Gastric juice microbiota in pediatric chronic gastritis that clinically tested positive and negative for Helicobacter pylori.

Purpose: Helicobacter pylori (HP) infection is an identified risk factor for pediatric chronic gastritis (PCG), but its impact on gastric juice microbiota (GJM) remains to be further elucidated in PCG. This study aimed to analyze and compare the microbial communities and microbial interactive networks of GJM in PCG that clinically tested positive and negative for HP (HP+ and HP-, respectively). Methods: A total of 45 PCG patients aged from 6 to 16 years were recruited, including 20 HP+ and 25 HP- patients tested by culture and rapid urease test. Gastric juice samples were collected from these PCG patients and subjected to high-throughput amplicon sequencing and subsequent analysis of 16S rRNA genes. Results: While no significant change in alpha diversity, significant differences in beta diversity were observed between HP+ and HP- PCG. At the genus level, Streptococcus, Helicobacter, and Granulicatella were significantly enriched in HP+ PCG, whereas Campylobacter and Absconditabacteriales (SR1) were significantly enriched in HP- PCG. Network analysis showed that Streptococcus was the only genus positively correlated with Helicobacter (r = 0.497) in the GJM network of overall PCG. Moreover, compared to HP- PCG, HP+ PCG showed a reduction in microbial network connectivity in GJM. Netshift analysis identified driver microbes including Streptococcus and other four genera, which substantially contributed to the GJM network transition from HP- PCG to HP+ PCG. Furthermore, Predicted GJM function analysis indicated up-regulated pathways related to the metabolism of nucleotides, carbohydrates, and L-Lysine, the urea cycle, as well as endotoxin peptidoglycan biosynthesis and maturation in HP+ PCG. Conclusion: GJM in HP+ PCG exhibited dramatically altered beta diversity, taxonomic structure, and function, with reduced microbial network connectivity, which could be involved in the disease etiology.

Host A-to-I RNA editing signatures in intracellular bacterial and single-strand RNA viral infections.

Background: Microbial infection is accompanied by remodeling of the host transcriptome. Involvement of A-to-I RNA editing has been reported during viral infection but remains to be elucidated during intracellular bacterial infections. Results: Herein we analyzed A-to-I RNA editing during intracellular bacterial infections based on 18 RNA-Seq datasets of 210 mouse samples involving 7 tissue types and 8 intracellular bacterial pathogens (IBPs), and identified a consensus signature of RNA editing for IBP infections, mainly involving neutrophil-mediated innate immunity and lipid metabolism. Further comparison of host RNA editing patterns revealed remarkable similarities between pneumonia caused by IBPs and single-strand RNA (ssRNA) viruses, such as altered editing enzyme expression, editing site numbers, and levels. In addition, functional enrichment analysis of genes with RNA editing highlighted that the Rab GTPase family played a common and vital role in the host immune response to IBP and ssRNA viral infections, which was indicated by the consistent up-regulated RNA editing of Ras-related protein Rab27a. Nevertheless, dramatic differences between IBP and viral infections were also observed, and clearly distinguished the two types of intracellular infections. Conclusion: Our study showed transcriptome-wide host A-to-I RNA editing alteration during IBP and ssRNA viral infections. By identifying and comparing consensus signatures of host A-to-I RNA editing, our analysis implicates the importance of host A-to-I RNA editing during these infections and provides new insights into the diagnosis and treatment of infectious diseases.

Repeated Winning and Losing Experiences in Chronic Social Conflicts Are Linked to RNA Editing Pattern Difference.

