injuries. A decreased risk of sports injuries was associated with the use of insoles, external joint supports, and multi-intervention training programs. More high-quality randomized controlled trials in different sports and populations are needed.

Effect of humic material on the bacterioplankton community composition in boreal lakes and mesocosms.

The bacterioplankton community composition in two Finnish forest lakes with different content of humic substances was studied by denaturing gradient gel electrophoresis (DGGE) and sequencing of the major bands. The same dominant bacterial phylotypes were detected in the bacterioplankton communities of clear-water Lake Ahvenlammi and humic Lake Sammalisto. For 4 years, in every water layer, Actinobacteria was the dominant and Verrucomicrobia the second most common phylum. In the hypolimnion, other dominant phyla were also found. We set up a mesocosm experiment to assess the effect of a sudden load of allochthonous humus extract to the bacterioplankton community composition. Changes in the bacterial communities were followed in four control and four humus extract-added mesocosms for 50 days. In the humic mesocosms the phylotypes of allochthonous Proteobacteria arriving with the humus extract were initially prevalent but disappeared during the first weeks. After this the Actinobacteria-dominated communities resembled the bacterioplankton communities of the control mesocosms and Lake Ahvenlammi. Towards the end of the experiment the community patterns in all the mesocosms started to change slightly because of erratic occurrence of new proteobacterial phylotypes. Thus the effects of a sudden load of allochthonous humic material and bacteria to the bacterioplankton community composition were transient.