Background Premature infants have a high risk for dysbiosis of the gut microbiome. Mother’s own breastmilk (MOM) has been found to favorably alter gut microbiome composition in infants born at term. Evidence about the influence of feeding type on gut microbial colonization of preterm infants is limited. Objective The purpose of this study was to explore the effect of feeding types on gut microbial colonization of preterm infants in the neonatal intensive care unit (NICU). Methods Thirty-three stable preterm infants were recruited at birth and followed-up for the first 30 days of life. Daily feeding information was used to classify infants into six groups (mother’s own milk [MOM], human donated milk [HDM], formula, MOM+HDM, MOM+Formula, and HDM+forumla) during postnatal days 0–10, 11–20, and 21–30 after birth. Stool samples were collected daily. DNA extracted from stool was used to sequence the 16S rRNA gene. Exploratory data analysis was conducted with a focus on temporal changes of microbial patterns and diversities among infants from different feeding cohorts. Prediction of gut microbial diversity from feeding type was estimated using linear mixed models. Results Preterm infants fed MOM (at least 70% of the total diet) had highest abundance of Clostridiales, Lactobacillales, and Bacillales compared to infants in other feeding groups, whereas infants fed primarily human donor milk or formula had a high abundance of Enterobacteriales compared to infants fed MOM. After controlling for gender, postnatal age, weight and birth gestational age, the diversity of gut microbiome increased over time and was constantly higher in infants fed MOM relative to infants with other feeding types (p < .01). Discussion Mother’s own breast milk benefits gut microbiome development of preterm infants, including balanced microbial community pattern and increased microbial diversity in early life.

Gut microbiota plays a key role in multiple aspects of human health and disease, particularly in early life. Distortions of the gut microbiota have been found to correlate with fatal diseases in preterm infants, however, developmental patterns of gut microbiome and factors affecting the colonization progress in preterm infants remain unclear. The purpose of this prospective longitudinal study was to explore day-to-day gut microbiome patterns in preterm infants during their first 30 days of life in the neonatal intensive care unit (NICU) and investigate potential factors related to the development of the infant gut microbiome. A total of 378 stool samples were collected daily from 29 stable/healthy preterm infants. DNA extracted from stool was used to sequence the V4 region of the 16S rRNA gene region for community analysis. Operational taxonomic units (OTUs) and α-diversity of the community were determined using QIIME software. Proteobacteria was the most abundant phylum, accounting for 54.3% of the total reads. Result showed shift patterns of increasing Clostridium and Bacteroides, and decreasing Staphylococcus and Haemophilus over time during early life. Alpha-diversity significantly increased daily in preterm infants after birth and linear mixed-effects models showed that postnatal days, feeding types and gender were associated with the α-diversity, p< 0.05–0.01. Male infants were found to begin with a low α-diversity, whereas females tended to have a higher diversity shortly after birth. Female infants were more likely to have higher abundance of Clostridiates, and lower abundance of Enterobacteriales than males during early life. Infants fed mother’s own breastmilk (MBM) had a higher diversity of gut microbiome and significantly higher abundance in Clostridiales and Lactobacillales than infants fed non-MBM. Permanova also showed that bacterial compositions were different between males and females and between MBM and non-MBM feeding types. In conclusion, infant postnatal age, gender and feeding type significantly contribute to the dynamic development of the gut microbiome in preterm infants.

Background Vulnerable preterm infants experience repeated and prolonged pain/stress stimulation during a critical period in their development while in the neonatal intensive care unit (NICU). The contribution of cumulative pain/stressors to altered neurodevelopment remains unclear. The study purpose was to investigate the impact of early life painful/stressful experiences on neurobehavioral outcomes of preterm infants in the NICU. Methods A prospective exploratory study was conducted with fifty preterm infants (28 0/7 – 32 6/7 weeks gestational age) recruited at birth and followed for four weeks. Cumulative pain/stressors (NICU Infant Stressor Scale) were measured daily and neurodevelopmental outcomes (NICU Network Neurobehavioral Scale) were examined at 36-37 weeks post-menstrual age. Data analyses were conducted on the distribution of pain/stressors experienced over time and the linkages among pain/stressors and neurobehavioral outcomes. Results Preterm infants experienced a high degree of pain/stressors in the NICU, both in numbers of daily acute events (22.97±2.30 procedures) and cumulative times of chronic/stressful exposure (42.59±15.02 hours). Both acute and chronic pain/stress experienced during early life significantly contributed to the neurobehavioral outcomes, particularly in stress/abstinence (p < 0.05) and habituation responses (p < 0.01), meanwhile, direct breastfeeding and skin-to-skin holding were also significantly associated with habituation (p < 0.01 – 0.05). Conclusion Understanding mechanisms by which early life experience alters neurodevelopment will assist clinicians in developing targeted neuroprotective strategies and individualized interventions to improve infant developmental outcomes.

