Fecal tryptophan metabolite profiling in newborns in relation to microbiota and antibiotic treatment.

In the first days of life, the newborns' intestinal microbiota develops simultaneously with the intestinal gut barrier and follows intestinal immunity. The mode of delivery shows significant impact on microbial development and, thus, the initiation of the tryptophan catabolism pathway. Further antibiotics (ATB) treatment of mothers before or during delivery affects the microbial and tryptophan metabolite composition of stool of the caesarean- and vaginal-delivered newborns. The determination of microbiome and levels of tryptophan microbial metabolites in meconium and stool can characterize intestinal colonization of a newborn. From 134 samples from the Central European Longitudinal Studies of Parents and Children: The Next Generation (CELSPAC: TNG) cohort study, 16S rRNA gene sequencing was performed, and microbial tryptophan metabolites were quantified using ultra-high-performance liquid chromatography with triple-quadrupole mass spectrometry. Microbial diversity and concentrations of tryptophan metabolites were significantly higher in stool compared to meconium. Treatment of mothers with ATB before or during delivery affects metabolite composition and microbial diversity in stool of vaginal- and caesarean-delivered newborns. Correlation of microbial and metabolite composition shows significant positive correlations of indol-3-lactic acid, N-acetyl-tryptophan and indol-3-acetic acid with Bifidobacterium, Bacteroides and Peptoclostridium. The positive effect of vaginal delivery on newborns' microbiome development is degraded when mother is treated with ATB before or during delivery. KEY POINTS: • Antibiotic treatment diminishes the positive effects of vaginal delivery. • Antibiotic treatment affects metabolite and microbial composition in newborns. • Bifidobacterium and Peptoclostridium could be the producer of indole-lactic acid.

Enrichment of human nasopharyngeal bacteriome with bacteria from dust after short-term exposure to indoor environment: a pilot study.

BACKGROUND: Indoor dust particles are an everyday source of human exposure to microorganisms and their inhalation may directly affect the microbiota of the respiratory tract. We aimed to characterize the changes in human nasopharyngeal bacteriome after short-term exposure to indoor (workplace) environments. METHODS: In this pilot study, nasopharyngeal swabs were taken from 22 participants in the morning and after 8 h of their presence at the workplace. At the same time points, indoor dust samples were collected from the participants' households (16 from flats and 6 from houses) and workplaces (8 from a maternity hospital - NEO, 6 from a pediatric hospital - ENT, and 8 from a research center - RCX). 16S rRNA sequencing analysis was performed on these human and environmental matrices. RESULTS: Staphylococcus and Corynebacterium were the most abundant genera in both indoor dust and nasopharyngeal samples. The analysis indicated lower bacterial diversity in indoor dust samples from flats compared to houses, NEO, ENT, and RCX (p < 0.05). Participants working in the NEO had the highest nasopharyngeal bacterial diversity of all groups (p < 0.05). After 8 h of exposure to the workplace environment, enrichment of the nasopharynx with several new bacterial genera present in the indoor dust was observed in 76% of study participants; however, no significant changes were observed at the level of the nasopharyngeal bacterial diversity (p > 0.05, Shannon index). These "enriching" bacterial genera overlapped between the hospital workplaces - NEO and ENT but differed from those in the research center - RCX. CONCLUSIONS: The results suggest that although the composition of nasopharyngeal bacteriome is relatively stable during the day. Short-term exposure to the indoor environment can result in the enrichment of the nasopharynx with bacterial DNA from indoor dust; the bacterial composition, however, varies by the indoor workplace environment.

Evaluation of Microbiome-Host Relationships in the Zebrafish Gastrointestinal System Reveals Adaptive Immunity Is a Target of Bis(2-ethylhexyl) Phthalate (DEHP) Exposure.

To improve physical characteristics of plastics such as flexibility and durability, producers enrich materials with phthalates such as di-2-(ethylhexyl) phthalate (DEHP). DEHP is a high production volume chemical associated with metabolic and immune disruption in animals and humans. To reveal mechanisms implicated in phthalate-related disruption in the gastrointestinal system, male and female zebrafish were fed DEHP (3 ppm) daily for two months. At the transcriptome level, DEHP significantly upregulated gene networks in the intestine associated with helper T cells' (Th1, Th2, and Th17) specific pathways. The activation of gene networks associated with adaptive immunity was linked to the suppression of networks for tight junction, gap junctional intercellular communication, and transmembrane transporters, all of which are precursors for impaired gut integrity and performance. On a class level, DEHP exposure increased Bacteroidia and Gammaproteobacteria and decreased Verrucomicrobiae in both the male and female gastrointestinal system. Further, in males there was a relative increase in Fusobacteriia and Betaproteobacteria and a relative decrease in Saccharibacteria. Predictive algorithms revealed that the functional shift in the microbiome community, and the metabolites they produce, act to modulate intestinal adaptive immunity. This finding suggests that the gut microbiota may contribute to the adverse effects of DEHP on the host by altering metabolites sensed by both intestinal and immune Th cells. Our results suggest that the microbiome-gut-immune axis can be modified by DEHP and emphasize the value of multiomics approaches to study microbiome-host interactions following chemical perturbations.

