The methylome of the gut microbiome : disparate Dam methylation patterns in intestinal Bacteroides dorei

Peer reviewe

Integrative analyses of TEDDY Omics data reveal lipid metabolism abnormalities, increased intracellular ROS and heightened inflammation prior to autoimmunity for type 1 diabetes

27 páginas, 6 figuras, Contiene material suplementarioBackground: The Environmental Determinants of Diabetes in the Young (TEDDY) is a prospective birth cohort designed to study type 1 diabetes (T1D) by following children with high genetic risk. An integrative multi-omics approach was used to evaluate islet autoimmunity etiology, identify disease biomarkers, and understand progression over time. Results: We identify a multi-omics signature that was predictive of islet autoimmunity (IA) as early as 1 year before seroconversion. At this time, abnormalities in lipid metabolism, decreased capacity for nutrient absorption, and intracellular ROS accumulation are detected in children progressing towards IA. Additionally, extracellular matrix remodeling, inflammation, cytotoxicity, angiogenesis, and increased activity of antigen-presenting cells are observed, which may contribute to beta cell destruction. Our results indicate that altered molecular homeostasis is present in IA-developing children months before the actual detection of islet autoantibodies, which opens an interesting window of opportunity for therapeutic intervention. Conclusions: The approach employed herein for assessment of the TEDDY cohort showcases the utilization of multi-omics data for the modeling of complex, multifactorial diseases, like T1D.This study was supported by grant 2015PG-T1D050 provided by the Leona M. and Harry B. Helmsley Charitable Trust. The TEDDY Study is funded by U01 DK63829, U01 DK63861, U01 DK63821, U01 DK63865, U01 DK63863, U01 DK63836, U01 DK63790, UC4 DK63829, UC4 DK63861, UC4 DK63821, UC4 DK63865, UC4 DK63863, UC4 DK63836, UC4 DK95300, UC4 DK100238, UC4 DK106955, UC4 DK112243, UC4 DK117483, and Contract No. HHSN267200700014C from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Child Health and Human Development (NICHD), National Institute of Environmental Health Sciences (NIEHS), Centers for Disease Control and Prevention (CDC), and JDRF. This work was supported in part by the NIH/NCATS Clinical and Translational Science Awards to the University of Florida (UL1 TR000064) and the University of Colorado (UL1 TR001082).Peer reviewe

Bacteroides dorei dominates gut microbiome prior to autoimnnunity in Finnish children at high risk for type 1 diabetes

Peer reviewe

Meconium microbiome analysis identifies bacteria correlated with premature birth.

Preterm birth is the second leading cause of death in children under the age of five years worldwide, but the etiology of many cases remains enigmatic. The dogma that the fetus resides in a sterile environment is being challenged by recent findings and the question has arisen whether microbes that colonize the fetus may be related to preterm birth. It has been posited that meconium reflects the in-utero microbial environment. In this study, correlations between fetal intestinal bacteria from meconium and gestational age were examined in order to suggest underlying mechanisms that may contribute to preterm birth.Meconium from 52 infants ranging in gestational age from 23 to 41 weeks was collected, the DNA extracted, and 16S rRNA analysis performed. Resulting taxa of microbes were correlated to clinical variables and also compared to previous studies of amniotic fluid and other human microbiome niches.Increased detection of bacterial 16S rRNA in meconium of infants of <33 weeks gestational age was observed. Approximately 61·1% of reads sequenced were classified to genera that have been reported in amniotic fluid. Gestational age had the largest influence on microbial community structure (R = 0·161; p = 0·029), while mode of delivery (C-section versus vaginal delivery) had an effect as well (R = 0·100; p = 0·044). Enterobacter, Enterococcus, Lactobacillus, Photorhabdus, and Tannerella, were negatively correlated with gestational age and have been reported to incite inflammatory responses, suggesting a causative role in premature birth.This provides the first evidence to support the hypothesis that the fetal intestinal microbiome derived from swallowed amniotic fluid may be involved in the inflammatory response that leads to premature birth

Development of a Distance Education Program by a Land-Grant University Augments the 2-Year to 4-Year STEM Pipeline and Increases Diversity in STEM

