Loss of murine Paneth cell function alters the immature intestinal microbiome and mimics changes seen in neonatal necrotizing enterocolitis

Necrotizing enterocolitis (NEC) remains the leading cause of gastrointestinal morbidity and mortality in premature infants. Human and animal studies suggest a role for Paneth cells in NEC pathogenesis. Paneth cells play critical roles in host-microbial interactions and epithelial homeostasis. The ramifications of eliminating Paneth cell function on the immature host-microbial axis remains incomplete. Paneth cell function was depleted in the immature murine intestine using chemical and genetic models, which resulted in intestinal injury consistent with NEC. Paneth cell depletion was confirmed using histology, electron microscopy, flow cytometry, and real time RT-PCR. Cecal samples were analyzed at various time points to determine the effects of Paneth cell depletion with and without Klebsiella gavage on the microbiome. Deficient Paneth cell function induced significant compositional changes in the cecal microbiome with a significant increase in Enterobacteriacae species. Further, the bloom of Enterobacteriaceae species that occurs is phenotypically similar to what is seen in human NEC. This further strengthens our understanding of the importance of Paneth cells to intestinal homeostasis in the immature intestine

Young volcanism and related hydrothermal activity at 5°S on the slow-spreading southern Mid-Atlantic Ridge

The effect of volcanic activity on submarine hydrothermal systems has been well documented along fast- and intermediate-spreading centers but not from slow-spreading ridges. Indeed, volcanic eruptions are expected to be rare on slow-spreading axes. Here we report the presence of hydrothermal venting associated with extremely fresh lava flows at an elevated, apparently magmatically robust segment center on the slow-spreading southern Mid-Atlantic Ridge near 5°S. Three high-temperature vent fields have been recognized so far over a strike length of less than 2 km with two fields venting phase-separated, vapor-type fluids. Exit temperatures at one of the fields reach up to 407°C, at conditions of the critical point of seawater, the highest temperatures ever recorded from the seafloor. Fluid and vent field characteristics show a large variability between the vent fields, a variation that is not expected within such a limited area. We conclude from mineralogical investigations of hydrothermal precipitates that vent-fluid compositions have evolved recently from relatively oxidizing to more reducing conditions, a shift that could also be related to renewed magmatic activity in the area. Current high exit temperatures, reducing conditions, low silica contents, and high hydrogen contents in the fluids of two vent sites are consistent with a shallow magmatic source, probably related to a young volcanic eruption event nearby, in which basaltic magma is actively crystallizing. This is the first reported evidence for direct magmatic-hydrothermal interaction on a slow-spreading mid-ocean ridge

What determines cell size?

AbstractFirst paragraph (this article has no abstract) For well over 100 years, cell biologists have been wondering what determines the size of cells. In modern times, we know all of the molecules that control the cell cycle and cell division, but we still do not understand how cell size is determined. To check whether modern cell biology has made any inroads on this age-old question, BMC Biology asked several heavyweights in the field to tell us how they think cell size is controlled, drawing on a range of different cell types. The essays in this collection address two related questions - why does cell size matter, and how do cells control it

Bacterial colonization and antimicrobial resistance genes in neonatal enteral feeding tubes.

Enteral feeding is a key component of care in neonatal intensive care units (NICUs); however, feeding tubes harbor microbes. These microbes have the potential to cause disease, yet their source remains controversial and clinical recommendations to reduce feeding tube colonization are lacking. This study aims to improve our understanding of the bacteria in neonatal feeding tubes and to evaluate factors that may affect these bacteria. 16S rRNA gene sequencing was used to characterize the bacteria present in pharyngeal, esophageal, and gastric portions of feeding tubes, residual fluid of the tubes, and infant stool using samples from 47 infants. Similar distributions of taxa were observed in all samples, although beta diversity differed by sample type. Feeding tube samples had lower alpha diversity than stool samples, and alpha diversity increased with gestational age, day of life, and tube dwell time. In a subset of samples from 6 infants analyzed by whole metagenome sequencing, there was greater overlap in transferable antimicrobial resistance genes between tube and fecal samples in breast milk fed infants than in formula fed infants. These findings develop our understanding of neonatal feeding tube colonization, laying a foundation for research into methods for minimizing NICU patients' exposure to antimicrobial resistant microbes

A comparison of bacterial colonization between nasogastric and orogastric enteral feeding tubes in infants in the neonatal intensive care unit

