Immunomodulatory effects of probiotic bacteria in healthy adults

Probiooteilla kantakohtaisia vaikutuksia ihmisen immuunijärjestelmään terveillä aikuisilla Probiooteilla on kantakohtaisia tulehduksen välittäjäaineita vähentäviä vaikutuksia ja probioottien yhdistelmien vaikutukset eroavat yksittäisten kantojen vaikutuksista selviää TtM Riina Kekkosen tuoreesta väitöstutkimuksesta. TtM Riina Kekkonen on selvittänyt väitöskirjassaan eri probioottikantojen vaikutuksia immuunivasteeseen valkosolumallissa sekä terveillä aikuisilla lumekontrolloiduissa kliinisissä tutkimuksissa. Aikaisemmin probioottien vaikutuksia on tutkittu lähinnä allergian ja erilaisten vatsavaivojen ehkäisyssä ja hoidossa. Probiootteja sisältäviä tuotteita käyttävät kuluttajat ovat kuitenkin useimmiten terveitä aikuisia, ja probioottien vaikutus terveiden aikuisten immuunijärjestelmään on ollut puutteellisesti selvitettyä. Valkosolumallissa probioottikantojen havaittiin poikkeavan toisistaan niiden kyvyssä aktivoida immuunivasteen välittäjäaineiden, sytokiinien, tuotantoa. Anti-inflammatorisia, eli tulehdusta lievittäviä vaikutuksia nähtiin lähinnä Bifidobacterium ja Propionibacterium sukuihin kuuluvilla kannoilla. Streptococcus ja Leuconostoc sukuihin kuuluvat kannat puolestaan aktivoivat Th1 tyyppistä, soluvälitteistä immuunivastetta. Eri probioottien kombinaatiot eivät saaneet aikaan voimakkaampaa aktivaatiota yksittäisiin kantoihin verrattuna, joka viittaa probioottien keskinäiseen kilpailuun niiden ollessa kontaktissa ihmisen solujen kanssa. Probioottikantojen valinta kliinisiin tutkimuksiin tehtiin niiden anti-inflammatoristen ominaisuuksien perusteella. Parhaita anti-inflammatorisia kantoja olivat B. lactis ssp. animalis Bb12 ja P. freudenreichii ssp. shermanii JS, joiden lisäksi tutkimuksiin valittiin myös L. rhamnosus GG (LGG) hyvin tutkittuna referenssikantana. Solutöiden tulokset eivät olleet täysin verrannollisia kliinisen työn tuloksiin, koska LGG näytti omaavan parhaat anti-inflammatoriset ominaisuudet kliinisissä tutkimuksissa vaikka solutyössä sen aikaansaamat vasteet olivat melko vaimeita. Kolmen viikon kliinisessä tutkimuksessa terveillä aikuisilla LGG alensi mm. tulehdusta kuvaavan C-reaktiivisen proteiinin ja inflammatoristen sytokiinien määrää. Pidemmässä kolmen kuukauden pituisessa kliinisessä tutkimuksessa LGG:llä ei ollut vaikutusta terveiden aikuisten infektiosairastavuuteen, mutta LGG lyhensi vatsavaivojen kestoa. Probioottien vaikutukset immuunijärjestelmään näyttävät olevan kantakohtaisia ja erityisesti Lactobacillus rhamnosus GG:llä havaittiin anti-inflammatorisia vaikutuksia. Valkosolumallia ei tulisi käyttää ainoana probioottikantojen skriinausmenetelmänä niiden immunologisia vaikutuksia selvitettäessä, koska solutöiden tulokset eivät olleet täysin verrannollisia kliinisten tutkimusten tuloksiin. Sen sijaan veren perifeeristen lymfosyyttien eristäminen ja niiden aktivoitumisen selvittäminen lyhytaikaisessa kliinisessä tutkimuksessa voisi toimia suhteellisen helppona skiinausmenetelmänä.Probiotics have strain-specific effects on immune system in healthy adults Probiotics are strain-specifically able to modulate the release and actions of inflammatory mediators in healthy adults. Immunomodulatory effects of probiotic multispecies should be studied as the effects differ from single strains. MSc Riina Kekkonen investigated the immunomodulatory effects of probiotics in a primary cell culture model using human peripheral blood mononuclear cells (PBMC) as well as in healthy adults in randomized, double-blind, placebo-controlled clinical intervention studies in her thesis. Previously, probiotics have been mostly examined in the prevention and treatment of different gastrointestinal diseases and allergies. Probiotic products, however, are usually consumed by the general, healthy population but not much is known on their immunomodulatory effects in healthy adults. Probiotic strains from six different genera showed clear differences in their ability to induce cytokine responses in PBMC in vitro. Strains belonging to the Streptococcus and Leuconostoc genera were the most potent inducers of Th1-type cytokines, whereas strains from the Bifidobacterium and Propionibacterium genera induced anti-inflammatory IL-10 production. No combinations of probiotics resulted in enhanced cytokine production compared with individual strains, suggesting that different bacteria compete with each other during host cell-probiotic interactions. The selection of strains for the clinical trials was made based on their anti-inflammatory potential. The strains possessing the best anti-inflammatory potential, namely B. lactis ssp. animalis Bb12 (Bb12) and P. freudenreichii ssp. shermanii JS (PJS), along with L. rhamnosus GG (LGG) as a well-documented reference probiotic, were thus selected for further clinical studies in healthy adults. The results of the in vitro setting did not entirely reflect the in vivo results as the best anti-inflammatory strain was LGG, which induced only moderate IL-10 production in vitro compared with Bb12 and PJS strains. In the three-week clinical setting in healthy adults, LGG seemed to demonstrate the best anti-inflammatory potential reflected as a small decrease in inflammatory mediators, such as sensitive CRP and inflammatory cytokines like TNF-alfa as well as in the modulation of global serum lipidomics profiles. In the three-month intervention LGG had no effect on the incidence or duration of respiratory infections in healthy adults but it was able to reduce the duration of gastrointestinal symptoms. Probiotics have strain-specific effects on immune system in healthy adults and especially L. rhamnosus GG seemed to posses anti-inflammatory potential. The in vitro screening of cytokine responses in a primary cell culture using human PBMC should not be used as the only indicator of immunomodulatory properties of probiotics, as the in vitro model did not reflect the effects in vivo. Instead, the ex vivo production of cytokines in PBMC after probiotic intervention could offer a relatively easy and quick model for screening of immunomodulatory effects of probiotics. The mechanisms of specific host-probiotic interactions in the gut resulting in systemic and clinical effects warrants further investigations

