Immunity-related GTPase IRGM at the intersection of autophagy, inflammation, and tumorigenesis.

The human immunity-related GTPase M (IRGM) is a GTP-binding protein that regulates selective autophagy including xenophagy and mitophagy. IRGM impacts autophagy by (1) affecting mitochondrial fusion and fission, (2) promoting the co-assembly of ULK1 and Beclin 1, (3) enhancing Beclin 1 interacting partners (AMBRA1, ATG14L1, and UVRAG), (4) interacting with other key proteins (ATG16L1, p62, NOD2, cGAS, TLR3, and RIG-I), and (5) regulating lysosomal biogenesis. IRGM also negatively regulates NLRP3 inflammasome formation and therefore, maturation of the important pro-inflammatory cytokine IL-1ß, impacting inflammation and pyroptosis. Ultimately, this affords protection against chronic inflammatory diseases. Importantly, ten IRGM polymorphisms (rs4859843, rs4859846, rs4958842, rs4958847, rs1000113, rs10051924, rs10065172, rs11747270, rs13361189, and rs72553867) have been associated with human inflammatory disorders including cancer, which suggests that these genetic variants are functionally relevant to the autophagic and inflammatory responses. The current review contextualizes IRGM, its modulation of autophagy, and inflammation, and emphasizes the role of IRGM as a cross point of immunity and tumorigenesis.

Diet and risk of Barrett's oesophagus: Melbourne collaborative cohort study.

Barrett's oesophagus (BE) is the precursor of oesophageal adenocarcinoma, which has become the most common type of oesophageal cancer in many Western populations. Existing evidence on diet and risk of BE predominantly comes from case-control studies, which are subject to recall bias in measurement of diet. We aimed to investigate the potential effect of diet, including macronutrients, carotenoids, food groups, specific food items, beverages and dietary scores, on risk of BE in over 20 000 participants of the Melbourne Collaborative Cohort Study. Diet at baseline (1990-1994) was measured using a food frequency questionnaire. The outcome was BE diagnosed between baseline and follow-up (2007-2010). Logistic regression models were used to estimate OR and 95 % CI for diet in relation to risk of BE. Intakes of leafy vegetables and fruit were inversely associated with risk of BE (highest v. lowest quartile: OR = 0·59; CI: 0·38, 0·94; P-trend = 0·02 and OR = 0·58; CI: 0·37, 0·93; P-trend = 0·02 respectively), as were dietary fibre and carotenoids. Stronger associations were observed for food than the nutrients found in them. Positive associations were observed for discretionary food (OR = 1·54; CI: 0·97, 2·44; P-trend = 0·04) and total fat intake (OR per 10 g/d = 1·11; CI: 1·00, 1·23), the association for fat was less robust in sensitivity analyses. No association was observed for meat, protein, dairy products or diet scores. Diet is a potential modifiable risk factor for BE. Public health and clinical guidelines that incorporate dietary recommendations could contribute to reduction in risk of BE and, thereby, oesophageal adenocarcinoma.

Genetic variants involved in innate immunity modulate the risk of inflammatory bowel diseases in an understudied Malaysian population.

BACKGROUND AND AIM: Inflammatory bowel diseases (IBD) are chronic gastrointestinal inflammatory conditions comprising two major subtypes: Crohn's disease (CD) and ulcerative colitis (UC). The incidence of IBD is increasing in Asian countries including Malaysia. The aim of this study was to determine whether 32 single nucleotide polymorphisms (SNPs) strongly associated with IBD from genome-wide association studies, performed mainly in Caucasian populations, are associated with IBD in a Malaysian population, correlating these findings with local and systemic inflammation. METHODS: Selected SNPs were investigated in a Malaysian cohort comprising 36 IBD patients and 75 controls using customized matrix-assisted laser desorption ionization time-of-flight genotyping. Local mRNA and/or systemic protein levels of IL-10, IL-12, IL-22, IL-23, and TNF-α were measured in these same subjects. RESULTS: ATG16L2 rs11235667 and LINC00824 rs6651252 was significantly associated with increased CD risk while IL12B rs56167332 was a significant protective factor. Three SNPs (SBNO2 rs2024092, CARD9 rs10781499, and rs17085007 between GPR12-USP12) were significantly associated with increased UC risk while NKX2-3 rs4409764 was a significant protective factor. After adjusting for age, gender, and ethnicity, SBNO2 rs2024092, ATG16L2 rs11235667, CARD9 rs10781499, and LINC00824 rs6651252 remained associated with IBD. Interestingly, the risk alleles of IL10 rs3024505, CARD9 rs1078149, and IL12 rs6556412 were associated with higher levels of IL-10, IL-22, and IL-23 in these same subjects, respectively. CONCLUSIONS: This study identified eight SNPs associated with IBD and/or its subtypes in the Malaysia population, significantly advancing our understanding of the genetic contribution to IBD in this understudied population. Three of these SNPs modulated relevant cytokine levels and thus, may directly contribute to IBD pathogenesis.

