Impact of probiotics on gut microbiome of extremely preterm or extremely low birthweight infants

\ua9 The Author(s) 2024.Impact: Meta-analysis of probiotic administration to very preterm or very low birthweight (VP/VLBW) infants shows reduced risk of necrotising enterocolitis (NEC). Separately reported outcomes for extremely preterm infants (<28 weeks) or extremely low birth weight infants (<1000 g) (EP/ELBW) are lacking meaning some clinicians do not administer probiotics to EP/ELBW infants despite their high risk of NEC. We present data showing the gut microbiome is impacted in EP/ELBW infants in a similar manner to VP/VLBW infants, suggesting that risk reduction for necrotising enterocolitis that is microbiome driven will also be seen in EP/ELBW infants, making probiotic administration beneficial

Protocol to study the inter-relationship between phageome and lipidome in low-volume preterm milk

\ua9 2025 The AuthorsBacteriophages and lipids in human milk may benefit preterm infant health by modulating gut microbiomes. Here, we present a protocol for analyzing the phageome and lipidome in preterm milk using shotgun metagenomics and untargeted lipidomics approaches, respectively. We describe steps for extracting phages and lipids in low-volume milk, characterizing phageome using an in-house bioinformatic pipeline, and statistical analysis to correlate the phageome and lipidome. Finally, we detail an in vitro assay to examine the associations between fatty acid chain length and phage morphotype. For complete details on the use and execution of this protocol, please refer to Yew et al.

Increased circulating ANG II and TNF-α represents important risk factors in obese Saudi adults with hypertension irrespective of diabetic status and BMI

Central adiposity is a significant determinant of obesity-related hypertension risk, which may arise due to the pathogenic inflammatory nature of the abdominal fat depot. However, the influence of pro-inflammatory adipokines on blood pressure in the obese hypertensive phenotype has not been well established in Saudi subjects. As such, our study investigated whether inflammatory factors may represent useful biomarkers to delineate hypertension risk in a Saudi cohort with and without hypertension and/or diabetes mellitus type 2 (DMT2). Subjects were subdivided into four groups: healthy lean controls (age: 47.9±5.1 yr; BMI: 22.9±2.1 Kg/m2), non-hypertensive obese (age: 46.1±5.0 yr; BMI: 33.7±4.2 Kg/m2), hypertensive obese (age: 48.6±6.1 yr; BMI: 36.5±7.7 Kg/m2) and hypertensive obese with DMT2 (age: 50.8±6.0 yr; BMI: 35.3±6.7 Kg/m2). Anthropometric data were collected from all subjects and fasting blood samples were utilized for biochemical analysis. Serum angiotensin II (ANG II) levels were elevated in hypertensive obese (p<0.05) and hypertensive obese with DMT2 (p<0.001) compared with normotensive controls. Systolic blood pressure was positively associated with BMI (p<0.001), glucose (p<0.001), insulin (p<0.05), HOMA-IR (p<0.001), leptin (p<0.01), TNF-α (p<0.001) and ANG II (p<0.05). Associations between ANG II and TNF-α with systolic blood pressure remained significant after controlling for BMI. Additionally CRP (p<0.05), leptin (p<0.001) and leptin/adiponectin ratio (p<0.001) were also significantly associated with the hypertension phenotype. In conclusion our data suggests that circulating pro-inflammatory adipokines, particularly ANG II and, TNF-α, represent important factors associated with a hypertension phenotype and may directly contribute to predicting and exacerbating hypertension risk

Gut microbiome in paediatric short bowel syndrome: a systematic review and sequencing re-analysis

\ua9 The Author(s) 2025.Impact: Children with short bowel syndrome depend on parenteral nutrition, which carries significant risks. Short bowel syndrome patients show reduced gut microbial diversity, increased inflammation-associated bacteria, and fewer beneficial bacteria. This is the first systematic review and meta-analysis examining the gut microbiome in children with short bowel syndrome. The review demonstrated significantly lower bacterial diversity and richness in children with short bowel syndrome, regardless of achievement of intestinal autonomy. Diversity and richness were greater in children who achieved intestinal autonomy than those on parenteral nutrition, though not statistically significant. Larger studies adjusting for confounding factors may identify future therapeutic strategies

