Efekti upotrebe probiotika na mikroRNK povezane sa gojaznošću

Obesity is considered to be a chronic complex disease that increases the risk of diabetes, heart diseases and certain cancers. According to the literature, in obese people the gastrointestinal microbiota is disturbed, which could be the cause of the onset of obesity and related diseases. Moreover, there are small non-coding RNAs (microRNAs) that are disturbed in obesity, which are also considered to be a possible mechanism of probiotics’ action. Certain microRNAs are involved in the development and metabolism of adipose tissue cells, as well as the secretion and action of insulin, showing that changed expression of certain miRNAs could have a significant impact on the onset and development of obesity and obesity-related diseases. Thus, miRNAs are considered to be possible markers for the diagnosis and prognosis of various metabolic diseases, and possible therapeutic targets for the treatment of obesity and related diseases. Considering the growing need of the healthcare system for nutraceuticals and dietary supplements that present effective and safe medical nutritive therapy in obese individuals, this work aimed to assess the beneficial effects of probiotics on obesity-related microRNAs. In this review, we described the role of microRNAs and probiotics in obesity and the association between probiotics and obesity- related microRNAs. Circulating miRNAs’ profile in obese individuals significantly differs from that of normal-weight individuals. miRNAs such as miR-155, miR-221, miR-24-3p, and miR- 181a are over-expressed, while miR-26b and 125a are under-expressed in obese patients compared to non-obese individuals. It has been found that supplementation with Bifidobacterium bifidum and Lactobacillus acidophilus could downregulate the expression of miR-155 and miR- 221, and upregulate the expression of miR-26b. Supplementation with a probiotic formulation containing S. boulardii, L. plantarum 299v, and octacosanol led to the downregulation of miR- 155 and miR-24-3p expression. miR-125a and miR-181a were upregulated and downregulated, respectively, after the intervention with L. delbrueckii and L. rhamnosus. After reviewing the available literature, we can conclude that probiotics have beneficial effects on microRNAs altered in obesity, which could provide an effective strategy for the management of obesity.Gojaznost se smatra hroničnom, kompleksnom bolešću koja povećava rizik od nastanka drugih oboljenja poput dijabetesa, kardiovaskularnih oboljenja i određenih karcinoma. Prema literaturnim podacima, kod gojaznih osoba dolazi do narušavanja gastrointestinalne mikrobiote, što nadalje može biti uzrok razvoja gojaznosti i bolesti povezanih sa gojaznošću. Dodatno, postoje male nekodirajuće RNK (mikroRNK) čije su koncentracije promenjene kod gojaznih osoba u poređenju sa osobama normalne telesne mase. Takođe, mikroRNK se smatraju mogućim mehanizmom delovanja probiotika. Određene mikroRNK se smatraju ključnim u procesima razvoja i metabolizma masnog tkiva, kao i u procesima sinteze i delovanja hormona insulina, time ukazujući na to da bi promene u ekspresiji određenih miRNK mogle imati značajan uticaj na nastanak i razvoj gojaznosti i bolesti povezanih sa gojaznošću. Zbog navedenog, miRNK se smatraju mogućim markerima za dijagnozu i praćenje metaboličkih bolesti, ali se razmatraju i kao moguća terapija u tretmanu gojaznosti i oboljenja povezanih sa gojaznošću. U svetlu rastućih potreba sistema zdravstvene zaštite u pogledu dodataka ishrani i nutraceutika koji pružaju efikasnu i bezbednu podršku medicinskoj nutritivnoj terapiji kod gojaznosti, cilj ovog rada bio je da se istraže korisni efekti probiotika na mikroRNK povezane sa gojaznošću. U ovom narativnom pregledu opisali smo ulogu probiotika i mikroRNK u gojaznosti, kao i moguću povezanost probiotika sa mikroRNK koje su izmenjene kod gojaznih ljudi. Profil cirkulišućih miRNK se značajno razlikuje kod gojaznih osoba u poređenju sa osobama normalne telesne mase. Ekspresija miRNK poput miR-155, miR-221, miR-24-3p i miR-181a je značajno povišena, dok je ekspresija miR-26b i miR-125a snižena kod gojaznih osoba u poređenju sa osobama normalne telesne mase. Suplementacija sa Bifidobacterium bifidum i Lactobacillus acidophilus probiotskim sojevima snižava ekspresiju miR-155 i miR-221, dok je ekspresija miR-26b povišena nakon suplementacije ovim sojevima. Probiotska formulacija koja sadrži kombinaciju S. boulardii, L. plantarum 299v i oktakozanola dovela je do smanjenja ekspresije miR-155 i miR-24-3p. Ekspresija miR-125a je bila povećana, dok je ekspresija miR-181a bila snižena nakon suplementacije sojevima L. delbrueckii and L. rhamnosus. Nakon pregleda dostupne literature, možemo zaključiti da probiotici imaju pozitivno dejstvo na mikroRNK izmenjene kod gojaznih osoba, te da bi primena probiotika mogla biti efikasna strategija u tretmanu gojaznosti

