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OBJECTIVES: To test the utility of various biomarkers as indicators of gut dysfunction in cystic fibrosis (CF) and determine whether intraindividual variations in these measures are repeatable over short intervals and whether interindividual variations correlate with clinical outcomes. STUDY DESIGN: We performed a cross-sectional, limited longitudinal study of children with CF aged 1-21 years who provided blood and stool samples at 2 or 3 visits, 2 weeks and 3 months apart, which were assayed for markers of intestinal inflammation (fecal calprotectin [fCal], lipocalin-2 [fLcn2], neopterin), and permeability (plasma lipopolysaccharide [LPS] antibodies, LPS-binding protein) by enzyme immunoassays. Control specimens were obtained from children without CF who had undergone esophagogastroduodenoscopy and had no evidence of gut inflammation. RESULTS: Twenty-six of 29 participants with CF completed the study. Sixty-nine stools (57 case/12 control) and 76 plasmas (60 case/16 control) were analyzed. LPS antibody had reliable intraindividual stability. fCal, fLcn2, and neopterin were significantly greater in CF than in control samples. fCal was negatively correlated with 3-month interval change (Δ) in weight-for-age z-score, body mass index/weight-for-length z-score, and forced expiratory volume in 1 second. fLcn2 was negatively correlated with FEV1 but not with anthropometrics. No marker correlated with Δbody mass index/weight-for-length z-score or ΔFEV1. CONCLUSIONS: fLcn2 is elevated in people with CF and might predict worse interval pulmonary function. Expanded studies are warranted to test if fLcn2 correlates with changes in additional outcomes.
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Fibrose Cística , Criança , Humanos , Fibrose Cística/complicações , Fibrose Cística/metabolismo , Estudos Longitudinais , Neopterina , Estudos Transversais , Lipopolissacarídeos , Inflamação/metabolismo , AnticorposRESUMO
BACKGROUND: A subset of patients with serology suggesting celiac disease have an initially negative biopsy but subsequently develop histopathologic celiac disease. Here we characterize patients with potential celiac disease who progress to celiac disease. METHODS: We performed a retrospective analysis of children (0-18 years of age) with biopsy-confirmed celiac disease seen at St. Louis Children's Hospital between 2013 and 2018. RESULTS: Three hundred sixteen of 327 (96%) children with biopsy-confirmed celiac disease were diagnosed on initial biopsy. The 11 children with potential celiac disease who progressed to celiac disease had lower anti-tissue transglutaminase (anti-TTG IgA) concentrations (2.4 (1.6-5) X upper limit of normal (ULN) vs. 6.41 (3.4-10.5) X ULN) at time of first biopsy. Their median anti-TTG IgA concentrations rose from 2.4 (1.6-5) X ULN to 3.6 (3.1-9.2) X ULN between biopsies. CONCLUSIONS: Four percent of biopsy confirmed celiac patients initially had a negative biopsy, but later developed histopathologic celiac disease. This is likely an underestimate as no surveillance algorithm was in place. We recommend repeat assessment in children whose serology suggests celiac disease despite normal small bowel biopsy.
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Doença Celíaca , Autoanticorpos , Biópsia , Doença Celíaca/complicações , Doença Celíaca/diagnóstico , Criança , Humanos , Imunoglobulina A , Estudos RetrospectivosRESUMO
BACKGROUND: Hurricane Maria struck Puerto Rico on 20 September 2017 causing catastrophic devastation. Prolonged shortage of food had been a substantial challenge to the residents after Maria. Experiencing food insecurity in utero has been associated with negative health outcomes later in life. We aim to examine whether there is any alteration in the infant gut microbiome that is associated with prenatal food insecurity. METHODS: We established a cohort of infants aged 2-6 months who were exposed in utero to Hurricane Maria near San Juan, Puerto Rico and examined the gut microbiota (n = 29) using 16S ribosomal RNA gene sequencing. RESULTS: Among the enrolled infants, 30% of their mothers experienced "post-Maria poor access to food" for at least 1 month during pregnancy. The relative abundance of gut Veillonella spp. is significantly decreased among infants who experienced prenatal food insecurity, compared to those who did not (adjusted p = 0.025). There is no significant difference observed by prenatal food insecurity at the microbial community level in this cohort. CONCLUSIONS: Our finding indicated that infants who experienced prenatal food insecurity post hurricane harbor microbial alternations of specific bacterial taxa, which may further influence the microbial maturation and place the individual at a high-risk health trajectory. IMPACT: We identified that in utero exposure to food insecurity post Hurricane Maria is associated with decreased abundance of Veillonella in the infant gut. Our findings indicated that infants who experienced prenatal food insecurity post hurricane may harbor alterations of specific bacterial taxa in their gut microbiota. This study showed the association between prenatal adverse exposure and alterations of gut microbiome early in life in the context of an extreme event. This study provided insights into the mechanisms underlying prenatal adverse exposure and increased disease risks later in life. Our findings will potentially raise awareness of the negative impact of extreme climate events on the unborn.