Is there an association between the vaginal microbiome and first trimester miscarriage? A prospective observational study.

AIM: To examine whether there are differences in the vaginal microbiome of women who miscarry compared to those who have normal pregnancy outcomes. METHODS: Prospective observational study conducted at the Canberra Hospital, Australia, with 24 participant women in the first trimester of pregnancy. The vaginal microbiomes of the 24 women were characterized using sequencing analysis of the V4 region of the 16S rRNA gene employing an Illumina MiSeq instrument with QIAGEN reagents. Vaginal microbiome data were correlated with pregnancy clinical metadata. RESULTS: Ordination plots showed differences in the composition of microbiomes of women who miscarried and controls. In nulliparous women, Lactobacillus crispatus was the dominant bacterium in 50% of women. Lactobacillus iners was the dominant bacterium in 50% of women with a history of prior miscarriage and a miscarriage in the study compared to 15% (p = 0.011) in those with no history of miscarriage and no miscarriage in the study. There were significant differences in the number of operational taxonomic units and the richness of the microbiomes of women who miscarried compared to those who delivered at term. Eight taxa were found in different relative abundances in both groups of women. CONCLUSIONS: The study indicated that the composition of the vaginal microbiome varies with pregnancy history. Also, there was a significant difference in the vaginal microbiomes between women who suffered miscarriage and those who continued to term delivery both in the overall microbiome populations and in the abundances of individual taxa.

Gut Microbiome Analysis Identifies Potential Etiological Factors in Acute Gastroenteritis.

The morbidity and mortality resulting from acute gastroenteritis and associated chronic sequelae represent a substantial burden on health care systems worldwide. Few studies have investigated changes in the gut microbiome following an episode of acute gastroenteritis. By using nondirected 16S rRNA gene amplicon sequencing, the fecal microbiota of 475 patients with acute gastroenteritis was examined. Patient age was correlated with the overall microbial composition, with a decrease in the abundance of Faecalibacterium being observed in older patients. We observed the emergence of a potential Escherichia-Shigella-dominated enterotype in a subset of patients, and this enterotype was predicted to be more proinflammatory than the other common enterotypes, with the latter being dominated by Bacteroides or Faecalibacterium The increased abundance of Escherichia-Shigella did not appear to be associated with infection with an agent of a similar sequence similarity. Stool color and consistency were associated with the diversity and composition of the microbiome, with deviations from the norm (not brown and solid) showing increases in the abundances of bacteria such as Escherichia-Shigella and Veillonella Analysis of enriched outliers within the data identified a range of genera previously associated with gastrointestinal diseases, including Treponema, Proteus, Capnocytophaga, Arcobacter, Campylobacter, Haemophilus, Aeromonas, and Pseudomonas Our data represent the first in-depth analysis of gut microbiota in acute gastroenteritis. Phenotypic changes in stool color and consistency were associated with specific changes in the microbiota. Enriched bacterial taxa were detected in cases where no causative agent was identified by using routine diagnostic tests, suggesting that in the future, microbiome analyses may be utilized to improve diagnostics.

Dual role of Helicobacter and Campylobacter species in IBD: a systematic review and meta-analysis.

