Routine ultrasound screening for vasa previa using American Institute of Ultrasound in Medicine criteria will almost universally lead to good outcomes and prevent perinatal mortality.

Fungal and bacterial commensal organisms play a complex role in the health of the human host. Expansion of commensal ecology after birth is a critical period in human immune development. However, the initial fungal colonization of the primordial gut remains undescribed. To investigate primordial fungal ecology, we performed amplicon sequencing and culture‐based techniques of first‐pass meconium, which forms in the intestine prior to birth, from a prospective observational cohort of term and preterm newborns. Here, we describe fungal ecologies in the primordial gut that develop complexity with advancing gestational age at birth. Our findings suggest homeostasis of fungal commensals may represent an important aspect of human biology present even before birth. Unlike bacterial communities that gradually develop complexity, the domination of the fungal communities of some preterm infants by Saccromycetes, specifically Candida, may suggest a pathologic association with preterm birth.—Willis, K. A., Purvis, J. H., Myers, E. D., Aziz, M. M., Karabayir, I., Gomes, C. K., Peters, B. M., Akbilgic, O., Talati, A. J., Pierre, J. F. Fungi form interkingdom microbial communities in the primordial human gut that develop with gestational age. FASEB J. 33, 12825–12837 (2019). http://www.fasebj.org

During the newborn period, intestinal commensal bacteria influence pulmonary mucosal immunology via the gut-lung axis. Epidemiological studies have linked perinatal antibiotic exposure in human newborns to an increased risk for bronchopulmonary dysplasia, but whether this effect is mediated by the gut-lung axis is unknown. To explore antibiotic disruption of the newborn gut-lung axis, we studied how perinatal maternal antibiotic exposure influenced lung injury in a hyperoxia-based mouse model of bronchopulmonary dysplasia. We report that disruption of intestinal commensal colonization during the perinatal period promotes a more severe bronchopulmonary dysplasia phenotype characterized by increased mortality and pulmonary fibrosis. Mechanistically, metagenomic shifts were associated with decreased IL-22 expression in bronchoalveolar lavage and were independent of hyperoxia-induced inflammasome activation. Collectively, these results demonstrate a previously unrecognized influence of the gut-lung axis during the development of neonatal lung injury, which could be leveraged to ameliorate the most severe and persistent pulmonary complication of preterm birth.

Objectives To examine the association between six-minute walk test (6 MWT) performance and all-cause mortality, coronary heart disease mortality, and incident coronary heart disease in older adults. Methods We conducted a time-to-event analysis of 1,665 Cardiovascular Health Study participants with a 6 MWT and without prevalent cardiovascular disease. Results During a mean follow-up of 8 years, there were 305 incident coronary heart disease events, 504 deaths of which 100 were coronary heart disease-related deaths. The 6 MWT performance in the shortest two distance quintiles was associated with increased risk of all-cause mortality (290-338 meters: HR 1.7; 95% CI, 1.2-2.5; <290 meters: HR 2.1; 95% CI, 1.4-3.0). The adjusted risk of coronary heart disease mortality incident events among those with a 6 MWT <290 meters was not significant. Discussion Performance on the 6 MWT is independently associated with all-cause mortality and is of prognostic utility in community-dwelling older adults.

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25Fungal and bacterial commensal organisms play a complex role in the health of the human host. 26Expansion of commensal ecology after birth is a critical period in human immune development. 27However, the initial fungal colonization of the primordial gut remains undescribed. To investigate 28 primordial fungal ecology, we performed amplicon sequencing and culture-based techniques of first-29 pass meconium, which forms in the fetal intestine prior to birth, from a prospective observational 30 cohort of term-born and preterm newborns. Here, we describe fungal ecologies in the primordial gut 31 that develop complexity with advancing gestational age at birth. Our findings suggest homeostasis of 32 fungal commensals may represent an important aspect of human biology present even before birth. 33Unlike bacterial communities which gradually develop complexity, the domination of the fungal 34 communities of some preterm infants by Saccromycetes, specifically Candida, may suggest a 35 pathologic association with preterm birth.36 37 38 39 42 colonize our barrier surfaces, such as the intestinal tract. The human gut microbiome is host to a 43 complex interkingdom ecology of bacteria, fungi, archaea, protozoa and viruses. While recent 44 research has led to a drastic expansion in our understanding of bacterial communities in the gut 1-4 , 45 little is known about the role of fungal organisms, collectively the mycobiome, particularly in relation to 46 their impact on the population dynamics of early-life colonization. 47 48 The tightly choreographed maturation of commensal microbial communities is crucial to mammalian 49 immune development 5 . Fungal organisms can form a crucial nidus for initial colonization 6 and may 50 play a vital role in facilitating early colonization of the neonatal gut. Disruption of this process could 51 produce pathogenic fungal overgrowth or invasive disease. Indeed, this mechanism may play a role in 52 the development of asthma and other metabolic and immunological diseases 7 . The intestinal 53 mycobiota likely confers unique physiologic effects to the host, in part by processing nutrients and 54 vitamins either separately or in conjunction with the microbiome. However, characterization of the 55 functional impact of early mycobiome is impaired by limited knowledge of the normal development of 56 these communities. To understand the functional impact of the early-life mycobiome on human health, 57 it is necessary to determine if the human primordial gut hosts fungal communities, if these 58 communities are established before or after birth and if the presence of fungi in the early gut impacts 59 neonatal physiology. 61Advances in next-generation sequencing techniques have pushed back the timing of initial 62 commensal colonization 3 which was initially thought to occur at birth 8,9 . Despite these advances, 63 interkingdom interactions within microbial communities and the influence of environmental factors on 64 the dynamics of microbial ecosystems remains poorly understood. Due to delayed prog...