Analyzing Childlessness

Childlessness has been on the rise in many European societies. In Germany, the UK, Austria, the Netherlands, and Switzerland, childlessness has increased starting with the 1950s cohorts. In these countries, about 20 % of the women born around 1965 will remain childless. In southern Europe and the former state-socialist countries of Central and Eastern Europe, the rise in levels of childlessness is a more recent phenomenon. Yet among younger cohorts in these countries, childlessness has reached levels of 15 % or higher. In this introductory chapter, we summarize the long-term trends in childlessness and discuss the differences between European countries in the prevalence of childlessness. We also outline the structure and the logic of this volume

Characterising the metabolic functionality of the preterm neonatal gut microbiome prior to the onset of necrotising enterocolitis: a pilot study

\ua9 The Author(s) 2024. Background: Necrotising enterocolitis (NEC) is a devastating bowel disease that primarily occurs in infants born prematurely and is associated with abnormal gut microbiome development. While gut microbiome compositions associated with NEC have been well studied, there is a lack of experimental work investigating microbiota functions and their associations with disease onset. The aim of this pilot study was to characterise the metabolic functionality of the preterm gut microbiome prior to the onset of NEC compared with healthy controls. Results: Eight NEC infants were selected of median gestation 26.5 weeks and median day of life (DOL) of NEC onset 20, with one sample used per infant, collected within one to eight days (median four) before NEC onset. Each NEC case was matched to a control infant based on gestation and sample DOL, the main driver of microbiome composition in this population, giving a total cohort of 16 infants for this study. Dietary exposures were well matched. The microbiota of NEC and control infants showed similar wide-ranging metabolic functionalities. All 94 carbon sources were utilised to varying extents but NEC and control samples clustered separately by supervised ordination based on carbon source utilisation profiles. For a subset of eight samples (four NEC, four control) for which pre-existing metagenome data was available, microbiome composition was found to correlate significantly with metabolic activity measured on Biolog plates (p = 0.035). Comparisons across all 16 samples showed the NEC microbiota to have greater utilisation of carbon sources that are the products of proteolytic fermentation, specifically amino acids. In pairwise comparisons, L-methionine was highly utilised in NEC samples, but poorly utilised in controls (p = 0.043). Carbon sources identified as discriminatory for NEC also showed a greater enrichment for established markers of inflammatory disease, such as inflammatory bowel disease, irritable bowel syndrome and diverticular disease. Conclusions: Before NEC onset, the preterm gut microbiota showed greater metabolic utilisation of amino acids, potentially indicating a shift from predominantly saccharolytic to proteolytic fermentation. Products of amino acid breakdown could therefore act as biomarkers for NEC development. A larger study is warranted, ideally with infants from multiple sites

Lymphocyte subsets in human immunodeficiency virus-unexposed Brazilian individuals from birth to adulthood

Ethnic origin, genetics, gender and environmental factors have been shown to influence some immunologic indices, so that development of reference values for populations of different backgrounds may be necessary. We have determined the distribution of lymphocyte subsets in healthy Brazilian individuals from birth to adulthood. Lymphocyte subsets were determined using four-colour cytometry in a cross-sectional study of 463 human immunodeficiency virus-unexposed children and adults from birth through 49 years of age. Lymphocyte subsets varied according to age, as previously observed in other studies. However, total CD4+ T cell numbers were lower than what was described in the Pediatric AIDS Clinical Trials Group P1009 (PACTG P1009), which assessed an American population of predominantly African and Hispanic backgrounds until the 12-18 year age range, when values were comparable. Naïve percentages and absolute values of CD8+ T cells, as assessed by CD45RA expression, were also lower than the PACTG P1009 data for all analysed age ranges. CD38 expression on both CD4+ and CD8+ T cells was lower than the PACTG P1009 values, with a widening gap between the two studies at older age ranges. Different patterns of cell differentiation seem to occur in different settings and may have characteristic expression within each population.Universidade Federal de São Paulo (UNIFESP) Departamento de MedicinaCentro Assistencial Cruz de MaltaUniversidade Federal de São Paulo (UNIFESP) Departamento de PediatriaUNIFESP, Depto. de MedicinaUNIFESP, Depto. de PediatriaSciEL