OBJECTIVE: To conduct a comprehensive global systematic review and meta-analysis on the association between Helicobacter pylori infection and IBD. As bacterial antigen cross-reactivity has been postulated to be involved in this association, published data on enterohepatic Helicobacter spp (EHS) and Campylobacter spp and IBD was also analysed. DESIGN: Electronic databases were searched up to July 2015 for all case-control studies on H. pylori infection/EHS/Campylobacter spp and IBD. Pooled ORs (P-OR) and 95% CIs were obtained using the random effects model. Heterogeneity, sensitivity and stratified analyses were performed. RESULTS: Analyses comprising patients with Crohn's disease (CD), UC and IBD unclassified (IBDU), showed a consistent negative association between gastric H. pylori infection and IBD (P-OR: 0.43, p value <1e-10). This association appears to be stronger in patients with CD (P-OR: 0.38, p value <1e-10) and IBDU (P-OR: 0.43, p value=0.008) than UC (P-OR: 0.53, p value <1e-10). Stratification by age, ethnicity and medications showed significant results. In contrast to gastric H. pylori, non H. pylori-EHS (P-OR: 2.62, p value=0.001) and Campylobacter spp, in particular C. concisus (P-OR: 3.76, p value=0.006) and C. showae (P-OR: 2.39, p value=0.027), increase IBD risk. CONCLUSIONS: H. pylori infection is negatively associated with IBD regardless of ethnicity, age, H. pylori detection methods and previous use of aminosalicylates and corticosteroids. Antibiotics influenced the magnitude of this association. Closely related bacteria including EHS and Campylobacter spp increase the risk of IBD. These results infer that H. pylori might exert an immunomodulatory effect in IBD.

Global Epidemiology of Campylobacter Infection.

Campylobacter jejuni infection is one of the most widespread infectious diseases of the last century. The incidence and prevalence of campylobacteriosis have increased in both developed and developing countries over the last 10 years. The dramatic increase in North America, Europe, and Australia is alarming, and data from parts of Africa, Asia, and the Middle East indicate that campylobacteriosis is endemic in these areas, especially in children. In addition to C. jejuni, there is increasing recognition of the clinical importance of emerging Campylobacter species, including Campylobacter concisus and Campylobacter ureolyticus. Poultry is a major reservoir and source of transmission of campylobacteriosis to humans. Other risk factors include consumption of animal products and water, contact with animals, and international travel. Strategic implementation of multifaceted biocontrol measures to reduce the transmission of this group of pathogens is paramount for public health. Overall, campylobacteriosis is still one of the most important infectious diseases that is likely to challenge global health in the years to come. This review provides a comprehensive overview of the global epidemiology, transmission, and clinical relevance of Campylobacter infection.

Autophagy in Helicobacter pylori Infection and Related Gastric Cancer.

BACKGROUND: Autophagy, a degradation pathway in which cytoplasmic content is engulfed and degraded by lysosomal hydrolases, plays a pivotal role in infection and inflammation. Given that defects in autophagy lead to increased susceptibility to infection, we investigated the role of autophagy in Helicobacter pylori-related gastric cancer (GC). MATERIALS AND METHODS: Gene expression of 84 molecules was examined through quantitative real-time PCR in gastric epithelial cells (AGS) and macrophages (THP-1) upon exposure to H. pylori GC026 (GC) and 26695 (gastritis). Further, ATG16L1 rs2241880, IRGM rs13361189, and IRGM rs4958847, polymorphisms that have been investigated in relation to H. pylori infection or GC in Caucasians, were detected by MALDI-TOF mass spectrometry in 304 ethnic Chinese (86 noncardia GC cases/218 functional dyspepsia controls). RESULTS: Gene expression analyses showed twenty-eight molecules involved in vesicle nucleation, elongation, and maturation to be significantly down-regulated in H. pylori GC026-challenged AGS cells. Further, core autophagy proteins and autophagy regulators were differentially expressed in H. pylori-challenged THP-1-derived macrophages. Analyses of the selected polymorphisms showed that ATG16L1 rs2241880 increased the risk of GC (OR: 2.38, 95% CI: 1.34-4.24) and H. pylori infection (OR: 1.49, 95% CI: 1.02-2.16) while IRGM rs4958847 decreased GC risk (OR: 0.26, 95% CI: 0.09-0.74) in ethnic Chinese, these effect sizes being especially strong in H. pylori-infected individuals (ATG16L1 rs2241880 and IRGM rs13361189). CONCLUSIONS: Our findings indicate that highly virulent H. pylori strains markedly modulate autophagy in the host cell. Further, for the first time, autophagy polymorphisms were associated with GC in Chinese, a high GC-risk population.

ATG16L1 rs2241880/T300A increases susceptibility to perianal Crohn's disease: An updated meta-analysis on inflammatory bowel disease risk and clinical outcomes.

