Microbial Co-occurrence Relationships in the Human Microbiome

The healthy microbiota show remarkable variability within and among individuals. In addition to external exposures, ecological relationships (both oppositional and symbiotic) between microbial inhabitants are important contributors to this variation. It is thus of interest to assess what relationships might exist among microbes and determine their underlying reasons. The initial Human Microbiome Project (HMP) cohort, comprising 239 individuals and 18 different microbial habitats, provides an unprecedented resource to detect, catalog, and analyze such relationships. Here, we applied an ensemble method based on multiple similarity measures in combination with generalized boosted linear models (GBLMs) to taxonomic marker (16S rRNA gene) profiles of this cohort, resulting in a global network of 3,005 significant co-occurrence and co-exclusion relationships between 197 clades occurring throughout the human microbiome. This network revealed strong niche specialization, with most microbial associations occurring within body sites and a number of accompanying inter-body site relationships. Microbial communities within the oropharynx grouped into three distinct habitats, which themselves showed no direct influence on the composition of the gut microbiota. Conversely, niches such as the vagina demonstrated little to no decomposition into region-specific interactions. Diverse mechanisms underlay individual interactions, with some such as the co-exclusion of Porphyromonaceae family members and Streptococcus in the subgingival plaque supported by known biochemical dependencies. These differences varied among broad phylogenetic groups as well, with the Bacilli and Fusobacteria, for example, both enriched for exclusion of taxa from other clades. Comparing phylogenetic versus functional similarities among bacteria, we show that dominant commensal taxa (such as Prevotellaceae and Bacteroides in the gut) often compete, while potential pathogens (e.g. Treponema and Prevotella in the dental plaque) are more likely to co-occur in complementary niches. This approach thus serves to open new opportunities for future targeted mechanistic studies of the microbial ecology of the human microbiome.National Institutes of Health (U.S.) (grant CA139193)Fonds Wetenschappelijk Onderzoek – VlaanderenJuvenile Diabetes Research Foundation InternationalNational Institutes of Health (U.S.) (grant NIH U54HG004969)Crohn's and Colitis Foundation of AmericaNational Science Foundation (U.S.) (NSF DBI-1053486)United States. Army Research Office (ARO W911NF-11-1-0473)National Institutes of Health (U.S.) (grant NIH 1R01HG005969

Supplementary Material for: Pilot Study Using Proteomics to Identify Predictive Biomarkers of Necrotizing Enterocolitis from Buccal Swabs in Very Low Birth Weight Infants

<b><i>Background:</i></b> Necrotizing enterocolitis (NEC) is a major cause of death and morbidity in very low birth weight infants. <b><i>Objective:</i></b> To identify biomarker(s) that would predict NEC using buccal swab samples utilizing a proteomic approach. <b><i>Methods:</i></b> Cumulative buccal swab samples derived from very low birth weight preterm infants (<32 weeks' gestational age and <1,250 g) at 1, 2 and 3 weeks prior to the development of NEC and matched controls were subjected to two-dimensional difference gel electrophoresis and LC-MS/MS analysis for proteomic protein discovery. After identification of 21 altered proteins, we chose 3 candidate proteins using a broad systems biologic analysis approach that suggested several altered cellular processes that could be associated with NEC. <b><i>Results:</i></b> Preliminary validation studies using Western blots on these samples and 10 additional NEC and 10 matched control buccal samples collected within 2 or 3 weeks before NEC diagnosis analysis showed lower interleukin-1 receptor antagonist. <b><i>Conclusion:</i></b> Our results suggest that interleukin-1 receptor antagonist is worthy of further studies to determine its utility in helping predict NEC

Meconium Microbiome Analysis Identifies Bacteria Correlated with Premature Birth

BACKGROUND: Preterm birth is the second leading cause of death in children under the age of five years worldwide, but the etiology of many cases remains enigmatic. The dogma that the fetus resides in a sterile environment is being challenged by recent findings and the question has arisen whether microbes that colonize the fetus may be related to preterm birth. It has been posited that meconium reflects the in-utero microbial environment. In this study, correlations between fetal intestinal bacteria from meconium and gestational age were examined in order to suggest underlying mechanisms that may contribute to preterm birth. METHODS: Meconium from 52 infants ranging in gestational age from 23 to 41 weeks was collected, the DNA extracted, and 16S rRNA analysis performed. Resulting taxa of microbes were correlated to clinical variables and also compared to previous studies of amniotic fluid and other human microbiome niches. FINDINGS: Increased detection of bacterial 16S rRNA in meconium of infants of <33 weeks gestational age was observed. Approximately 61·1% of reads sequenced were classified to genera that have been reported in amniotic fluid. Gestational age had the largest influence on microbial community structure (R = 0·161; p = 0·029), while mode of delivery (C-section versus vaginal delivery) had an effect as well (R = 0·100; p = 0·044). Enterobacter, Enterococcus, Lactobacillus, Photorhabdus, and Tannerella, were negatively correlated with gestational age and have been reported to incite inflammatory responses, suggesting a causative role in premature birth. INTERPRETATION: This provides the first evidence to support the hypothesis that the fetal intestinal microbiome derived from swallowed amniotic fluid may be involved in the inflammatory response that leads to premature birth