Browsing by Subject "YOUNG"

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  • Marshall, H. H.; Johnstone, R. A.; Thompson, F. J.; Nichols, H. J.; Wells, D.; Hoffman, J. I.; Kalema-Zikusoka, G.; Sanderson, J. L.; Vitikainen, E. I. K.; Blount, J. D.; Cant, M. A. (2021)
    Rawls argued that fairness in human societies can be achieved if decisions about the distribution of societal rewards are made from behind a veil of ignorance, which obscures the personal gains that result. Whether ignorance promotes fairness in animal societies, that is, the distribution of resources to reduce inequality, is unknown. Here we show experimentally that cooperatively breeding banded mongooses, acting from behind a veil of ignorance over kinship, allocate postnatal care in a way that reduces inequality among offspring, in the manner predicted by a Rawlsian model of cooperation. In this society synchronized reproduction leaves adults in a group ignorant of the individual parentage of their communal young. We provisioned half of the mothers in each mongoose group during pregnancy, leaving the other half as matched controls, thus increasing inequality among mothers and increasing the amount of variation in offspring birth weight in communal litters. After birth, fed mothers provided extra care to the offspring of unfed mothers, not their own young, which levelled up initial size inequalities among the offspring and equalized their survival to adulthood. Our findings suggest that a classic idea of moral philosophy also applies to the evolution of cooperation in biological systems. Obscuring knowledge of personal gains from individuals can theoretically maintain fairness in a cooperative group. Experiments show that wild, cooperatively breeding banded mongooses uncertain of kinship allocate postnatal care in a way that reduces inequality among offspring, suggesting a classic idea of moral philosophy can apply in biological systems.
  • Carlsson, Annelie; Shepherd, Maggie; Ellard, Sian; Weedon, Michael; Lernmark, Ake; Forsander, Gun; Colclough, Kevin; Brahimi, Qefsere; Valtonen-Andre, Camilla; Ivarsson, Sten A.; Elding Larsson, Helena; Samuelsson, Ulf; Ortqvist, Eva; Groop, Leif; Ludvigsson, Johnny; Marcus, Claude; Hattersley, Andrew T. (2020)
    OBJECTIVE Identifying maturity-onset diabetes of the young (MODY) in pediatric populations close to diabetes diagnosis is difficult. Misdiagnosis and unnecessary insulin treatment are common. We aimed to identify the discriminatory clinical features at diabetes diagnosis of patients with glucokinase (GCK), hepatocyte nuclear factor-1A (HNF1A), and HNF4A MODY in the pediatric population. RESEARCH DESIGN AND METHODS Swedish patients (n = 3,933) aged 1-18 years, diagnosed with diabetes May 2005 to December 2010, were recruited from the national consecutive prospective cohort Better Diabetes Diagnosis. Clinical data, islet autoantibodies (GAD insulinoma antigen-2, zinc transporter 8, and insulin autoantibodies), HLA type, and C-peptide were collected at diagnosis. MODY was identified by sequencing GCK, HNF1A, and HNF4A, through either routine clinical or research testing. RESULTS The minimal prevalence of MODY was 1.2%. Discriminatory factors for MODY at diagnosis included four islet autoantibody negativity (100% vs. 11% not-known MODY; P = 2 x 10(-44)), HbA(1c) (7.0% vs. 10.7% [53 vs. 93 mmol/mol]; P = 1 x 10(-20)), plasma glucose (11.7 vs. 26.7 mmol/L; P = 3 x 10(-19)), parental diabetes (63% vs. 12%; P = 1 x 10(-15)), and diabetic ketoacidosis (0% vs. 15%; P = 0.001). Testing 303 autoantibody-negative patients identified 46 patients with MODY (detection rate 15%). Limiting testing to the 73 islet autoantibody-negative patients with HbA(1c)
  • Kettunen, Jarno L. T.; Parviainen, Helka; Miettinen, Päivi J.; Färkkilä, Martti; Tamminen, Marjo; Salonen, Pia; Lantto, Eila; Tuomi, Tiinamaija (2017)
    Context: The clinical spectrum of organogenetic anomalies associated with HNF1B mutations is heterogeneous. Besides cystic kidney disease, diabetes, and various other manifestations, odd cases of mainly neonatal and posttransplantation cholestasis have been described. The biliary phenotype is incompletely defined. Objective: To systematically characterize HNF1B-related anomalies in the bile ducts by imaging with magnetic resonance imaging (MRI) or magnetic resonance cholangiopancreatography (MRCP). Setting and Patients: Fourteen patients with HNF1B mutations in the catchment area of the Helsinki University Hospital were evaluated with upper abdominal MRI and MRCP. Blood samples and clinical history provided supplemental data on the individual phenotype. Main Outcome Measure(s): Structural anomalies in the biliary system, medical history of cholestasis, other findings in abdominal organs, diabetes and antihyperglycemic treatment, hypomagnesemia, and hyperuricemia. Results: Structural anomalies of the bile ducts were found in seven of 14 patients (50%). Six patients had choledochal cysts, which are generally considered premalignant. Conclusions: Structural anomalies of the biliary system were common in HNF1B mutation carriers. The malignant potential of HNF1B-associated choledochal cysts warrants further studies.
