Background: Preterm birth is a major determinant of neonatal survival and morbidity, but the gut microbiome and associated enteric inflammation are also key factors in neonatal development and the risk of associated morbidities. We prospectively and longitudinally followed two cohorts of preterm infants, one of which was fed activated Bifidobacterium longum subsp. infantis (B. infantis) EVC001 8 × 109 CFU daily, and the other was not fed a probiotic. Hospital feeding protocol assigned all infants born at <1500 g and/or < 32 weeks corrected gestational age to the probiotic feeding protocol, whereas infants born at >1500 g and/or >32 weeks corrected gestational age were not fed a probiotic. Fecal samples were opportunistically collected from 77 infants throughout the hospital stay, and subjected to shotgun metagenomic sequencing and quantification of enteric inflammation. De-identified metadata was collected from patient medical records.Results: The gut microbiome of preterm infants was typified by a high abundance of Enterobacteriaceae and/or Staphylococcaceae, and multivariate modeling identified the probiotic intervention, rather than degree of prematurity, day of life, or other clinical interventions, as the primary source of change in the gut microbiome. Among infants fed B. infantis EVC001, a high abundance of total Bifidobacteriaceae developed rapidly, the majority of which was B. infantis confirmed via subspecies-specific qPCR. Associated with this higher abundance of Bifidobacteriaceae, we found increased functional capacity for utilization of human milk oligosaccharides (HMOs), as well as reduced abundance of antibiotic resistance genes (ARGs) and the taxa that harbored them. Importantly, we found that infants fed B. infantis EVC001 exhibited diminished enteric inflammation, even when other clinical variables were accounted for using multivariate modeling.Conclusion: These results provide an important observational background for probiotic use in a NICU setting, and describe the clinical, physiological, and microbiome-associated improvements in preterm infants associated with B. infantis EVC001 feeding.

Abstract, Tissue and plasma concentrations of several cytokines are increased in patients with inflammatory bowel disease (IBD). Platelets play an important role in inflammation and circulate in an activated state in patients with IBD. This study assesses the expression of IL-8 and IL-1 receptors on the surface of platelets from patients with IBD using phycoerythrin (PE)-labelled recombinant human rhIL-lp and rhIL-8 and flow cytometry. The percentage IL-1R expressing platelets (median and interquartile range IQR) in the IBD group was 8.7% (5.5-18.2) compared to 4.2% (2.3-6.1) in controls (P = 0.02). The percentage IL-8R expressing platelets in the IBD group was 22.5% (16.5-27.9) and 9.2% (4.3-9.6) in controls ( P < 0.001). Furthermore, platelet IL-1R expression in patients with IBD was inversely related to the total daily dose of steroids ( r = -0.71, P < 0.01 linear regression analysis). Finally, platelet rich plasma from healthy controls was stimulated with rhIL-lp and rhIL-8 and assessed for activation dependent expression of platelet aGPIIb/IIIa and CD62 (pselectin, GMP-140). IL-IP and IL-8 in vitro significantly and specifically activated the platelets. The surface membrane of platelets is able to express functional IL-1R and IL-8R, the expression of which is signficantly increased in IBD. Interleukinl p and IL-8 modulate platelet activation in vitro indicating a target role for platelet function in inflammation.

In this pilot study the increased inbreeding in the cases, lack of likely sampling bias, the increased frequency of T2D in Burmese, and small number of breed founders are consistent with the involvement of a major locus in diabetes in Burmese cats with a significant risk allele prevalence. However, low case numbers meant this could not be unambiguously confirmed. A genome-wide association study may be useful for investigating the genetic cause of T2D.

BackgroundPreterm birth is a major determinant of neonatal survival and morbidity, but the gut microbiome and associated enteric inflammation are also key factors in neonatal development and the risk of associated morbidities. We prospectively and longitudinally followed two cohorts of preterm infants, one of which was fed Bifidobacterium longum subsp. infantis (B. infantis) EVC001 daily, and the other was not fed a probiotic. Hospital feeding protocol assigned all infants born at less than 1500g and/or 34 weeks corrected gestational age to the probiotic feeding protocol, whereas infants born at > 1500g and/or 34 weeks corrected gestational age were not fed a probiotic. Fecal samples collected opportunistically (approximately 2 samples per week) throughout the hospital stay were analyzed from 292 samples collected from 77 infants. Fecal samples were subjected to shotgun metagenomic sequencing and quantification of enteric inflammation markers. We also collected de-identified metadata from patient medical records.ResultsThe gut microbiome of preterm infants was typified by a high abundance of Enterobacteriaceae and/or Staphylococcaceae and multivariate modeling identified the probiotic intervention, rather than degree of prematurity, day of life, or other clinical interventions as the primary source of change in the gut microbiome. Among infants fed B. infantis EVC001, a high abundance of total Bifidobacteriaceae developed rapidly, the majority of which was B. infantis confirmed via subspecies-specific qPCR. Associated with this higher abundance of Bifidobacteriaceae, we found increased functional capacity for utilization of human milk oligosaccharides (HMOs), as well as reduced abundance of antibiotic resistance genes (ARGs) and the taxa that harbored them. Importantly, we found that infants fed B. infantis EVC001 experienced diminished enteric inflammation, even when other clinical variables were accounted for using multivariate modeling.ConclusionThese results provide an important observational background for probiotic use in a NICU setting, and describe the clinical, physiological, and microbiome-associated improvements in preterm infants associated with B. infantis EVC001 feeding.

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