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Tempestades Ciclônicas , Insegurança Alimentar , Microbioma Gastrointestinal , Microbiota , Efeitos Tardios da Exposição Pré-Natal , Veillonella/metabolismo , Clima , Feminino , Humanos , Lactente , Recém-Nascido , Mães , Reação em Cadeia da Polimerase , Gravidez , Porto Rico , RNA Ribossômico 16S/metabolismo , Resultado do TratamentoRESUMO
The incidence of gastroenteritis has greatly reduced due to improved hygiene conditions in developing countries and the use of rotavirus vaccine. Still thousands of children, however, die from gastroenteritis, most of them in poor countries. Yet gastroenteritis management is simple, inexpensive, and effective and is largely the same all over the world. Universal guidelines for gastroenteritis guide the management and include simple interventions put forward early in the course of the disease. Treatment includes rehydration, continuing oral feeding, and anti-infective drugs in selected clinical conditions related to the symptoms or to host-related risk, and possible additional drug treatment to reduce the duration and severity of symptoms. There may be minor geographical differences in the treatment applied due to health care organizations that do not substantially change the standard universal recommendations. Prevention is recommended with sanitation interventions and rotavirus universal immunization. Implementation of those interventions through educational initiatives and local programs in target areas are needed. A series of recommendations for interventions, education, and research priorities are included here with the aim of reducing the burden of gastroenteritis, to be pursued by scientists, physicians, policy makers, and stakeholders involved. They include the need of recommendations for the management of gastroenteritis in malnourished children, in those with chronic conditions, in neonates, and in emergency settings. A reference system to score dehydration, the definition of optimal composition of rehydration solution and the indications for anti-infective therapy are also included. Rotavirus immunization should be actively promoted, and evidence-based guidelines should be universally implemented. Research priorities are also indicated.
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Gastroenterite , Infecções por Rotavirus , Vacinas contra Rotavirus , Criança , Serviço Hospitalar de Emergência , Hidratação , Gastroenterite/epidemiologia , Gastroenterite/prevenção & controle , Humanos , Lactente , Recém-Nascido , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/prevenção & controle , VacinaçãoAssuntos
Bacteriófagos , Terapia por Fagos , Pneumonia , Humanos , Transplantados , Pulmão , ImunidadeRESUMO
Astrovirus VA1/HMO-C (VA1; mamastrovirus 9) is a recently discovered astrovirus genotype that is divergent from the classic human astroviruses (mamastrovirus 1). The gastrointestinal tract is presumed to be the primary site of infection and pathogenicity for astroviruses. However, VA1 has been independently detected in brain tissue of five cases of human encephalitis. Studies of the pathogenicity of VA1 are currently impossible because there are no reported cell culture systems or in vivo models that support VA1 infection. Here, we describe successful propagation of VA1 in multiple human cell lines. The initial inoculum, a filtered clinical stool sample from the index gastroenteritis case cluster that led to the discovery of VA1, was first passaged in Vero cells. Serial blind passage in Caco-2 cells yielded increasing copies of VA1 RNA, and multistep growth curves demonstrated a >100-fold increase in VA1 RNA 72 h after inoculation. The full-length genomic and subgenomic RNA strands were detected by Northern blotting, and crystalline lattices of viral particles of â¼26-nm diameter were observed by electron microscopy in infected Caco-2 cells. Unlike other human astrovirus cell culture systems, which require addition of exogenous trypsin for continued propagation, VA1 could be propagated equally well with or without the addition of trypsin. Furthermore, VA1 was sensitive to the type I interferon (IFN-I) response, as VA1 RNA levels were reduced by pretreatment of Caco-2 cells with IFN-ß1a. The ability to propagate VA1 in cell culture will facilitate studies of the neurotropism and neuropathogenesis of VA1.IMPORTANCE Astroviruses are an emerging cause of central nervous system infections in mammals, and astrovirus VA1/HMO-C is the most prevalent astrovirus in cases of human encephalitis. This virus has not been previously propagated, preventing elucidation of the biology of this virus. We describe the first cell culture system for VA1, a key step necessary for the study of its ability to cause disease.
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OBJECTIVES: This study examined risk and protective factors associated with very low birth weight (VLBW) for babies born to women receiving adequate or inadequate prenatal care. METHODS: Birth records from St. Louis City and County from 2000 to 2009 were used (n = 152,590). Data was categorized across risk factors and stratified by adequacy of prenatal care (PNC). Multivariate logistic regression and population attributable risk (PAR) was used to explore risk factors for VLBW infants. RESULTS: Women receiving inadequate prenatal care had a higher prevalence of delivering a VLBW infant than those receiving adequate PNC (4.11 vs. 1.44 %, p < .0001). The distribution of risk factors differed between adequate and inadequate PNC regarding Black race (36.4 vs. 79.0 %, p < .0001), age under 20 (13.0 vs. 33.6 %, p < .0001), <13 years of education (35.9 vs. 77.9 %, p < .0001), Medicaid status (35.7 vs. 74.9, p < .0001), primiparity (41.6 vs. 31.4 %, p < .0001), smoking (9.7 vs. 24.5 %, p < .0001), and diabetes (4.0 vs. 2.4 %, p < .0001), respectively. Black race, advanced maternal age, primiparity and gestational hypertension were significant predictors of VLBW, regardless of adequate or inadequate PNC. Among women with inadequate PNC, Medicaid was protective against (aOR 0.671, 95 % CI 0.563-0.803; PAR -32.6 %) and smoking a risk factor for (aOR 1.23, 95 % CI 1.01, 1.49; PAR 40.1 %) VLBW. When prematurity was added to the adjusted models, the largest PAR shifts to education (44.3 %) among women with inadequate PNC. CONCLUSIONS: Community actions around broader issues of racism and social determinants of health are needed to prevent VLBW in a large urban area.
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Recém-Nascido de muito Baixo Peso , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Cuidado Pré-Natal/estatística & dados numéricos , Fatores de Proteção , Adulto , Estudos de Coortes , Escolaridade , Feminino , Humanos , Hipertensão Induzida pela Gravidez/epidemiologia , Recém-Nascido , Recém-Nascido Prematuro , Modelos Logísticos , Idade Materna , Medicaid , Missouri/epidemiologia , Análise Multivariada , Paridade , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Gravidez , Prevalência , Fatores de Risco , Estados Unidos , População Urbana/estatística & dados numéricos , Adulto JovemRESUMO
BACKGROUND: Infectious diarrhea leads to significant mortality in children, with 40 % of these deaths occurring in Africa. Classic human astroviruses are a well-established etiology of diarrhea. In recent years, seven novel astroviruses have been discovered (MLB1, MLB2, MLB3, VA1/HMO-C, VA2/HMO-B, VA3/HMO-A, VA4); however, there have been few studies on their prevalence or potential association with diarrhea. METHODS: To investigate the prevalence and diversity of these classic and recently described astroviruses in a pediatric population, a case-control study was performed. Nine hundred and forty nine stools were previously collected from cases of moderate-to-severe diarrhea and matched controls of patients less than 5 years of age in Kenya and The Gambia. RT-PCR screening was performed using pan-astrovirus primers. RESULTS: Astroviruses were present in 9.9 % of all stool samples. MLB3 was the most common astrovirus with a prevalence of 2.6 %. Two subtypes of MLB3 were detected that varied based on location in Africa. In this case-control study, Astrovirus MLB1 was associated with diarrhea in Kenya, whereas Astrovirus MLB3 was associated with the control state in The Gambia. Classic human astrovirus was not associated with diarrhea in this study. Unexpectedly, astroviruses with high similarity to Canine Astrovirus and Avian Nephritis Virus 1 and 2 were also found in one case of diarrhea and two control stools respectively. CONCLUSIONS: Astroviruses including novel MLB- and VA-clade members are commonly found in pediatric stools in Kenya and The Gambia. The most recently discovered astrovirus, MLB3, was the most prevalent and was found more commonly in control stools in The Gambia, while astrovirus MLB1 was associated with diarrhea in Kenya. Furthermore, a distinct subtype of MLB3 was noted, as well as 3 unanticipated avian or canine astroviruses in the human stool samples. As a result of a broadly reactive PCR screen for astroviruses, new insight was gained regarding the epidemiology of astroviruses in Africa, where a large proportion of diarrheal morbidity and mortality occur.