  • Allegaert, Karel; Olkkola, Klaus T.; Owens, Katie H.; Van de Velde, Marc; de Maat, Monique M.; Anderson, Brian J.; PACIA Study Grp (2014)
  • European Soc Human Genetics; European Council Legal Med; European Soc Cardiology Working; European Reference Network Rare; Assoc European Cardiovasc; Fellmann, Florence; van El, Carla G.; Sajantila, Antti (2019)
    Sudden cardiac death (SCD) accounts for 10-20% of total mortality, i.e., one in five individuals will eventually die suddenly. Given the substantial genetic component of SCD in younger cases, postmortem genetic testing may be particularly useful in elucidating etiological factors in the cause of death in this subset. The identification of genes responsible for inherited cardiac diseases have led to the organization of cardiogenetic consultations in many countries worldwide. Expert recommendations are available, emphasizing the importance of genetic testing and appropriate information provision of affected individuals, as well as their relatives. However, the context of postmortem genetic testing raises some particular ethical, legal, and practical (including economic or financial) challenges. The Public and Professional Policy Committee of the European Society of Human Genetics (ESHG), together with international experts, developed recommendations on management of SCD after a workshop sponsored by the Brocher Foundation and ESHG in November 2016. These recommendations have been endorsed by the ESHG Board, the European Council of Legal Medicine, the European Society of Cardiology working group on myocardial and pericardial diseases, the ERN GUARD-HEART, and the Association for European Cardiovascular Pathology. They emphasize the importance of increasing the proportion of both medical and medicolegal autopsies and educating the professionals. Multidisciplinary collaboration is of utmost importance. Public funding should be allocated to reach these goals and allow public health evaluation.
  • Juntunen, Miia; Heinonen, Sini; Huhtala, Heini; Rissanen, Aila; Kaprio, Jaakko; Kuismanen, Kirsi; Pietiläinen, Kirsi H.; Miettinen, Susanna; Patrikoski, Mimmi (2021)
    Background Adipose stromal/stem cells (ASCs) are promising candidates for future clinical applications. ASCs have regenerative capacity, low immunogenicity, and immunomodulatory ability. The success of future cell-based therapies depends on the appropriate selection of donors. Several factors, including age, sex, and body mass index (BMI), may influence ASC characteristics. Our aim was to investigate the effect of acquired weight on ASC characteristics under the same genetic background using ASCs derived from monozygotic (MZ) twin pairs. Methods ASCs were isolated from subcutaneous adipose tissue from five weight-discordant (WD, within-pair difference in BMI > 3 kg/m(2)) MZ twin pairs, with measured BMI and metabolic status. The ASC immunophenotype, proliferation and osteogenic and adipogenic differentiation capacity were studied. ASC immunogenicity, immunosuppression capacity and the expression of inflammation markers were investigated. ASC angiogenic potential was assessed in cocultures with endothelial cells. Results ASCs showed low immunogenicity, proliferation, and osteogenic differentiation capacity independent of weight among all donors. ASCs showed a mesenchymal stem cell-like immunophenotype; however, the expression of CD146 was significantly higher in leaner WD twins than in heavier cotwins. ASCs from heavier twins from WD pairs showed significantly greater adipogenic differentiation capacity and higher expression of TNF and lower angiogenic potential compared with their leaner cotwins. ASCs showed immunosuppressive capacity in direct cocultures; however, heavier WD twins showed stronger immunosuppressive capacity than leaner cotwins. Conclusions Our genetically matched data suggest that a higher weight of the donor may have some effect on ASC characteristics, especially on angiogenic and adipogenic potential, which should be considered when ASCs are used clinically.