<div><p>Although initial interest in science, technology, engineering and mathematics (STEM) is high, recruitment and retention remains a challenge, and some populations are disproportionately underrepresented in STEM fields. To address these challenges, the Microbiology and Cell Science Department in the College of Agricultural and Life Sciences at the University of Florida has developed an innovative 2+2 degree program. Typical 2+2 programs begin with a student earning an associate’s degree at a local community college and then transferring to a 4-year institution to complete a bachelor’s degree. However, many universities in the United States, particularly land-grant universities, are located in rural regions that are distantly located from their respective states’ highly populated urban centers. This geographical and cultural distance could be an impediment to recruiting otherwise highly qualified and diverse students. Here, a new model of a 2+2 program is described that uses distance education as the vehicle to bring a research-intensive university’s life sciences curriculum to students rather than the oft-tried model of a university attempting to recruit underrepresented minority students to its location. In this paradigm, community college graduates transfer into the Microbiology and Cell Science program as distance education students to complete their Bachelor of Science degree. The distance education students’ experiences are similar to the on-campus students’ experiences in that both groups of students take the same department courses taught by the same instructors, take required laboratory courses in a face-to-face format, take only proctored exams, and have the same availability to instructors. Data suggests that a hybrid online transfer program may be a viable approach to increasing STEM participation (as defined by enrollment) and diversity. This approach is particularly compelling as the distance education cohort has comparable grade point averages and retention rates compared to the corresponding on-campus transfer cohort.</p></div

Distribution of races and ethnicities for the Fall 2014 enrollment in the Microbiology and Cell Science major within the College of Agricultural and Life Sciences.

<p>Racial/ethnic groups who are traditionally underrepresented in STEM fields are in blue while those groups who are not underrepresented in STEM are in green. The proportions of individuals with two or more races, nonresident aliens, or race unknown are represented in shades of gray.</p

Retention of transfer students who enrolled in the Microbiology and Cell Science major within the College of Agricultural and Life Sciences in Fall 2011 and Fall 2012.

<p>Retention equals the proportion of students who have graduated and persist in the program. Retention levels between the two cohorts are not statistically different (p = 0.10, two tailed Fisher's Exact Test).</p

Box plots representing the average grade point average (GPA) of MCS majors within CALS.

<p>The horizontal lines represent the median GPA of students in the Fall 2013 semester (left box plot) and at the time of graduation (right box plot). The boxes represent the interquartile range (IQR). The IQR includes the 50% of samples closest to the median. The lines above and below the IQR, represent either 1.5 times the IQR or the maximum range of the samples if that range is below 1.5 times the IQR. The dots above or below these lines represent outliers that are above or below 1.5 times the IQRs. As determined by Kruskal-Wallis, the on-campus cohort had a statistically higher mean GPA than the on-campus transfer cohort (p = 0.031) but not the DE MCS cohort (p = 0.118) in the Fall 2013 semester (H = 8.5, df = 2). The mean GPAs of the two transfer cohorts were not statistically different (p = 0.956). At the time of graduation, as depicted in the right box plot, the on-campus transfer cohort had a statistically lower mean GPA than the on-campus cohort (p = 0.00016), but there was no statistical difference between the mean graduating GPAs of the on-campus and DE MCS students (p = 0.995) nor the on-campus transfer and DE MCS cohort (p = 0.269) (H = 16.5, df = 2).</p

Enrollment by students into the Microbiology and Cell Science major across time.

<p>a) transfer student enrollments in the on-campus (blue) and distance education (red) and b) first time in college (FTIC) students enrolled in the College of Agricultural and Life Science (blue) or College of Liberal Arts and Sciences (red) Microbiology and Cell Science major.</p

Inflammatory marker S100A12 was correlated with gestational age.

<p>(A) Non-metric multidimensional scaling ordination plot depicting the relatedness of the bacterial communities from all meconium samples; communities from >33 week infants (blue) clustered more closely than those from <33 week infants (red). Analysis of similarity (ANOSIM) revealed that gestational age (<33 and >33 weeks) had the largest effect on meconium microbial structure (R = 0·16; p-value = 0·03). (B) Of the four predominant phyla, the relative abundance of Firmicutes and Actinobacteria was correlated with low gestational age (**p<0·01 & *p<0·05, respectively). (C) Genera negatively correlated with gestational age (**p<0·01) are presented. (D) Genera associated with mode of delivery (*p<0·05) were observed, though these differences are not as pronounced as the genera associated with gestational age.</p