Health Benefit Characterization of Dominant Lactobacilli in Traditional Doogh

The aim of our study was the characterization and evaluation of isolated lactic acid bacteria(LAB

Changes in Human Fecal Microbiota Due to Chemotherapy Analyzed by TaqMan-PCR, 454 Sequencing and PCR-DGGE Fingerprinting

BACKGROUND: We investigated whether chemotherapy with the presence or absence of antibiotics against different kinds of cancer changed the gastrointestinal microbiota. METHODOLOGY/PRINCIPAL FINDINGS: Feces of 17 ambulant patients receiving chemotherapy with or without concomitant antibiotics were analyzed before and after the chemotherapy cycle at four time points in comparison to 17 gender-, age- and lifestyle-matched healthy controls. We targeted 16S rRNA genes of all bacteria, Bacteroides, bifidobacteria, Clostridium cluster IV and XIVa as well as C. difficile with TaqMan qPCR, denaturing gradient gel electrophoresis (DGGE) fingerprinting and high-throughput sequencing. After a significant drop in the abundance of microbiota (p = 0.037) following a single treatment the microbiota recovered within a few days. The chemotherapeutical treatment marginally affected the Bacteroides while the Clostridium cluster IV and XIVa were significantly more sensitive to chemotherapy and antibiotic treatment. DGGE fingerprinting showed decreased diversity of Clostridium cluster IV and XIVa in response to chemotherapy with cluster IV diversity being particularly affected by antibiotics. The occurrence of C. difficile in three out of seventeen subjects was accompanied by a decrease in the genera Bifidobacterium, Lactobacillus, Veillonella and Faecalibacterium prausnitzii. Enterococcus faecium increased following chemotherapy. CONCLUSIONS/SIGNIFICANCE: Despite high individual variations, these results suggest that the observed changes in the human gut microbiota may favor colonization with C. difficile and Enterococcus faecium. Perturbed microbiota may be a target for specific mitigation with safe pre- and probiotics

Arbeidsaktivering og sosialt medborgerskap - en litteraturstudie

Målet med denne oppgaven er å diskutere arbeidsaktivering i lys av sosialt medborgerskap. Casen jeg skal studere er Kvalifiseringsprogrammet fra 2007, et arbeidsrettet aktiveringsprogram for sosialhjelpsmottakere. Med påstand om nye rettigheter, økt inkludering og deltakelse i samfunnslivet, tok programmets intensjoner sosialhjelpsmottakernes medborgerskap på alvor. Jeg ønsker å kritisk vurdere om data matcher intensjonene. Oppgavens problemstilling er Hvordan kan Kvalifiseringsprogrammet fungere som en mulighet for, eller en barriere mot sosialt medborgerskap? Jeg har gjennomført en litteraturstudie basert på publisert forskning, og forskningen er innhentet ved hjelp av systematiske søk i utvalgte databaser, i tillegg til snøball-metoden. Jeg har brukt to typer forskningsdata i oppgaven: kvalitative forskningsartikler og evaluerings- og effektstudier. Artiklene er tematisk analysert, fra studiene har jeg dratt ut funn som jeg har vurdert relevante for problemstillingen. Funnene fra forskningen peker på det jeg omtaler som fire spenningsfelt i Kvalifiseringsprogrammet. Første spenningsfelt, «Treffsikkerhet eller fløteskumming», sikter til de skjønnsbaserte inngangsvilkårene, og hvilken betydning disse har for rekrutteringspraksisen. Videre omhandler både «Rimelig eller urimelig» og «Demokratisering eller styring», utformingen av Kvalifiseringsprogrammet som en velferdskontrakt. Disse diskuterer rimeligheten av deltakelse i arbeidsaktivering for en gruppe med mange hindringer mot arbeid, og hvordan programmets kontraktpreg kan gi rom for demokratisering av utforming, brukermedvirkning og myndiggjøring av deltakerne. Siste spenningsfelt, «Verdighet eller skam», diskuterer deltakernes subjektive opplevelser med programmet., hvorvidt denne gir en økt eller svekket følelse av anerkjennelse og verdighet. Kvalifiseringsprogrammet representerer nye muligheter, rettigheter og verdighet, men i mindre grad for sosialhjelpsmottakerne enn det som var tenkt. Programmet har gått fra å ha intensjoner om politisk handlekraft og inkludering, til å bli en arbeidsorientert tvangstrøye hvor evnen til arbeid er den mest avgjørende markøren for det sosiale medborgerskapet