ObjectiveFeeding tubes harbor microbial contaminants; studies to date have not explored differences between orogastric (OG) and nasogastric (NG) tube biofilms. We sought to extend a previous analysis by comparing bacterial colonization by location (OG v NG) and by evaluating clinical factors that may affect tube bacterial populations.Study designThe pharyngeal segments of 41 infant feeding tubes (14 OG and 27 NG) from 41 infants were analyzed by next generation 16 S rRNA sequencing on the MiSeq platform.ResultsAt the phylum level, Proteobacteria had the highest relative abundance of both OG and NG tubes. At the genus/species level, nine taxa differed significantly between OG and NG tubes. Alpha and beta diversity analyses showed significant differences between OG and NG tubes with relatively little contribution from clinical factors.ConclusionThe route of feeding tube insertion (oral vs nasal) had a greater impact on bacterial colonization than the assessed clinical factors

Stool Microbiota and Vaccine Responses of Infants

OBJECTIVE: Oral vaccine efficacy is low in less-developed countries, perhaps due to intestinal dysbiosis. This study determined if stool microbiota composition predicted infant oral and parenteral vaccine responses. METHODS: The stool microbiota of 48 Bangladeshi infants was characterized at 6, 11, and 15 weeks of age by amplification and sequencing of the 16S ribosomal RNA gene V4 region and by Bifidobacterium-specific, quantitative polymerase chain reaction. Responses to oral polio virus (OPV), bacille Calmette-Guérin (BCG), tetanus toxoid (TT), and hepatitis B virus vaccines were measured at 15 weeks by using vaccine-specific T-cell proliferation for all vaccines, the delayed-type hypersensitivity skin-test response for BCG, and immunoglobulin G responses using the antibody in lymphocyte supernatant method for OPV, TT, and hepatitis B virus. Thymic index (TI) was measured by ultrasound. RESULTS: Actinobacteria (predominantly Bifidobacterium longum subspecies infantis) dominated the stool microbiota, with Proteobacteria and Bacteroidetes increasing by 15 weeks. Actinobacteria abundance was positively associated with T-cell responses to BCG, OPV, and TT; with the delayed-type hypersensitivity response; with immunoglobulin G responses; and with TI. B longum subspecies infantis correlated positively with TI and several vaccine responses. Bacterial diversity and abundance of Enterobacteriales, Pseudomonadales, and Clostridiales were associated with neutrophilia and lower vaccine responses. CONCLUSIONS: Bifidobacterium predominance may enhance thymic development and responses to both oral and parenteral vaccines early in infancy, whereas deviation from this pattern, resulting in greater bacterial diversity, may cause systemic inflammation (neutrophilia) and lower vaccine responses. Vaccine responsiveness may be improved by promoting intestinal bifidobacteria and minimizing dysbiosis early in infancy

Western Diet-Induced Dysbiosis in Farnesoid X Receptor Knockout Mice Causes Persistent Hepatic Inflammation after Antibiotic Treatment.

Patients who have liver cirrhosis and liver cancer also have reduced farnesoid X receptor (FXR). The current study analyzes the effect of diet through microbiota that affect hepatic inflammation in FXR knockout (KO) mice. Wild-type and FXR KO mice were on a control (CD) or Western diet (WD) for 10 months. In addition, both CD- and WD-fed FXR KO male mice, which had hepatic lymphocyte and neutrophil infiltration, were treated by vancomycin, polymyxin B, and Abx (ampicillin, neomycin, metronidazole, and vancomycin). Mice were subjected to morphological analysis as well as gut microbiota and bile acid profiling. Male WD-fed FXR KO mice had the most severe steatohepatitis. FXR KO also had reduced Firmicutes and increased Proteobacteria, which could be reversed by Abx. In addition, Abx eliminated hepatic neutrophils and lymphocytes in CD-fed, but not WD-fed, FXR KO mice. Proteobacteria and Bacteroidetes persisted in WD-fed FXR KO mice even after Abx treatment. Only polymyxin B could reduce hepatic lymphocytes in WD-fed FXR KO mice. The reduced hepatic inflammation by antibiotics was accompanied by decreased free and conjugated secondary bile acids as well as changes in gut microbiota. Our data revealed that Lactococcus, Lactobacillus, and Coprococcus protect the liver from inflammation