SYNOPSIS Neonates may experience more than 300 painful procedures and surgeries throughout their hospitalization. Prior to 1980, there was a longstanding misconception that neonates do not experience pain. Current studies demonstrate that not only do neonate’s experience pain, but due to their immature nervous systems, they are hypersensitive to painful stimuli. Poorly treated pain during the neonatal period may lead to negative long-term consequences. Proper assessment of a neonate’s pain is vital. Standardized pain scales allow for consistency between providers and individualized treatment plans for neonates. The use of non-pharmacological treatments such as, nonnutritive sucking, facilitated tucking, kangaroo care, swaddling and heel warming may all be beneficial in alleviating a neonate’s pain. Pharmacological treatments in the neonate have been well established and may include, but are not limited to opioids and non-opioid analgesics. Pharmacological and non-pharmacological interventions can be used in conjunction with each other to increase the efficacy of analgesia.

The prevalence of breastfeeding at 6 months for preterm infants in this sample was low. Strategies to improve breastfeeding duration for preterm infants are needed, including support and education of mothers while in the hospital.

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Intestinal organoids are multicellular crypt-like structures that can be derived from adult intestinal stem cells (ISCs), embryonic stem cells (ESCs) or induced pluripotent stem cells (IPSCs). Here we show that intestinal organoids generated from mouse ESCs were enriched in ISCs and early progenitors. Treatment of these organoids with a γ-secretase inhibitor increased Math1 and decreased Hes1 expression, indicating Notch signaling regulates ISC differentiation in these organoids. Lgr5 and Tert positive ISCs constituted approximately 10% and 20% of the organoids. As found in native tissue, Lgr5 and Tert expressing cells resolved into two discreet populations, which were stable over time. Intestinal organoids derived from cancer-prone Apc(Min/+) mice showed similar numbers of ISCs, but had reduced Math1 expression, indicating a suppressed secretory cell differentiation potential (as found in intestinal tissue). Apc(Min/+) organoids were used to screen epigenetically active compounds for those that increased Math1 expression and organoid differentiation (including HDAC inhibitors, Sirtuin (SIRT) modulators and methyltransferase inhibitors). Broad-spectrum HDAC inhibitors increased both Math1 and Muc2 expression, indicating an ability to promote the suppressed secretory cell differentiation pathway. Other epigenetic compounds had a diverse impact on cell differentiation, with a strong negative correlation between those that activated the secretory marker Muc2 and those that activated the absorptive cell marker Fabp2. These data show that ESC-derived intestinal organoids can be derived in large numbers, contain distinct ISC types and can be used to screen for agents that promote cell differentiation through different lineage pathways.

Post inflammatory irritable bowel syndrome (PI-IBS), a subset of IBS, is characterized by symptoms of visceral pain, bloating, and changed bowel habits that occur post initial episode of intestinal infection. Gut microbial dysbiosis or inflammation plays a key role in the pathogenesis of abdominal hypersensitivity of PI-IBS. Electroacupuncture (EA) stimulation results in an alleviated PI-IBS-associated symptom. This study investigated the effect of EA on IL-18 and gut microbial dysbiosis in one visceral hypersensitive rat models with PI-IBS. A trinitrobenzene sulfonic acid (TNBS)-induced visceral hypersensitivity rat model was developed. EA stimulation was applied to the ST25 and ST36 acupoints. Animals were assessed using abdominal withdrawal reflex (AWR) scores to determine the development of colonic visceral hypersensitivity. The 16S rRNA was used to correlate microbial diversity. IL-18 expression in colon was quantified by quantitative real-time PCR and western blotting. We identified that model rats had an increased visceral hypersensitivity to colorectal distention at different distention pressures compared with the normal group. Sensitivity to colorectal distention decreased after EA stimulation. The composition of the fecal microbiota was different between groups. Specifically, in the model group Empedobacter, Psychrobacter, Enterococcus, Butyricimonas, Vampirovibrio, Kurthia, Intestinimonas, Neisseria, Falsiporphyromonas, Bilophila, Fusobacterium, Alistipes, Veillonella, Flavonifractor, Clostridium XlVa were more abundant affected genera, whereas Lactobacillus was enriched in normal rats. EA stimulation was correlated with significant decrease in the phyla of Fusobacteria. The mRNA and protein levels of IL-18 were higher in the model group. Meanwhile, EA stimulation attenuated this response. In a word, our findings suggest that PI-IBS is associated with significant increase in IL-18 levels as well as an alteration in microbiome diversity. These changes can be reversed with EA treatment. EA stimulation has a positive effect in alleviating symptoms of visceral hypersensitivity and protecting the gastrointestinal tract.