Comprehensive Approach to Distinguish Patients with Solid Tumors from Healthy Controls by Combining Androgen Receptor Mutation p.H875Y with Cell-Free DNA Methylation and Circulating miRNAs

Liquid biopsy-based tests emerge progressively as an important tool for cancer diagnostics and management. Currently, researchers focus on a single biomarker type and one tumor entity. This study aimed to create a multi-analyte liquid biopsy test for the simultaneous detection of several solid cancers. For this purpose, we analyzed cell-free DNA (cfDNA) mutations and methylation, as well as circulating miRNAs (miRNAs) in plasma samples from 97 patients with cancer (20 bladder, 9 brain, 30 breast, 28 colorectal, 29 lung, 19 ovarian, 12 pancreas, 27 prostate, 23 stomach) and 15 healthy controls via real-time qPCR. Androgen receptor p.H875Y mutation (AR) was detected for the first time in bladder, lung, stomach, ovarian, brain, and pancreas cancer, all together in 51.3% of all cancer samples and in none of the healthy controls. A discriminant function model, comprising cfDNA mutations (COSM10758, COSM18561), cfDNA methylation markers (MLH1, MDR1, GATA5, SFN) and miRNAs (miR-17-5p, miR-20a-5p, miR-21-5p, miR-26a-5p, miR-27a-3p, miR-29c-3p, miR-92a-3p, miR-101-3p, miR-133a-3p, miR-148b-3p, miR-155-5p, miR-195-5p) could further classify healthy and tumor samples with 95.4% accuracy, 97.9% sensitivity, 80% specificity. This multi-analyte liquid biopsy-based test may help improve the simultaneous detection of several cancer types and underlines the importance of combining genetic and epigenetic biomarkers

Nutraceutical Approaches of Autophagy and Neuroinflammation in Alzheimer’s Disease: A Systematic Review

Aging and the emergence of age-associated illnesses are one of the major challenges of our present society. Alzheimer’s disease (AD) is closely associated with aging and is defined by increasing memory loss and severe dementia. Currently, there are no therapy options available that halt AD progression. This work investigates three hallmarks of the disease (autophagy, neuroinflammation, and senescence) and systematically analyzes if there is a beneficial effect from three substances derived from food sources, the so called “nutraceuticals” epigallocatechin gallate, fisetin, and spermidine, on these hallmarks. The results imply a positive outlook for the reviewed substances to qualify as a novel treatment option for AD. A combination of nutraceutical substances and other preventive measures could have significant clinical impact in a multi-layered therapy approach to counter AD

Lifestyle-Driven Variations in Nutrimiromic MicroRNA Expression Patterns across and beyond Genders

The importance of diet and lifestyle in maintaining overall health has long been recognised. MicroRNAs (miRNAs) have emerged as key players in the intricate interplay between health and disease. This study, including 305 participants, examined the role of miRNAs from capillary blood as indicators of individual physiological characteristics, diet, and lifestyle influences. Key findings include specific miRNAs associated with inflammatory processes and dietary patterns. Notably, miR-155 was associated with subjects with metabolic diseases and upregulated in age. Additionally, the study revealed diet-related miRNA expressions: high consumption of vegetables, fruits, and whole grains correlated with increased levels of miR-let-7a and miR-328, both implicated in anti-inflammatory pathways, and decreased expression of pro-inflammatory miR-21. In the context of smoking, we found a significant decrease in miRNA-142, known for its downregulation in lung cancer. We observed a sex-biased expression of various miRNAs with significant upregulation of miR-151a in females and a higher expression of miR-155 in ageing females, representing a possible mechanism for the increased susceptibility to autoimmune diseases. In conclusion, the study underscores the significant influence of lifestyle, nutrition, and sex on miRNA profiles. Circulating miRNAs demonstrate significant potential as biomarkers in personalized medicine, highlighting their utility in tailoring healthcare to individual needs

Epigallocatechin Gallate Effectively Affects Senescence and Anti-SASP via SIRT3 in 3T3-L1 Preadipocytes in Comparison with Other Bioactive Substances