  • Karppinen, Jari E.; Rottensteiner, Mirva; Wiklund, Petri; Hamalainen, Kaisa; Laakkonen, Eija K.; Kaprio, Jaakko; Kainulainen, Heikki; Kujala, Urho M. (2019)
    Purpose We aimed to investigate if hereditary factors, leisure-time physical activity (LTPA) and metabolic health interact with resting fat oxidation (RFO) and peak fat oxidation (PFO) during ergometer cycling. Methods We recruited 23 male monozygotic twin pairs (aged 32-37 years) and determined their RFO and PFO with indirect calorimetry for 21 and 19 twin pairs and for 43 and 41 twin individuals, respectively. Using physical activity interviews and the Baecke questionnaire, we identified 10 twin pairs as LTPA discordant for the past 3 years. Of the twin pairs, 8 pairs participated in both RFO and PFO measurements, and 2 pairs participated in either of the measurements. We quantified the participants' metabolic health with a 2-h oral glucose tolerance test. Results Fat oxidation within co-twins was correlated at rest [intraclass correlation coefficient (ICC) = 0.54, 95% confidence interval (CI) 0.15-0.78] and during exercise (ICC = 0.67, 95% CI 0.33-0.86). The LTPA-discordant pairs had no pairwise differences in RFO or PFO. In the twin individual-based analysis, PFO was positively correlated with the past 12-month LTPA (r = 0.26, p = 0.034) and the Baecke score (r = 0.40, p = 0.022) and negatively correlated with the area under the curve of insulin (r = - 0.42, p = 0.015) and glucose (r = - 0.31, p = 0.050) during the oral glucose tolerance test. Conclusions Hereditary factors were more important than LTPA for determining fat oxidation at rest and during exercise. Additionally, PFO, but not RFO, was associated with better metabolic health.
  • Leroy, Adam K.; Bolatto, Alberto D.; Ostriker, Eve C.; Walter, Fabian; Gorski, Mark; Ginsburg, Adam; Krieger, Nico; Levy, Rebecca C.; Meier, David S.; Mills, Elisabeth; Ott, Juergen; Rosolowsky, Erik; Thompson, Todd A.; Veilleux, Sylvain; Zschaechner, Laura K. (2018)
    NGC 253 hosts the nearest nuclear starburst. Previous observations show a region rich in molecular gas, with dense clouds associated with recent star formation. We used the Atacama Large Submillimeter/Millimeter Array (ALMA) to image the 350 GHz dust continuum and molecular line emission from this region at 2 pc resolution. Our observations reveal similar to 14 bright, compact (similar to 2-3 pc FWHM) knots of dust emission. Most of these sources are likely to be forming super star clusters (SSCs) based on their inferred dynamical and gas masses, association with 36 GHz radio continuum emission, and coincidence with line emission tracing dense, excited gas. One source coincides with a known SSC, but the rest remain invisible in Hubble near-infrared (IR) imaging. Our observations imply that gas still constitutes a large fraction of the overall mass in these sources. Their high brightness temperature at 350 GHz also implies a large optical depth near the peak of the IR spectral energy distribution. As a result, these sources may have large IR photospheres, and the IR radiation force likely exceeds L/c. Still, their moderate observed velocity dispersions suggest that feedback from radiation, winds, and supernovae are not yet disrupting most sources. This mode of star formation appears to produce a large fraction of stars in the burst. We argue for a scenario in which this phase lasts similar to 1 Myr, after which the clusters shed their natal cocoons but continue to produce ionizing photons. The strong feedback that drives the observed cold gas and X-ray outflows likely occurs after the clusters emerge from this early phase.
  • Patel, Kashyap A.; Kettunen, Jarno; Laakso, Markku; Stancakova, Alena; Laver, Thomas W.; Colclough, Kevin; Johnson, Matthew B.; Abramowicz, Marc; Groop, Leif; Miettinen, Paivi J.; Shepherd, Maggie H.; Flanagan, Sarah E.; Ellard, Sian; Inagaki, Nobuya; Hattersley, Andrew T.; Tuomi, Tiinamaija; Cnop, Miriam; Weedon, Michael N. (2017)
    Finding new causes of monogenic diabetes helps understand glycaemic regulation in humans. To find novel genetic causes of maturity-onset diabetes of the young (MODY), we sequenced MODY cases with unknown aetiology and compared variant frequencies to large public databases. From 36 European patients, we identify two probands with novel RFX6 heterozygous nonsense variants. RFX6 protein truncating variants are enriched in the MODY discovery cohort compared to the European control population within ExAC (odds ratio = 131, P = 1 x 10(-4)). We find similar results in non-Finnish European (n = 348, odds ratio = 43, P = 5 x 10(-5)) and Finnish (n = 80, odds ratio = 22, P = 1 x 10(-6)) replication cohorts. RFX6 heterozygotes have reduced penetrance of diabetes compared to common HNF1A and HNF4A-MODY mutations (27, 70 and 55% at 25 years of age, respectively). The hyperglycaemia results from beta-cell dysfunction and is associated with lower fasting and stimulated gastric inhibitory polypeptide (GIP) levels. Our study demonstrates that heterozygous RFX6 protein truncating variants are associated with MODY with reduced penetrance.
  • Hekkala, Anne M.; Ilonen, Jorma; Toppari, Jorma; Knip, Mikael; Veijola, Riitta (2018)
    We studied the frequency of diabetic ketoacidosis (DKA) in children at diagnosis of type 1 diabetes (T1D) in a region where newborn infants have since 1995 been recruited for genetic screening for human leukocyte antigen (HLA)-conferred disease susceptibility and prospective follow up. The aim was to study whether participation in newborn screening and follow up affected the frequency of DKA, and to follow the time trends in DKA frequency. We first included children born in Oulu University Hospital since 1995 when the prospective studies have been ongoing and diagnosed with T1D
  • Nyholm, Iiris; Hukkinen, Maria; Koivusalo, Antti; Merras-Salmio, Laura; Kolho, Kaija-Leena; Rintala, Risto J.; Pakarinen, Mikko P. (2019)
    Background and Aims Childhood-onset ulcerative colitis [UC] requires total colectomy in one-quarter of patients at some point of their disease. The study objective was to evaluate long-term outcomes after proctocolectomy with ileoanal anastomosis [IAA] for paediatric UC. Methods Medical records of all children undergoing proctocolectomy with IAA for UC during 1985-2016 in Helsinki University Hospital were retrospectively assessed. Data on disease history, diagnostic and operative details, occurrence of surgical complications, functional outcome, postoperative diagnosis of Crohn's disease [CD] and pouch failure were collected. Risk factors for IAA failure were analysed with Cox regression. Results Of 87 patients, 85 [98%] had UC and 2 [2%] inflammatory bowel disease unclassified [IBD-U] preoperatively. Altogether 66% underwent two-stage and 34% underwent three-stage procedures. During 7.8 [4.1-14.5] years' follow-up, nine [10%] patients were diagnosed with postoperative CD. Postoperative leakages [n = 8, 9%] and strictures [n = 10, 11%] were equally common, whereas fistulas [78% vs 9%, p Conclusions For paediatric UC, long-term surgical and functional outcomes after proctocolectomy with IAA are reassuring. Need for three-stage surgery and occurrence of postoperative fistulas and abscesses, but not leakages or strictures, associate with postoperative CD diagnosis and the risk for ileostomy.