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Infecções por Astroviridae/epidemiologia , Infecções por Astroviridae/virologia , Avastrovirus/classificação , Avastrovirus/isolamento & purificação , Diarreia/epidemiologia , Diarreia/virologia , Variação Genética , Astroviridae , Avastrovirus/genética , Estudos de Casos e Controles , Pré-Escolar , Análise por Conglomerados , Fezes/virologia , Feminino , Gâmbia/epidemiologia , Humanos , Lactente , Recém-Nascido , Quênia/epidemiologia , Masculino , Mamastrovirus , Dados de Sequência Molecular , Filogenia , Prevalência , RNA Viral/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA , Homologia de SequênciaRESUMO
INTRODUCTION: Circulating tissue transglutaminase immunoglobulin A concentration is a sensitive and specific indicator of celiac disease, but discrepancies between serologic and histologic findings occur. We hypothesized that fecal markers of inflammation and protein loss would be greater in patients with untreated celiac disease than in healthy controls. Our study aims to evaluate multiple fecal and plasma markers in celiac disease and correlate these findings with serologic and histologic findings as noninvasive means of evaluating disease activity. METHODS: Participants with positive celiac serologies and controls with negative celiac serologies were prospectively enrolled before upper endoscopy. Blood, stool, and duodenal biopsies were collected. Concentrations of fecal lipocalin-2, calprotectin, and alpha-1-antitrypsin and plasma lipocalin-2 were determined. Biopsies underwent modified Marsh scoring. Significance was tested between cases and controls, modified Marsh score and tissue transglutaminase immunoglobulin A concentration. RESULTS: Lipocalin-2 was significantly elevated in the stool ( P = 0.006) but not the plasma of participants with positive celiac serologies. There was no significant difference in fecal calprotectin or alpha-1 antitrypsin between participants with positive celiac serologies and controls. Fecal alpha-1 antitrypsin >100 mg/dL was specific, but not sensitive for biopsy-proven celiac disease. DISCUSSION: Lipocalin-2 is elevated in the stool but not the plasma of patients with celiac disease suggesting a role of local inflammatory response. Calprotectin was not a useful marker in the diagnosis of celiac disease. While random fecal alpha-1 antitrypsin was not significantly elevated in cases compared with controls, an elevation of greater than 100 mg/dL was 90% specific for biopsy-proven celiac disease.
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Biomarcadores , Doença Celíaca , Duodeno , Fezes , Proteínas de Ligação ao GTP , Imunoglobulina A , Complexo Antígeno L1 Leucocitário , Lipocalina-2 , Proteína 2 Glutamina gama-Glutamiltransferase , Transglutaminases , alfa 1-Antitripsina , Humanos , Doença Celíaca/diagnóstico , Doença Celíaca/sangue , Doença Celíaca/patologia , Feminino , Biomarcadores/sangue , Biomarcadores/análise , Masculino , Criança , alfa 1-Antitripsina/sangue , Complexo Antígeno L1 Leucocitário/análise , Complexo Antígeno L1 Leucocitário/sangue , Fezes/química , Lipocalina-2/sangue , Lipocalina-2/análise , Transglutaminases/imunologia , Transglutaminases/sangue , Estudos Prospectivos , Pré-Escolar , Imunoglobulina A/sangue , Proteínas de Ligação ao GTP/imunologia , Proteínas de Ligação ao GTP/sangue , Adolescente , Duodeno/patologia , Biópsia , Estudos de Casos e Controles , Lipocalinas/sangue , Proteínas de Fase Aguda/análise , Proteínas de Fase Aguda/metabolismo , Inflamação/diagnóstico , Inflamação/sangueRESUMO
Background and Aims: The dual sugar absorption test as a classic measure of human intestinal permeability has limited clinical utility due to lengthy and cumbersome urine collection, assay variability, and long turnaround. We aimed to determine if the orally administered fluorophore MB-102 (relmapirazin) (molecular weight [MW] = 372) compares to lactulose (L) (MW = 342) and rhamnose (R) (MW = 164)-based dual sugar absorption test as a measure of gut permeability in people with a spectrum of permeability including those with Crohn's disease (CD). Methods: We performed a single-center, randomized, open-label, crossover study comparing orally administered MB-102 (1.5 or 3.0 mg/kg) to L (1000 mg) and R (200 mg). Adults with active small bowel CD on magnetic resonance enterography (cases) and healthy adults (controls) were randomized to receive