Aim. We investigated different bioactive compounds including epigallocatechin gallate (EGCG), anthocyanidin, resveratrol, phloretin, spermidine, butyrate, and β-hydroxybutyrate with regard to their effect on SIRT3 via NRF2 and modulation of the proinflammatory senescence-associated secretory phenotype (SASP) in senescence induced 3T3-L1 preadipocytes. Methods. For induction of senescence, 3T3-L1 preadipocytes were incubated with bromodeoxyuridine (BrdU) for 8 days. Cell cycle inhibition was observed, and β-galactosidase activity was measured. After BrdU treatment, cells were treated with different bioactive compounds in various concentrations for 96 h. ELISA was used for determining proinflammatory cytokine IL6 in SASP cells. Results. CDKN1a increased significantly after BrdU incubation compared to untreated control (p<0.01). All secondary plant ingredients used for treatment, but not anthocyanidin 50 μM, decrease CDKN1a expression (p<0.05), whereas most endogenous substances did not attenuate CDKN1a. IL6 secretion positively correlated with CDKN1a (p<0.01), whereas EGCG could diminish both, IL6 and CDKN1a with the strongest effect (p<0.01). Although NRF2 positively correlated with SIRT3 activation (p<0.05), only resveratrol (p<0.01) and anthocyanidin (p<0.05) could activate NRF2 significantly. Solely anthocyanidin 50 μM (p<0.05) and 100 μM (p<0.01) and EGCG 50 μM (p<0.01) could increase SIRT3 expression. Activation of SIRT3 with EGCG correlated with lowered IL6 secretion significantly (p<0.05) but not with anthocyanidin. Conclusion. Accumulation of senescent cells in adipose tissue plays an important role in obesity and age-related diseases. SIRT3, located in the mitochondria, can regulate ROS via different pathways. Thus, targeting SIRT3 activating compounds such as EGCG may delay senescence of cells and senescence induced inflammatory processes

MiRNA-based “fitness score” to assess the individual response to diet, metabolism, and exercise

Background Regular, especially sustained exercise plays an important role in the prevention and treatment of multiple chronic diseases. Some of the underlying molecular and cellular mechanisms behind the adaptive response to physical activity are still unclear, but recent findings suggest a possible role of epigenetic mechanisms, especially miRNAs, in the progression and management of exercise-related changes. Due to the combination of the analysis of epigenetic biomarkers (miRNAs), the intake of food and supplements, and genetic dispositions, a “fitness score” was evaluated to assess the individual response to nutrition, exercise, and metabolic influence. Methods In response to a 12-week sports intervention, we analyzed genetic and epigenetic biomarkers in capillary blood from 61 sedentary, healthy participants (66.1% females, 33.9% males, mean age 33 years), including Line-1 methylation, three SNPs, and ten miRNAs using HRM and qPCR analysis. These biomarkers were also analyzed in a healthy, age- and sex-matched control group (n, 20) without intervention. Food frequency intake, including dietary supplement intake, and general health questionnaires were surveyed under the supervision of trained staff. Results Exercise training decreased the expression of miR-20a-5p, −22-5p, and −505-3p (p < 0.02) and improved the “fitness score,” which estimates eight different lifestyle factors to assess, nutrition, inflammation, cardiovascular fitness, injury risk, regeneration, muscle and hydration status, as well as stress level. In addition, we were able to determine correlations between individual miRNAs, miR-20a-5p, −22-5p, and −101-3p (p < 0.04), and the genetic predisposition for endurance and/or strength and obesity risk (ACE, ACTN3, and FTO), as well as between miRNAs and the body composition (p < 0.05). MiR-19b-3p and −101-3p correlated with the intake of B vitamins. Further, miR-19b-3p correlated with magnesium and miR-378a-3p with iron intake (p < 0.05). Conclusions In summary, our results indicate that a combined analysis of several biomarkers (miRNAs) can provide information about an individual’s training adaptions/fitness, body composition, nutritional needs, and possible recovery. In contrast to most studies using muscle biopsies, we were able to show that these biomarkers can also be measured using a minimally invasive method

Five Days Periodic Fasting Elevates Levels of Longevity Related <i>Christensenella</i> and Sirtuin Expression in Humans

Periodic fasting (PF) is an increasingly popular approach that assists in the management of metabolic and inflammatory diseases as well as in preventing mechanisms involved in aging. However, little is known about the effects of fasting on gut microbiota and its impact on the epigenetic regulation of metabolically relevant enzymes, especially sirtuins (SIRTs). We analyzed the effect of periodic fasting on the human gut microbiota, SIRTs expression, and mitochondrial content in 51 males and females. The participants fasted under supervision for five consecutive days following the Buchinger fasting guidelines. Ketogenesis, selected mRNAs, miRNAs, mitochondrial (mt) DNA, and gut composition were analyzed before and after PF. PF triggered a significant switch in metabolism, as indicated by the increase in ß-hydroxybutyrate (BHB) and pyruvate dehydrogenase kinase isoform 4 (PDK4) expression in the capillary blood. MtDNA, SIRT1, SIRT3, and miRlet7b-5p expression in blood cells were elevated, whereas SIRT6 and miR125b-5p were not affected. Following fasting, gut microbiota diversity increased, and a statistically significant correlation between SIRT1 gene expression and the abundance of Prevotella and Lactobacillus was detected. The abundance of longevity related Christensenella species increased after fasting and inversely correlated with age as well as body mass index (BMI). Thus, this represents the first study that showing that fasting not only changes the composition of the gut microbiota, making it more diverse, but also affects SIRT expression in humans