  • Ellul, Susan; Wake, Melissa; Clifford, Susan A.; Lange, Katherine; Würtz, Peter; Juonala, Markus; Dwyer, Terence; Carlin, John B.; Burgner, David P.; Saffery, Richard (2019)
    Objectives Nuclear magnetic resonance (NMR) metabolomics is high throughput and cost-effective, with the potential to improve the understanding of disease and risk. We examine the circulating metabolic profile by quantitative NMR metabolomics of a sample of Australian 11-12 year olds children and their parents, describe differences by age and sex, and explore the correlation of metabolites in parent-child dyads. Design The population-based cross-sectional Child Health CheckPoint study nested within the Longitudinal Study of Australian Children. Setting Blood samples collected from CheckPoint participants at assessment centres in seven Australian cities and eight regional towns; February 2015-March 2016. Participants 1180 children and 1325 parents provided a blood sample and had metabolomics data available. This included 1133 parent-child dyads (518 mother-daughter, 469 mother-son, 68 father-daughter and 78 father-son). Outcome measures 228 metabolic measures were obtained for each participant. We focused on 74 biomarkers including amino acid species, lipoprotein subclass measures, lipids, fatty acids, measures related to fatty acid saturation, and composite markers of inflammation and energy homeostasis. Results We identified differences in the concentration of specific metabolites between childhood and adulthood and in metabolic profiles in children and adults by sex. In general, metabolite concentrations were higher in adults than children and sex differences were larger in adults than in children. Positive correlations were observed for the majority of metabolites including isoleucine (CC 0.33, 95% CI 0.27 to 0.38), total cholesterol (CC 0.30, 95% CI 0.24 to 0.35) and omega 6 fatty acids (CC 0.28, 95% CI 0.23 to 0.34) in parent-child comparisons. Conclusions We describe the serum metabolite profiles from mid-childhood and adulthood in a population-based sample, together with a parent-child concordance. Differences in profiles by age and sex were observed. These data will be informative for investigation of the childhood origins of adult non-communicable diseases and for comparative studies in other populations.
  • Talman, Virpi; Teppo, Jaakko Sakari; Pöhö, Päivi Anneli; Movahedi, Parisa; Vaikkinen, Anu; Karhu, Suvi Tuuli; Trošt, Kajetan; Suvitaival, Tommi; Heikkonen, Jukka; Pahikkala, Tapio; Kotiaho, Ahti Antti Tapio; Kostiainen, Risto Kalervo; Varjosalo, Markku Tapio; Ruskoaho, Heikki Juhani (2018)
    Background The molecular mechanisms mediating postnatal loss of cardiac regeneration in mammals are not fully understood. We aimed to provide an integrated resource of mRNA, protein, and metabolite changes in the neonatal heart for identification of metabolism‐related mechanisms associated with cardiac regeneration. Methods and Results Methods and results Mouse ventricular tissue samples taken on postnatal day 1 (P01), P04, P09, and P23 were analyzed with RNA sequencing and global proteomics and metabolomics. Gene ontology analysis, KEGG pathway analysis, and fuzzy c‐means clustering were used to identify up‐ or downregulated biological processes and metabolic pathways on all 3 levels, and Ingenuity pathway analysis (Qiagen) was used to identify upstream regulators. Differential expression was observed for 8547 mRNAs and for 1199 of 2285 quantified proteins. Furthermore, 151 metabolites with significant changes were identified. Differentially regulated metabolic pathways include branched chain amino acid degradation (upregulated at P23), fatty acid metabolism (upregulated at P04 and P09; downregulated at P23) as well as the HMGCS (HMG‐CoA [hydroxymethylglutaryl‐coenzyme A] synthase)–mediated mevalonate pathway and ketogenesis (transiently activated). Pharmacological inhibition of HMGCS in primary neonatal cardiomyocytes reduced the percentage of BrdU‐positive cardiomyocytes, providing evidence that the mevalonate and ketogenesis routes may participate in regulating the cardiomyocyte cell cycle. Conclusions This study is the first systems‐level resource combining data from genomewide transcriptomics with global quantitative proteomics and untargeted metabolomics analyses in the mouse heart throughout the early postnatal period. These integrated data of molecular changes associated with the loss of cardiac regeneration may open up new possibilities for the development of regenerative therapies