either MB-102 or L and R on study day 1, and the other tracer 3 to 7 days later. Urine was collected at baseline and 1, 2, 4, 6, 8, 10, and 12 hours after tracer ingestion to calculate the cumulative urinary percent excretion of MB-102 and L and R. Results: Nine cases and 10 controls completed the study without serious adverse events. Urinary recovery of administered MB-102 correlated with recovery of lactulose (r-squared = 0.83) for all participants. MB-102 urine recovery was also tracked with the L:R ratio urine recovery (r-squared = 0.57). In controls, the percentages of L and MB-102 recovered were similar within a narrow range, unlike in CD patients. Conclusion: This first-in-human study of an orally administered fluorophore to quantify gastrointestinal permeability in adults with CD demonstrates that MB-102 is well tolerated, and its recovery in urine mirrors that of percent L and the L:R ratio.
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Background: Circulating tissue transglutaminase IgA (TTG IgA) concentrations are sensitive and specific indicators of celiac disease, but discrepancies between serologic and histologic findings still occur. We hypothesized that fecal markers of inflammation and protein loss would be greater in patients with untreated celiac disease than in healthy controls. Our study aims to evaluate multiple fecal and plasma markers in celiac disease and correlate these findings with serologic and histologic findings as non-invasive means of evaluating disease activity. Methods: Participants with positive celiac serologies and controls with negative celiac serologies were enrolled at the time of upper endoscopy. Blood, stool and duodenal biopsies were collected. Concentrations of fecal lipocalin-2, calprotectin and alpha-1-antitrypsin and plasma lipcalin-2 were determined. Biopsies underwent modified Marsh scoring. Significance was tested between cases and controls, modified Marsh score and TTG IgA concentration. Results: Lipocalin-2 was significantly elevated in the stool ( p =0.007) but not the plasma of participants with positive celiac serologies compared to controls. There was no significant difference in fecal calprotectin or alpha-1 antitrypsin between participants with positive celiac serologies and controls. Fecal alpha-1 antitrypsin >100mg/dL was specific, but not sensitive for biopsy proven celiac disease. Conclusions: Lipocalin-2 is elevated in the stool but not the plasma of patients with celiac disease suggesting a role in the local inflammatory response. Calprotectin was not a useful marker in the diagnosis of celiac disease and did not correlate with degree of histologic changes on biopsy. While random fecal alpha-1 antitrypsin was not significantly elevated in cases compared to controls, an elevation of greater than 100mg/dL was 90% specific for biopsy proven celiac disease.
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Immunocompromised patients are at risk for disease caused by infection by some polyomaviruses. To define the prevalence of polyomaviruses in children undergoing transplantation, we collected samples from a longitudinal cohort and tested for the 9 known human polyomaviruses. All were detected; several were present in previously unreported specimen types.
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Transplante de Medula Óssea/efeitos adversos , Transplante de Órgãos/efeitos adversos , Infecções por Polyomavirus/epidemiologia , Polyomavirus/genética , Criança , Pré-Escolar , Feminino , Humanos , Hospedeiro Imunocomprometido , Masculino , Reação em Cadeia da Polimerase , Polyomavirus/classificação , Polyomavirus/isolamento & purificação , Infecções por Polyomavirus/virologia , Prevalência , Estados Unidos/epidemiologiaRESUMO
The human body is colonized by a multitude of bacteria, fungi, and viruses, which play important roles in health and disease. Microbial colonization during early life is thought to be a particularly important period with lasting consequences for health. Viral populations in the gut are particularly dynamic in early life before they stabilize in adulthood. The composition of the early-life virome is increasingly recognized as a determinant of disease later in life. Here, we review the development of the virome in healthy infants, as well as the role of the early-life virome in the development of disease states including diarrhea, malnutrition, and autoimmune diseases.