Running a Marathon Induces Changes in Adipokine Levels and in Markers of Cartilage Degradation - Novel Role for Resistin

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Effects of a fibre-enriched milk drink on insulin and glucose levels in healthy subjects

<p>Abstract</p> <p>Background</p> <p>The glycaemic response to foods is dependent on the quality and content of carbohydrates. Carbohydrates in the form of dietary fibre have favourable effects on insulin and glucose metabolism and may help to control energy intake. Dairy products have a relatively low carbohydrate content, and most of the carbohydrate is in the form of lactose which causes gastrointestinal symptoms in part of the population. In order to avoid these symptoms, dairy products can be replaced with lactose-free dairy products which are on the market in many parts of the world. However, the effects of lactose-free products on insulin and glucose metabolism have not been studied.</p> <p>Methods</p> <p>In the present study, we investigated the effects of 1) a lactose-free milk drink, 2) a novel fibre-enriched, fat- and lactose-free milk drink and 3) normal fat-free milk on serum glucose and insulin levels and satiety using a randomized block design. Following an overnight fast, 26 healthy volunteers ingested 200 ml of one of these drinks on three non-consecutive days. Insulin and glucose levels and subjective satiety ratings were measured before the ingestion of the milk product and 20, 40, 60, 120 and 180 minutes after ingestion. The responses were calculated as the area under the curve subtracted by the baseline value (AUC minus baseline).</p> <p>Results</p> <p>The insulin response was significantly lower for the fibre-enriched milk drink than it was for the other milk products (AUC, <it>P </it>= 0.007). There were no differences in the response for glucose or in the AUC for the subjective satiety ratings between the studied milk products.</p> <p>Conclusion</p> <p>The present results suggest that this novel milk drink could have positive effects on insulin response.</p

Lactobacillus rhamnosus GG Intake Modifies Preschool Children's Intestinal Microbiota, Alleviates Penicillin-Associated Changes, and Reduces Antibiotic Use