  • Gyllenberg, Frida; Saloranta, Tuire; But, Anna; Gissler, Mika; Heikinheimo, Oskari (2020)
    Objective: To identify factors associated with choosing long-acting reversible contraception (LARC) (intrauterine device or contraceptive implant), when provided free-of-charge. Study design: This register-based cohort study comprises all women living in the city of Vantaa in the Helsinki metropolitan area during 2013-2014, with information on LARC initiations retrieved from electronic health records. Since January 2013, women in Vantaa can receive their first LARC method free-of-charge at public contraceptive clinics. We performed multivariable regression to assess seven predictors based on literature and four predictors based on gynecological history for association with choosing LARC in this population. Results: In 2013-2014, 9669 women entitled to a free-of-charge method visited a public clinic and 2035 (21.0%) women initiated LARC. Factors most associated with LARC initiation included history of delivery (odds ratio [OR] 5.4, 95% confidence intervals [CI] 4.7-6.2) and induced abortion (OR 1.4, 95%CI 1.2-1.6), and no previous visit at the clinic (OR 1.3, 95%CI 1.2-1.5). Previous delivery was associated with LARC initiation in all age-groups (OR, 95%CI by age-group; 15-19 years: 10.8, 5.1-23.4; 20-24 years: 6.4, 4.9-8.3; 25-29 years: 6.7, 5.2-8.6; 30-44 years: 3.6, 2.9-4.6). Conclusion: History of delivery and induced abortion were strongly associated with choosing a LARC method, even though all women in the population were entitled to their first free-of-charge LARC method. The association was particularly strong among women less than 25 years of age. Implications statement: Untargeted provision of free-of-charge LARC in public contraceptive services reached women with previous delivery or abortion well during the programs first years. However, as LARCs are recommended to all women, future research should focus on how uptake evolves and how to reach all women in need of long-term, effective contraception. (C) 2020 Elsevier Inc. All rights reserved.
  • Cole-Kodikara, Elizabeth M.; Käpylä, Maarit J.; Lehtinen, Jyri J.; Hackman, Thomas; Ilyin, Ilya; Piskunov, Nikolai; Kochukhov, Oleg (2019)
    Context. LQ Hya is one of the most frequently studied young solar analogue stars. Recently, it has been observed to show intriguing behaviour when analysing long-term photometry. For instance, from 2003-2009, a coherent spot structure migrating in the rotational frame was reported by various authors. However, ever since, the star has entered a chaotic state where coherent structures seem to have disappeared and rapid phase jumps of the photometric minima occur irregularly over time. Aims. LQ Hya is one of the stars included in the SOFIN/FIES long-term monitoring campaign extending over 25 yr. Here, we publish new temperature maps for the star during 2006-2017, covering the chaotic state of the star. Methods. We used a Doppler imaging technique to derive surface temperature maps from high-resolution spectra. Results. From the mean temperatures of the Doppler maps, we see a weak but systematic increase in the surface temperature of the star. This is consistent with the simultaneously increasing photometric magnitude. During nearly all observing seasons, we see a high-latitude spot structure which is clearly non-axisymmetric. The phase behaviour of this structure is very chaotic but agrees reasonably well with the photometry. Equatorial spots are also frequently seen, but we interpret many of them to be artefacts due to the poor to moderate phase coverage. Conclusions. Even during the chaotic phase of the star, the spot topology has remained very similar to the higher activity epochs with more coherent and long-lived spot structures. In particular, we see high-latitude and equatorial spot activity, the mid latitude range still being most often void of spots. We interpret the erratic jumps and drifts in phase of the photometric minima to be caused by changes in the high-latitude spot structure rather than the equatorial spots.