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Microbioma Gastrointestinal , Vírus , Adulto , Bactérias , Humanos , Lactente , Viroma , Vírus/genéticaRESUMO
OBJECTIVE: To investigate viral prevalence in a large neonatal cohort and determine the impact on pregnancy and birth outcomes. STUDY DESIGN: We prospectively collected 1044 neonatal samples from remnant neonatal cord blood RPR samples. We performed qRT-PCR/qPCR reactions for: adenovirus, anellovirus (alphatorquevirus and betatorquevirus), cytomegalovirus (CMV), Epstein-Barr virus (EBV), enterovirus, human herpesvirus 6 (HHV6), parechovirus, and parvovirus B19. RESULT: Overall viral prevalence was 5.6% with 58 positive samples. Alphatorquevirus (2%) and HHV6 (1.2%) were the two most prevalent viruses detected. Viral detection was most common in samples collected in the fall (September-November) and least common in those collected in winter (December-February). There was no statistical difference detected in viral prevalence or viral load by gestational age, preterm delivery, pre-eclampsia or chorioamnionitis. CONCLUSION: While there is seasonal variation in viral prevalence in neonatal cord blood samples, individual virus presence does not seem to effect pregnancy or birth outcomes.
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Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Gravidez , Recém-Nascido , Feminino , Humanos , Herpesvirus Humano 4/genética , Estações do Ano , Sangue Fetal/química , DNA Viral/análise , Prevalência , Idade GestacionalRESUMO
OBJECTIVE: To determine the prevalence of virus in a previously uncharacterized matched maternal-infant preterm cohort and test if viral presence or viral load correlate with histologic chorioamnionitis, spontaneous preterm labor or pre-eclampsia. STUDY DESIGN: Using qRT-PCR/qPCR we tested plasma or whole blood samples from 56 matched maternal and premature infant dyads for: adenovirus, anellovirus (alphatorquevirus and betatorquevirus), cytomegalovirus (CMV), Epstein-Barr virus (EBV), enterovirus, human herpesvirus 6 (HHV6), parechovirus, and parvovirus B19. RESULT: Viral detection was more common in maternal samples 29/56 (52%) than in cord blood from their infants (4/56 (7%)) (p ≤ .0001). No significant difference in viral load or viral prevalence was identified between pregnancies with and without histologic chorioamnionitis, spontaneous preterm labor or pre-eclampsia. CONCLUSION: Despite frequent detection of virus in maternal samples, virus was less frequently detected in the infants. Additionally, there was no association of presence or quantity of virus in maternal blood with histologic chorioamnionitis, spontaneous preterm labor or pre-eclampsia in this small, but well-defined cohort. Future studies are necessary to further characterize the role of virus in placental inflammatory states and pregnancy outcomes.
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Anelloviridae , Corioamnionite , Infecções por Vírus Epstein-Barr , Trabalho de Parto Prematuro , Corioamnionite/diagnóstico , Feminino , Herpesvirus Humano 4 , Humanos , Recém-Nascido , Trabalho de Parto Prematuro/epidemiologia , Placenta/patologia , GravidezRESUMO
Necrotizing enterocolitis (NEC) is a serious consequence of preterm birth and is often associated with gut bacterial microbiome alterations. However, little is known about the development of the gut virome in preterm infants, or its role in NEC. Here, using metagenomic sequencing, we characterized the DNA gut virome of 9 preterm infants who developed NEC and 14 gestational age-matched preterm infants who did not. Infants were sampled longitudinally before NEC onset over the first 11 weeks of life. We observed substantial interindividual variation in the gut virome between unrelated preterm infants, while intraindividual variation over time was significantly less. We identified viral and bacterial signatures in the gut that preceded NEC onset. Specifically, we observed a convergence towards reduced viral beta diversity over the 10 d before NEC onset, which was driven by specific viral signatures and accompanied by specific viral-bacterial interactions. Our results indicate that bacterial and viral perturbations precede the sudden onset of NEC. These findings suggest that early life virome signatures in preterm infants may be implicated in NEC.