Colorectal Tumour Mucosa Microbiome Is Enriched in Oral Pathogens and Defines Three Subtypes That Correlate with Markers of Tumour Progression.

Long-term dysbiosis of the gut microbiome has a significant impact on colorectal cancer (CRC) progression and explains part of the observed heterogeneity of the disease. Even though the shifts in gut microbiome in the normal-adenoma-carcinoma sequence were described, the landscape of the microbiome within CRC and its associations with clinical variables remain under-explored. We performed 16S rRNA gene sequencing of paired tumour tissue, adjacent visually normal mucosa and stool swabs of 178 patients with stage 0-IV CRC to describe the tumour microbiome and its association with clinical variables. We identified new genera associated either with CRC tumour mucosa or CRC in general. The tumour mucosa was dominated by genera belonging to oral pathogens. Based on the tumour microbiome, we stratified CRC patients into three subtypes, significantly associated with prognostic factors such as tumour grade, sidedness and TNM staging, BRAF mutation and MSI status. We found that the CRC microbiome is strongly correlated with the grade, location and stage, but these associations are dependent on the microbial environment. Our study opens new research avenues in the microbiome CRC biomarker detection of disease progression while identifying its limitations, suggesting the need for combining several sampling sites (e.g., stool and tumour swabs).

Microbiome analysis and predicted relative metabolomic turnover suggest bacterial heme and selenium metabolism are altered in the gastrointestinal system of zebrafish (Danio rerio) exposed to the organochlorine dieldrin.

Dietary exposure to chemicals alters the diversity of microbiome communities and can lead to pathophysiological changes in the gastrointestinal system. The organochlorine pesticide dieldrin is a persistent environmental contaminant that bioaccumulates in fatty tissue of aquatic organisms. The objectives of this study were to determine whether environmentally-relevant doses of dieldrin altered gastrointestinal morphology and the microbiome of zebrafish. Adult zebrafish at ∼4 months of age were fed a measured amount of feed containing either a solvent control or one of two doses of dieldrin (measured at 16, and 163.5 ng/g dry weight) for 4 months. Dieldrin body burden levels in zebrafish after four-month exposure were 0 (control), 11.47 ± 1.13 ng/g (low dose) and 18.32 ± 1.32 ng/g (high dose) wet weight [mean ± std]. Extensive histopathology at the whole organism level revealed that dieldrin exposure did not induce notable tissue pathology, including the gastrointestinal tract. A repeated measure mixed model analysis revealed that, while fish gained weight over time, there were no dieldrin-specific effects on body weight. Fecal content was collected from the gastrointestinal tract of males and 16S rRNA gene sequencing conducted. Dieldrin at a measured feed dose of 16 ng/g reduced the abundance of Firmicutes, a phylum involved in energy resorption. At the level of class, there was a decrease in abundance of Clostridia and Betaproteobacteria, and an increase in Verrucomicrobiae species. We used a computational approach called predicted relative metabolomic turnover (PRMT) to predict how a shift in microbial community composition affects exchange of metabolites. Dieldrin was predicted to affect metabolic turnover of uroporphyrinogen I and coproporphyrinogen I [enzyme]-cysteine, hydrogen selenide, selenite, and methyl-selenic acid in the fish gastrointestinal system. These pathways are related to bacterial heme biosynthesis and selenium metabolism. Our study demonstrates that dietary exposures to dieldrin can alter microbiota composition over 4 months, however the long-term consequences of such impacts are not well understood.

Administration of the Probiotic Escherichia coli Strain A0 34/86 Resulted in a Stable Colonization of the Human Intestine During the First Year of Life.

Colinfant New Born (CNB) is an orally administered probiotic preparation containing the Escherichia coli strain A0 34/86, which is specially marketed for use in newborns and infants. Although the impact of different probiotics on the composition of the human gut microbiota has been previously described, the effects of E. coli probiotic consumption during infancy on the development of intestinal microbiota are not known. The effect of oral administration of CNB on the Enterobacteriaceae population was mapped using 16S rRNA gene sequencing in DNA samples isolated from the stools of one infant collected at 177 different time points during the first year of life. E. coli strains turnover was analyzed based on the detection of 26 genetic determinants, phylogroups, and pulsed-field gel electrophoresis (PFGE) analysis. Administration of CNB during the second and third month of life introduced the Escherichia genus to the infant's intestinal tract, and Escherichia became dominant among the Enterobacteriaceae family (p < 0.01). Genetic determinants, typical for probiotic E. coli A0 34/86 strain, were detected on the first day after application of CNB and persisted all year. In addition, nine transient E. coli strains were identified; these strains harbored different genetic determinants and showed different PFGE profiles. Transient strains were detected from 2 to 24 days in the stool samples. The first Escherichia colonizer originated from the application of the CNB probiotic preparation. Probiotic E. coli A0 34/86 successfully colonized the intestinal tract of an infant and became resident during the first year of life.