  • Heikinheimo-Connell, Terttu; Chimbayo, Daniel; Kumwenda, Johnstone J.; Kampondeni, Sam; Allain, Theresa J. (2012)
  • Masip-Manuel, Guiomar; Silventoinen, Karri; Keski-Rahkonen, Anna; Palviainen, Teemu; Sipilä, Pyry N.; Kaprio, Jaakko; Bogl, Leonie H. (2020)
    Background Obesity susceptibility genes are highly expressed in the brain suggesting that they might exert their influence on body weight through eating-related behaviors. Objectives To examine whether the genetic susceptibility to obesity is mediated by eating behavior patterns. Methods Participants were 3977 twins (33% monozygotic, 56% females), aged 31–37 y, from wave 5 of the FinnTwin16 study. They self-reported their height and weight, eating behaviors (15 items), diet quality, and self-measured their waist circumference (WC). For 1055 twins with genome-wide data, we constructed a polygenic risk score for BMI (PRSBMI) using almost 1 million single nucleotide polymorphisms. We used principal component analyses to identify eating behavior patterns, twin modeling to decompose correlations into genetic and environmental components, and structural equation modeling to test mediation models between the PRSBMI, eating behavior patterns, and obesity measures. Results We identified 4 moderately heritable (h2 = 36–48%) eating behavior patterns labeled “snacking,” “infrequent and unhealthy eating,” “avoidant eating,” and “emotional and external eating.” The highest phenotypic correlation with obesity measures was found for the snacking behavior pattern (r = 0.35 for BMI and r = 0.32 for WC; P < 0.001 for both), largely due to genetic factors in common (bivariate h2 > 70%). The snacking behavior pattern partially mediated the association between the PRSBMI and obesity measures (βindirect = 0.06; 95% CI: 0.02, 0.09; P = 0.002 for BMI; and βindirect = 0.05; 95% CI: 0.02, 0.08; P = 0.003 for WC). Conclusions Eating behavior patterns share a common genetic liability with obesity measures and are moderately heritable. Genetic susceptibility to obesity can be partly mediated by an eating pattern characterized by frequent snacking. Obesity prevention efforts might therefore benefit from focusing on eating behavior change, particularly in genetically susceptible individuals.
  • Schuijt, Tim J.; Lankelma, Jacqueline M.; Scicluna, Brendon P.; e Melo, Felipe de Sousa; Roelofs, Joris J. T. H.; de Boer, J. Daan; Hoogendijk, Arjan J.; de Beer, Regina; de Vos, Alex; Belzer, Clara; de Vos, Willem M.; van der Poll, Tom; Wiersinga, W. Joost (2016)
    Objective Pneumonia accounts for more deaths than any other infectious disease worldwide. The intestinal microbiota supports local mucosal immunity and is increasingly recognised as an important modulator of the systemic immune system. The precise role of the gut microbiota in bacterial pneumonia, however, is unknown. Here, we investigate the function of the gut microbiota in the host defence against Streptococcus pneumoniae infections. Design We depleted the gut microbiota in C57BL/6 mice and subsequently infected them intranasally with S. pneumoniae. We then performed survival and faecal microbiota transplantation (FMT) experiments and measured parameters of inflammation and alveolar macrophage whole-genome responses. Results We found that the gut microbiota protects the host during pneumococcal pneumonia, as reflected by increased bacterial dissemination, inflammation, organ damage and mortality in microbiota-depleted mice compared with controls. FMT in gut microbiota-depleted mice led to a normalisation of pulmonary bacterial counts and tumour necrosis factor-alpha and interleukin-10 levels 6 h after pneumococcal infection. Whole-genome mapping of alveolar macrophages showed upregulation of metabolic pathways in the absence of a healthy gut microbiota. This upregulation correlated with an altered cellular responsiveness, reflected by a reduced responsiveness to lipopolysaccharide and lipoteichoic acid. Compared with controls, alveolar macrophages derived from gut microbiota-depleted mice showed a diminished capacity to phagocytose S. pneumoniae. Conclusions This study identifies the intestinal microbiota as a protective mediator during pneumococcal pneumonia. The gut microbiota enhances primary alveolar macrophage function. Novel therapeutic strategies could exploit the gut-lung axis in bacterial infections.