Antibiotic use is considered among the most severe causes of disturbance to children's developing intestinal microbiota, and frequently causes adverse gastrointestinal effects ranging from mild and transient diarrhoea to life-threatening infections. Probiotics are commonly advocated to help in preventing antibiotic-associated gastrointestinal symptoms. However, it is currently unknown whether probiotics alleviate the antibiotic-associated changes in children's microbiota. Furthermore, it is not known how long-term probiotic consumption influences the developing microbiota of children. We analysed the influence of long-term Lactobacillus rhamnosus GG intake on preschool children's antibiotic use, and antibiotic-associated gastrointestinal complaints in a double blind, randomized placebo-controlled trial with 231 children aged 2-7. In addition, we analysed the effect of L. rhanmosus GG on the intestinal microbiota in a subset of 88 children. The results show that long-term L. rhamnosus GG supplementation has an influence on the composition of the intestinal microbiota in children, causing an increase in the abundance of Prevotella, Lactococcus, and Ruminococcus, and a decrease in Escherichia. The treatment appeared to prevent some of the changes in the microbiota associated with penicillin use, but not those associated with macrolide use. The treatment, however, did reduce the frequency of gastrointestinal complaints after a macrolide course. Finally, the treatment appeared to prevent certain bacterial infections for up to 3 years after the trial, as indicated by reduced antibiotic use.Peer reviewe

Intestinal microbiome is related to lifetime antibiotic use in Finnish pre-school children

Early-life antibiotic use is associated with increased risk for metabolic and immunological diseases, and mouse studies indicate a causal role of the disrupted microbiome. However, little is known about the impacts of antibiotics on the developing microbiome of children. Here we use phylogenetics, metagenomics and individual antibiotic purchase records to show that macrolide use in 2-7 year-old Finnish children (N = 142; sampled at two time points) is associated with a long-lasting shift in microbiota composition and metabolism. The shift includes depletion of Actinobacteria, increase in Bacteroidetes and Proteobacteria, decrease in bile-salt hydrolase and increase in macrolide resistance. Furthermore, macrolide use in early life is associated with increased risk of asthma and predisposes to antibiotic-associated weight gain. Overweight and asthmatic children have distinct microbiota compositions. Penicillins leave a weaker mark on the microbiota than macrolides. Our results support the idea that, without compromising clinical practice, the impact on the intestinal microbiota should be considered when prescribing antibiotics.Peer reviewe

Intestinal Microbiota in Healthy Adults: Temporal Analysis Reveals Individual and Common Core and Relation to Intestinal Symptoms

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Associations between the human intestinal microbiota, Lactobacillus rhamnosus GG and serum lipids indicated by integrated analysis of high-throughput profiling data

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Faecal Metaproteomic Analysis Reveals a Personalized and Stable Functional Microbiome and Limited Effects of a Probiotic Intervention in Adults

Recent metagenomic studies have demonstrated that the overall functional potential of the intestinal microbiome is rather conserved between healthy individuals. Here we assessed the biological processes undertaken in-vivo by microbes and the host in the intestinal tract by conducting a metaproteome analysis from a total of 48 faecal samples of 16 healthy adults participating in a placebo-controlled probiotic intervention trial. Half of the subjects received placebo and the other half consumed Lactobacillus rhamnosus GG for three weeks (10(10) cfu per day). Faecal samples were collected just before and at the end of the consumption phase as well as after a three-week follow-up period, and were processed for microbial composition and metaproteome analysis. A common core of shared microbial protein functions could be identified in all subjects. Furthermore, we observed marked differences in expressed proteins between subjects that resulted in the definition of a stable and personalized microbiome both at the mass-spectrometry-based proteome level and the functional level based on the KEGG pathway analysis. No significant changes in the metaproteome were attributable to the probiotic intervention. A detailed taxonomic assignment of peptides and comparison to phylogenetic microarray data made it possible to evaluate the activity of the main phyla as well as key species, including Faecalibacterium prausnitzii. Several correlations were identified between human and bacterial proteins. Proteins of the human host accounted for approximately 14% of the identified metaproteome and displayed variations both between and within individuals. The individually different human intestinal proteomes point to personalized host-microbiota interactions. Our findings indicate that analysis of the intestinal metaproteome can complement gene-based analysis and contributes to a thorough understanding of the activities of the microbiome and the relevant pathways in health and disease.Peer reviewe

A Probiotic Mixture Including Galactooligosaccharides Decreases Fecal beta-Glucosidase Activity but Does Not Affect Serum Enterolactone Concentration in Men during a Two-Week Intervention

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