Winner-loser effects influence subsequent agonistic interactions between conspecifics. Previous winning experiences could strengthen future aggression and increase the chance of winning the next agonistic interaction, while previous losing experiences could have the opposite effect. Although the role of A-to-I RNA editing has been recently implicated in chronic social defeat stress and aggressive behavior, it remains to be further elucidated in chronic social conflicts in agonistic interactions, especially in the repeated aggression (winners) and repeated defeat (losers) resulted from these conflicts. In the current study, transcriptome-wide A-to-I RNA editing in the dorsal striatum was investigated in a mouse model of chronic social conflicts, and compared between mice repeatedly winning and losing daily agonistic interactions. Our analysis identified 622 A-to-I RNA editing sites in the mouse dorsal striatum, with 23 to be differentially edited in 22 genes, most of which had been previously associated with neurological, psychiatric, or immune disorders. Among these differential RNA editing (DRE) sites four missense variants were observed in neuroligin 2 (Nlgn2), Cdc42 guanine nucleotide exchange factor 9 (Arhgef9) BLCAP apoptosis inducing factor (Blcap), and cytoplasmic FMR1 interacting protein 2 (Cyfip2), as well as two noncoding RNA sites in small nucleolar RNA host gene 11 (Snhg11) and the maternally expressed 3 (Meg3) gene. Moreover, significant changes were observed in gene functions and pathways enriched by genes with A-to-I RNA editing in losers and especially winners compared to controls. Our results demonstrate that repeated winning and losing experiences in chronic social conflicts are linked to A-to-I RNA editing pattern difference, underlining its role in the molecular mechanism of agonistic interactions between conspecifics.

Brain Epitranscriptomic Analysis Revealed Altered A-to-I RNA Editing in Septic Patients.

Recent studies suggest that RNA editing is associated with impaired brain function and neurological and psychiatric disorders. However, the role of A-to-I RNA editing during sepsis-associated encephalopathy (SAE) remains unclear. In this study, we analyzed adenosine-to-inosine (A-to-I) RNA editing in postmortem brain tissues from septic patients and controls. A total of 3024 high-confidence A-to-I RNA editing sites were identified. In sepsis, there were fewer A-to-I RNA editing genes and editing sites than in controls. Among all A-to-I RNA editing sites, 42 genes showed significantly differential RNA editing, with 23 downregulated and 19 upregulated in sepsis compared to controls. Notably, more than 50% of these genes were highly expressed in the brain and potentially related to neurological diseases. Notably, cis-regulatory analysis showed that the level of RNA editing in six differentially edited genes was significantly correlated with the gene expression, including HAUS augmin-like complex subunit 2 (HAUS2), protein phosphatase 3 catalytic subunit beta (PPP3CB), hook microtubule tethering protein 3 (HOOK3), CUB and Sushi multiple domains 1 (CSMD1), methyltransferase-like 7A (METTL7A), and kinesin light chain 2 (KLC2). Furthermore, enrichment analysis showed that fewer gene functions and KEGG pathways were enriched by edited genes in sepsis compared to controls. These results revealed alteration of A-to-I RNA editing in the human brain associated with sepsis, thus providing an important basis for understanding its role in neuropathology in SAE.

Transplantation of Gut Microbiota From High-Fat-Diet-Tolerant Cynomolgus Monkeys Alleviates Hyperlipidemia and Hepatic Steatosis in Rats.

Emerging evidence has been reported to support the involvement of the gut microbiota in the host's blood lipid and hyperlipidemia (HLP). However, there remains unexplained variation in the host's blood lipid phenotype. Herein a nonhuman primate HLP model was established in cynomolgus monkeys fed a high-fat diet (HFD) for 19 months. At month 19%, 60% (3/5) of the HFD monkeys developed HLP, but surprisingly 40% of them (2/5) exhibited strong tolerance to the HFD (HFD-T) with their blood lipid profiles returning to normal levels. Metagenomic analysis was used to investigate the compositional changes in the gut microbiota in these monkeys. Furthermore, the relative abundance of Megasphaera remarkably increased and became the dominant gut microbe in HFD-T monkeys. A validation experiment showed that transplantation of fecal microbiota from HFD-T monkeys reduced the blood lipid levels and hepatic steatosis in HLP rats. Furthermore, the relative abundance of Megasphaera significantly increased in rats receiving transplantation, confirming the successful colonization of the microbe in the host and its correlation with the change of the host's blood lipid profiles. Our results thus suggested a potentially pivotal lipid-lowering role of Megasphaera in the gut microbiota, which could contribute to the variation in the host's blood lipid phenotype.