Viral dysbiosis in children with new-onset celiac disease

Viruses are common components of the intestinal microbiome, modulating host bacterial metabolism and interacting with the immune system, with a possible role in the pathogenesis of immune-mediated diseases such as celiac disease (CeD). The objective of this study was to characterize the virome profile in children with new-onset CeD. We used metagenomic analysis of viral DNA in mucosal and fecal samples from children with CeD and controls and performed sequencing using the Nextera XT library preparation kit. Abundance log2 fold changes were calculated using differential expression and linear discriminant effect size. Shannon alpha and Bray–Curtis beta diversity were determined. A total of 40 children with CeD and 39 controls were included. We found viral dysbiosis in both fecal and mucosal samples. Examples of significantly more abundant species in fecal samples of children with CeD included Human polyomavirus 2, Enterobacteria phage mEpX1, and Enterobacteria phage mEpX2; whereas less abundant species included Lactococcus phages ul36 and Streptococcus phage Abc2. In mucosal samples however, no species were significantly associated with CeD. Shannon alpha diversity was not significantly different between CeD and non-CeD groups and Bray–Curtis beta diversity showed no significant separation between CeD and non-CeD samples in either mucosal or stool samples, whereas separation was clear in all samples. We identified significant viral dysbiosis in children with CeD, suggesting a potential role in the pathogenesis of CeD indicating the need for further studies.

Longitudinal variability in the urinary microbiota of healthy premenopausal women and the relation to neighboring microbial communities: A pilot study

Background The understanding of longitudinal changes in the urinary microbiota of healthy women and its relation to intestinal microbiota is limited. Methods From a cohort of 15 premenopausal women without known urogenital disease or current symptoms, we collected catheter urine (CU), vaginal and periurethral swabs, and fecal samples on four visits over six months. Additionally, ten participants provided CU and midstream urine (MU) to assess comparability. Urine was subjected to expanded culture. 16S rRNA gene sequencing was performed on all urine, fecal, and selected vaginal and periurethral samples. Sequence reads were processed (DADA2 pipeline) and analyzed using QIIME 2 and R. Results Relative abundances of urinary microbiota were variable over 6–18 months. The degree of intraindividual variability of urinary microbiota was higher than that found in fecal samples. Still, nearly half of the observed beta diversity of all urine samples could be attributed to differences between volunteers (R2 = 0.48, p = 0.001). After stratification by volunteer, time since last sexual intercourse was shown to be a factor significantly contributing to beta diversity (R2 = 0.14, p = 0.001). We observed a close relatedness of urogenital microbial habitats and a clear distinction from intestinal microbiota in the overall betadiversity analysis. Microbiota compositions derived from MU differed only slightly from CU compositions. Within this analysis of low-biomass samples, we identified contaminating sequences potentially stemming from sequencing reagents. Conclusions Results from our longitudinal cohort study confirmed the presence of a rather variable individual urinary microbiota in premenopausal women. These findings from catheter urine complement previous observations on temporal dynamics in voided urine. The higher intraindividual variability of urinary microbiota as compared to fecal microbiota will be a challenge for future studies investigating associations with urogenital diseases and aiming at identifying pathogenic microbiota signatures.

Analysis of Psychological and Gut Microbiome Characteristics in Patients With Non-erosive Reflux Disease

Objective: To assess the correlation between the incidence of non-erosive reflux disease (NERD) and psychological factors, especially somatoform disorders. To investigate the characteristics of gut microbiome in NERD patients.Methods: We enrolled 24 NERD patients and 24 healthy controls. All patients were evaluated via GerdQ, SOMS-7, SAS, HAMA, and HAMD. Fecal samples were collected and 16S rRNA sequencing was performed to evaluate the gut microbiome composition.Results: The main symptoms of the NERD patients were regurgitation (87.5%), belching (66.7%), pharyngeal discomfort (50%), and heartburn (37.5%). The average score of GerdQ was 13.42 ± 3.41. In 15 patients (62.5%), the total score of the last two items was <3 points, while the average score of 24 patients was 3.63 ± 2.32. NERD patients with somatoform disorders accounted for 50%. There were 17 patients without anxiety, 6 patients with mild anxiety (25%), 1 patient with moderate anxiety (4.2%), and no patient with severe anxiety. There were 22 patients (91.7%) without depression, 2 patients (8.3%) with mild depression, and no patient with moderate or severe depression. The alpha diversity of NERD group was higher than HC, which showed significant difference (P < 0.05). The beta-diversity was significantly different between HC and NERD patients (P = 0.026), male and female patients (P = 0.009). The beta-diversity was also significantly different between male and female patients (P = 0.009). There were several bacteria with significant differences between HC and NERD group, and NERD patients with or without somatoform disorders, such as Firmicutes, TM7 were enriched in the NERD group compared with the healthy control group, while Bacteroidetes were enriched in the healthy controls.Conclusions: NERD symptoms overlap with somatoform disorders. NERD symptoms have an impact on the daily life quality of patients. Some of them are accompanied by anxiety and depression of different degrees, and the two are significantly correlated. The diversity of gut microbiome in patients with NERD is significantly higher than healthy controls, which has its characteristics. The predominant bacteria in gut microbiome of patients with NERD are similar to the healthy population, with Firmicutes and Bacteroidetes as the main ones. The composition of gut microbiome in NERD patients with or without somatoform disorder is significantly different, which may be related to the interaction of microbiome-brain-gut axis.

Age and injury size influence the magnitude of fecal dysbiosis in adult burn patients

Clinical studies have demonstrated that age ≥ 50 years old is an independent risk factor associated with poor prognosis after burn injury, the second leading cause of traumatic injuries in the aged population. While mechanisms driving age-dependent post-burn mortality are perplexing, changes in the intestinal microbiome however may contribute to the heightened, dysregulated systemic response seen in aging burn patients. The fecal microbiome from 22 patients admitted to a verified burn center from July 2018 to February 2019 were stratified based on age of 50 years and total burn surface area (TBSA) size of ≥10%. Significant differences (P = 0.014) in overall microbiota community composition (i.e., beta diversity) were measured across the four patient groups, young <10% TBSA, young ≥10% TBSA, older <10% TBSA, and older ≥10% TBSA. Differences in beta diversity were driven by %TBSA (P = 0.013) and trended with age (P = 0.087). Alpha diversity components, richness, evenness, and Shannon diversity were measured. We observed significant differences in bacterial species evenness (P = 0.0023) and Shannon diversity (P = 0.0033) between the groups. There were significant correlations between individual bacterial species and levels of SCFA. Specifically, levels of fecal butyrate correlated with the presence of Enterobacteriaceae, an opportunistic gut pathogen, when elevated in burn patients lead to worsen outcomes. Overall, our findings reveal that age-specific changes in the fecal microbiome following burn injuries may contribute to immune system dysregulation in patients with varying TBSA burns and potentially lead to worsen clinical outcomes with heightened morbidity and mortality.

Gut Microbiota in Heart Failure Patients With Preserved Ejection Fraction (GUMPTION Study)

Introduction: Heart failure with preserved ejection fraction (HFpEF) is associated with disrupted intestinal epithelial function, resulting from intestinal congestion. Intestinal congestion changes the morphology and permeability of the intestinal wall, and it becomes easy for the gut microbiota to change and transfer. Intervention on gut microbiota may become a new target for HFpEF treatment. However, the characteristics of gut microbiota in patients with HFpEF remain unknown. This preliminary report aims to detect the structure of gut microbiota in HFpEF patients so as to explore their characteristic changes, thereby providing a theoretical basis for future research.Methods: This research recruited 30 patients diagnosed with HFpEF and 30 healthy individuals. Stool specimens of research subjects were collected separately, and the microarray analyses of gut microbiota were conducted by Illumina high-throughput DNA sequencing. The differences in gut microbiota composition, alpha diversity, and beta diversity between the two groups were finally obtained.Results: The composition of gut microbiota was significantly different between the two groups. At the phylum classification level, the abundance of Synergistetes tended to be higher in the HFpEF group (P = 0.012). At genus classification level, the abundance of Butyricicoccus (P < 0.001), Sutterella (P = 0.004), Lachnospira (P = 0.003), and Ruminiclostridium (P = 0.009) in the HFpEF group were lower, while the abundance of Enterococcus (P < 0.001) and Lactobacillus (P = 0.005) were higher. According to the Chao index of alpha diversity analysis, HFpEF patients showed a nominally significant lower species richness when compared with controls (P = 0.046). However, there was no statistical difference in the Shannon index (P = 0.159) and Simpson index (P = 0.495), indicating that there was no difference in species diversity between the two groups. Beta diversity analysis revealed a highly significant separation of HFpEF patients and controls.Conclusions: An imbalance in the gut microbiota of HFpEF patients was observed. Patients with HFpEF have an increased abundance of microbiota associated with inflammation and a decreased abundance of microbiota associated with anti-inflammatory effects in the gut environment. In line with that, the species richness of gut microbiota in HFpEF patients tended to be lower.

The lower airways microbiome and antimicrobial peptides in idiopathic pulmonary fibrosis differ from chronic obstructive pulmonary disease

Background The lower airways microbiome and host immune response in chronic pulmonary diseases are incompletely understood. We aimed to investigate possible microbiome characteristics and key antimicrobial peptides and proteins in idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). Methods 12 IPF patients, 12 COPD patients and 12 healthy controls were sampled with oral wash (OW), protected bronchoalveolar lavage (PBAL) and right lung protected sterile brushings (rPSB). The antimicrobial peptides and proteins (AMPs), secretory leucocyte protease inhibitor (SLPI) and human beta defensins 1 and 2 (hBD-1 & hBD-2), were measured in PBAL by enzyme linked immunosorbent assay (ELISA). The V3V4 region of the bacterial 16S rDNA gene was sequenced. Bioinformatic analyses were performed with QIIME 2. Results hBD-1 levels in PBAL for IPF were lower compared with COPD. The predominant phyla in IPF were Firmicutes, Bacteroides and Actinobacteria; Proteobacteria were among top three in COPD. Differential abundance analysis at genus level showed significant differences between study groups for less abundant, mostly oropharyngeal, microbes. Alpha diversity was lower in IPF in PBAL compared to COPD (p = 0.03) and controls (p = 0.01), as well as in rPSB compared to COPD (p = 0.02) and controls (p = 0.04). Phylogenetic beta diversity showed significantly more similarity for IPF compared with COPD and controls. There were no significant correlations between alpha diversity and AMPs. Conclusions IPF differed in microbial diversity from COPD and controls, accompanied by differences in antimicrobial peptides. Beta diversity similarity between OW and PBAL in IPF may indicate that microaspiration contributes to changes in its microbiome.