The core phageome and its interrelationship with preterm human milk lipids

\ua9 2023 The AuthorsPhages and lipids in human milk (HM) may benefit preterm infant health by preventing gastrointestinal pathobiont overgrowth and microbiome modulation. Lipid association may promote vertical transmission of phages to the infant. Despite this, interrelationships between lipids and phages are poorly characterized in preterm HM. Shotgun metagenomics and untargeted lipidomics of phage and lipid profiles from 99 preterm HM samples reveals that phages are abundant and prevalent from the first week and throughout the first 100 days of lactation. Phage-host richness of preterm HM increases longitudinally. Core phage communities characterized by Staphylococcus- and Propionibacterium-infecting phages are significantly correlated with long-chain fatty acid abundances over lactational age. We report here a phage-lipid interaction in preterm HM, highlighting the potential importance of phage carriage in preterm HM. These results reveal possible strategies for phage carriage in HM and their importance in early-life microbiota development

Gut microbiota and intestinal rehabilitation: A prospective childhood cohort longitudinal study of short bowel syndrome (the MIRACLS study): Study protocol

\ua9 Author(s) (or their employer(s)) 2024.Introduction Short bowel syndrome (SBS) is the predominant cause of paediatric intestinal failure. Although life-saving, parenteral nutrition (PN) is linked to complications and may impact quality of life (QoL). Most children will experience intestinal rehabilitation (IR), but the mechanisms underpinning this remain to be understood. SBS is characterised by abnormal microbiome patterns, which might serve as predictive indicators for IR. We aim to characterise the microbiome profiles of children with SBS during IR, concurrently exploring how parental perspectives of QoL relate to IR. Methods and analysis This study will enrol a minimum of 20 paediatric patients with SBS (0-18 years). Clinical data and biological samples will be collected over a 2-year study period. We will apply 16S rRNA gene sequencing to analyse the microbiome from faecal and gut tissue samples, with additional shotgun metagenomic sequencing specifically on samples obtained around the time of IR. Gas chromatography with flame ionisation detection will profile faecal short-chain fatty acids. Plasma citrulline and urinary intestinal fatty acid binding proteins will be measured annually. We will explore microbiome-clinical covariate interactions. Furthermore, we plan to assess parental perspectives on QoL during PN and post-IR by inviting parents to complete the Paediatric Quality of Life questionnaire at recruitment and after the completion of IR. Ethics and dissemination Ethical approval was obtained from the East Midlands-Nottingham 2 Research Ethics Committee (22/EM/0233; 28 November 2022). Recruitment began in February 2023. Outcomes of the study will be published in peer-reviewed scientific journals and presented at scientific meetings. A lay summary of the results will be made available to participants and the public. Trial registration number ISRCTN90620576

Fertility Ideals of Women and Men Across the Life Course

This paper explores the stability of women’s and men’s fertility preferences across the life course. The data come from the first six waves of the German Family Panel (pairfam), which span the period from 2008/2009 until 2013/2014. In our analysis, fertility preferences are measured using the following question: “Under ideal circumstances, how many children would you like to have?” The average number cited by both women and men is 2.2. With rising age, this number declines modestly. Relying on fixed-effects modelling, we find that neither partnership status nor economic circumstances have any causal effect on fertility preferences. However, as the number of children a respondent has increases, his or her ideal number of children is also likely to grow. Thus, fertility ideals appear to undergo changes over time, and are adjusted in line with the size of the respondent’s own family