BACKGROUND: ATG16L1 plays a fundamental role in the degradative intracellular pathway known as autophagy, being a mediator of inflammation and microbial homeostasis. The variant rs2241880 can diminish these capabilities, potentially contributing to inflammatory bowel disease (IBD) pathogenesis. OBJECTIVES: To perform an updated meta-analysis on the association between ATG16L1 rs2241880 and IBD susceptibility by exploring the impact of age, ethnicity, and geography. Moreover, to investigate the association between rs2241880 and clinical features. METHODS: Literature searches up until September 2022 across 7 electronic public databases were performed for all case-control studies on ATG16L1 rs2241880 and IBD. Pooled odds ratios (ORP ) and 95% CI were calculated under the random effects model. RESULTS: Our analyses included a total of 30,606 IBD patients, comprising 21,270 Crohn's disease (CD) and 9336 ulcerative colitis (UC) patients, and 33,329 controls. ATG16L1 rs2241880 was significantly associated with CD susceptibility, where the A allele was protective (ORP : 0.74, 95% CI: 0.72-0.77, p-value: <0.001), while the G allele was a risk factor (ORP : 1.23, 95% CI: 1.09-1.39, p-value: 0.001), depending on the minor allele frequencies observed in this multi-ancestry study sample. rs2241880 was predominantly relevant in Caucasians from North America and Europe, and in Latin American populations. Importantly, CD patients harbouring the G allele were significantly more predisposed to perianal disease (ORP : 1.21, 95% CI: 1.07-1.38, p-value: 0.003). CONCLUSIONS: ATG16L1 rs2241880 (G allele) is a consistent risk factor for IBD in Caucasian cohorts and influences clinical outcomes. As its role in non-Caucasian populations remains ambiguous, further studies in under-reported populations are necessary.

Profiling the colonic mucosal response to fecal microbiota transplantation identifies a role for GBP5 in colitis in humans and mice.

Host molecular responses to fecal microbiota transplantation (FMT) in ulcerative colitis are not well understood. Here, we profile the human colonic mucosal transcriptome prior to and following FMT or placebo to identify molecules regulated during disease remission. FMT alters the transcriptome above the effect of placebo (n = 75 vs 3 genes, q < 0.05), including modulation of structural, metabolic and inflammatory pathways. This response is attributed to responders with no consistency observed in non-responders. Regulated pathways in responders include tight junctions, calcium signalling and xenobiotic metabolism. Genes significantly regulated longitudinally in responders post-FMT could discriminate them from responders and non-responders at baseline and non-responders post-FMT, with GBP5 and IRF4 downregulation being associated with remission. Female mice with a deletion of GBP5 are more resistant to developing colitis than their wild-type littermates, showing higher colonic IRF4 phosphorylation. The colonic mucosal response discriminates UC remission following FMT, with GBP5 playing a detrimental role in colitis.

The role of ATG16L2 in autophagy and disease.

Macroautophagy/autophagy, a fundamental cell process for nutrient recycling and defense against pathogens (termed xenophagy), is crucial to human health. ATG16L2 (autophagy related 16 like 2) is an autophagic protein and a paralog of ATG16L1. Both proteins are implicated in similar diseases such as cancer and other chronic diseases; however, most autophagy studies to date have primarily focused on the function of ATG16L1, with ATG16L2 remaining uncharacterized and understudied. Overexpression of ATG16L2 has been reported in various cancers including colorectal, gastric, and prostate carcinomas, whereas altered methylation of ATG16L2 has been associated with lung cancer formation and poorer response to therapy in leukemia. In addition, ATG16L2 polymorphisms have been implicated in a range of other diseases including inflammatory bowel diseases and neurodegenerative disorders. Despite this likely role in human health, the function of this enigmatic protein in autophagy remains unknown. Here, we review current studies on ATG16L2 and collate evidence that suggests that this protein is a potential modulator of autophagy as well as the implications this has on pathogenesis.Abbreviations: ATG5: autophagy related 5; ATG12: autophagy related 12; ATG16L1: autophagy related 16 like 1; ATG16L2: autophagy related 16 like 2; CD: Crohn disease; IBD: inflammatory bowel diseases; IRGM: immunity related GTPase M; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; PE: phosphatidylethanolamine; RB1CC1: RB1 inducible coiled-coil 1; SLE: systemic lupus erythematosus; WIPI2B: WD repeat domain, phosphoinositide interacting 2B.

Changes to the upper gastrointestinal microbiotas of children with reflux oesophagitis and oesophageal metaplasia.

Little is known of the relationships among paediatric upper gastrointestinal microbiotas, and the impact of medication use and disease on their diversity. Here, we investigated the diversity of three microbiotas in the upper gastrointestinal tract of paediatric patients in relation to each other and to host factors. