Development of the preterm infant gut microbiome: a research priority.

The very low birth weight (VLBW) infant is at great risk for marked dysbiosis of the gut microbiome due to multiple factors, including physiological immaturity and prenatal/postnatal influences that disrupt the development of a normal gut flora. However, little is known about the developmental succession of the microbiota in preterm infants as they grow and mature. This review provides a synthesis of our understanding of the normal development of the infant gut microbiome and contrasts this with dysbiotic development in the VLBW infant. The role of human milk in normal gut microbial development is emphasized, along with the role of the gut microbiome in immune development and gastroenteric health. Current research provides evidence that the gut microbiome interacts extensively with many physiological systems and metabolic processes in the developing infant. However, to the best of our knowledge, there are currently no studies prospectively mapping the gut microbiome of VLBW infants through early childhood. This knowledge gap must be filled to inform a healthcare system that can provide for the growth, health, and development of VLBW infants. The paper concludes with speculation about how the VLBW infants' gut microbiome might function through host-microbe interactions to contribute to the sequelae of preterm birth, including its influence on growth, development, and general health of the infant host

Dichotomous development of the gut microbiome in preterm infants.

BackgroundPreterm infants are at risk of developing intestinal dysbiosis with an increased proportion of Gammaproteobacteria. In this study, we sought the clinical determinants of the relative abundance of feces-associated Gammaproteobacteria in very low birth weight (VLBW) infants. Fecal microbiome was characterized at ≤ 2 weeks and during the 3rd and 4th weeks after birth, by 16S rRNA amplicon sequencing. Maternal and infant clinical characteristics were extracted from electronic medical records. Data were analyzed by linear mixed modeling and linear regression.ResultsClinical data and fecal microbiome profiles of 45 VLBW infants (gestational age 27.9 ± 2.2 weeks; birth weight 1126 ± 208 g) were studied. Three stool samples were analyzed for each infant at mean postnatal ages of 9.9 ± 3, 20.7 ± 4.1, and 29.4 ± 4.9 days. The average relative abundance of Gammaproteobacteria was 42.5% (0-90%) at ≤ 2 weeks, 69.7% (29.9-86.9%) in the 3rd, and 75.5% (54.5-86%) in the 4th week (p < 0.001). Hierarchical and K-means clustering identified two distinct subgroups: cluster 1 started with comparatively low abundance that increased with time, whereas cluster 2 began with a greater abundance at ≤ 2 weeks (p < 0.001) that decreased over time. Both groups resembled each other by the 3rd week. Single variants of Klebsiella and Staphylococcus described variance in community structure between clusters and were shared between all infants, suggesting a common, hospital-derived source. Fecal Gammaproteobacteria was positively associated with vaginal delivery and antenatal steroids.ConclusionsWe detected a dichotomy in gut microbiome assembly in preterm infants: some preterm infants started with low relative gammaproteobacterial abundance in stool that increased as a function of postnatal age, whereas others began with and maintained high abundance. Vaginal birth and antenatal steroids were identified as predictors of Gammaproteobacteria abundance in the early (≤ 2 weeks) and later (3rd and 4th weeks) stool samples, respectively. These findings are important in understanding the development of the gut microbiome in premature infants

Educating Future Nursing Scientists: Recommendations for Integrating Omics Content in PhD Programs

Preparing the next generation of nursing scientists to conduct high-impact, competitive, sustainable, innovative, and interdisciplinary programs of research requires that the curricula for PhD programs keep pace with emerging areas of knowledge and health care/biomedical science. A field of inquiry that holds great potential to influence our understanding of the underlying biology and mechanisms of health and disease is omics. For the purpose of this article, omics refers to genomics, transcriptomics, proteomics, epigenomics, exposomics, microbiomics, and metabolomics. Traditionally, most PhD programs in schools of nursing do not incorporate this content into their core curricula. As part of the Council for the Advancement of Nursing Science\u27s Idea Festival for Nursing Science Education, a work group charged with addressing omics preparation for the next generation of nursing scientists was convened. The purpose of this article is to describe key findings and recommendations from the work group that unanimously and enthusiastically support the incorporation of omics content into the curricula of PhD programs in nursing. The work group also calls to action faculty in schools of nursing to develop strategies to enable students needing immersion in omics science and methods to execute their research goals

Impact of Maternal Thyroperoxidase Status on Fetal Body and Brain Size

The obstetric consequences of abnormal thyroid function during pregnancy have been established. Less understood is the influence of maternal thyroid autoantibodies on infant outcomes. The objective of this study was to examine the influence of maternal thyroperoxidase (TPO) status on fetal/infant brain and body growth. Six-hundred thirty-one (631) euthyroid pregnant women were recruited from prenatal clinics in Tampa Bay, Florida, and the surrounding area between November 2007 and December 2010. TPO status was determined during pregnancy and fetal/infant brain and body growth variables were assessed at delivery. Regression analysis revealed maternal that TPO positivity was significantly associated with smaller head circumference, reduced brain weight, and lower brain-to-body ratio among infants born to TPO+ white, non-Hispanic mothers only, distinguishing race/ethnicity as an effect modifier in the relationship. No significant differences were noted in body growth measurements among infants born to TPO positive mothers of any racial/ethnic group. Currently, TPO antibody status is not assessed as part of the standard prenatal care laboratory work-up, but findings from this study suggest that fetal brain growth may be impaired by TPO positivity among certain populations; therefore autoantibody screening among high-risk subgroups may be useful for clinicians to determine whether prenatal thyroid treatment is warranted

Toxoplasma gondii IgG Associations with Sleepwake Problems, Sleep Duration and Timing

Background: Evidence links Toxoplasma gondii (T. gondii), a neurotropic parasite, with schizophrenia, mood disorders and suicidal behavior, all of which are associated and exacerbated by disrupted sleep. Moreover, low-grade immune activation and dopaminergic overstimulation, which are consequences of T. gondii infection, could alter sleep patterns and duration. Methods: Sleep data on 833 Amish participants [mean age (SD) = 44.28 (16.99) years; 59.06% women] were obtained via self-reported questionnaires that assessed sleep problems, duration and timing. T. gondii IgG was measured with ELISA. Data were analyzed using multivariable logistic regressions and linear mixed models, with adjustment for age, sex and family structure. Results: T. gondii seropositives reported less sleep problems (p \u3c 0.005) and less daytime problems due to poor sleep (p \u3c 0.005). Higher T. gondii titers were associated with longer sleep duration (p \u3c 0.05), earlier bedtime (p \u3c 0.005) and earlier mid-sleep time (p \u3c 0.05). Conclusions: It seems unlikely that sleep mediates the previously reported associations between T. gondii and mental illness. Future longitudinal studies with objective measures are necessary to replicate our findings

Enteric dysbiosis and fecal calprotectin expression in premature infants.

BackgroundPremature infants often develop enteric dysbiosis with a preponderance of Gammaproteobacteria, which has been related to adverse clinical outcomes. We investigated the relationship between increasing fecal Gammaproteobacteria and mucosal inflammation, measured by fecal calprotectin (FC).MethodsStool samples were collected from very-low-birth weight (VLBW) infants at ≤2, 3, and 4 weeks' postnatal age. Fecal microbiome was surveyed using polymerase chain reaction amplification of the V4 region of 16S ribosomal RNA, and FC was measured by enzyme immunoassay.ResultsWe enrolled 45 VLBW infants (gestation 27.9 ± 2.2 weeks, birth weight 1126 ± 208 g) and obtained stool samples at 9.9 ± 3, 20.7 ± 4.1, and 29.4 ± 4.9 days. FC was positively correlated with the genus Klebsiella (r = 0.207, p = 0.034) and its dominant amplicon sequence variant (r = 0.290, p = 0.003), but not with the relative abundance of total Gammaproteobacteria. Klebsiella colonized the gut in two distinct patterns: some infants started with low Klebsiella abundance and gained these bacteria over time, whereas others began with very high Klebsiella abundance.ConclusionIn premature infants, FC correlated with relative abundance of a specific pathobiont, Klebsiella, and not with that of the class Gammaproteobacteria. These findings indicate a need to define dysbiosis at genera or higher levels of resolution

The effects of eye and head X-irradiation on recurrent herpes simplex ocular infection in rabbits

Thesis (M.A.)--Boston UniversityPLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at [email protected]. Thank you.Eighty Four rabbits were studied over a period of 2 years for the effects of eye and head X-irradiation on their latent herres simplex ocular infection. Animals were infected intraocularly with herpes simplex virus and allowed to recover from the resultant keratitis. After the latency of the virus was established through daily culture of the eyes of the rabbits, the animals were irradiated. Irradiation was followed by periods of daily culture of both eyes. Eye irradiation of 200, 400, 1200, and 2890 roentgens produce no significant reactivation of the virus in the irradiated eye. On the other hand, head irradiation of 3000 roentgens produced recurrence of the virus in the eyes in a high percentage of the treated rabbits. This effect was reproduced repeatedly. Further experiments seemed to suggest that the virus was latent in the brain and could be reactivated in situ by X-irradiation of the brain. The infectious viral particles appeared to move preferentially to the site of initial infection, This effect may have importance in the fields of clinical medicine, radiation therapy and radiology, and in space travel safety parameters. Further research is planned.2031-01-0

The Association Between Variants on Chromosome 9p21 and Inflammatory Biomarkers in Ethnically Diverse Women With Coronary Heart Disease: A Pilot Study

Background: The most consistently replicated genetic variants associated with coronary heart disease (CHD) in populations of European descent have been found on chromosome 9p21. Yet there is little known about these associations in ethnic groups of African ancestry. These disease-associated variants are located in a genomic region of unknown function. The purpose of this exploratory study was to examine the allelic frequencies and haplotype structure of single nucleotide polymorphisms (SNPs) for Black and White women with CHD. The authors also sought to explore the relationship between these genetic variants and biomarkers of inflammation. Methods: Using polymerase chain reaction amplification, the authors genotyped 8 SNPs in a 58-kilobase region of chromosome 9p21 in a cohort of women with CHD (n = 91). The authors examined the interethnic relationship between the SNPs and four inflammatory biomarkers (C-reactive protein, intercellular adhesion molecule-1, interleukin-6, and tumor necrosis factor-alpha) using analysis of variance (ANOVA). Results: We found considerable interethnic allelic and haplotype diversity across the 9p21 locus, with only two SNPs in perfect linkage disequilibrium (LD) in both races. A pair of high- and low-risk haplotypes was most common in White women, while about 41% of Blacks carried the risk alleles for three of the eight SNPs the authors examined. The interethnic associations between the SNP genotypes and inflammatory markers were divergent in both direction and magnitude. Conclusions: Our results lend support for the importance of ancestry-specific allelic context when examining variants on chromosome 9p21. Additional work is needed to elucidate the genetic contribution to inflammatory biomarkers for diverse racial groups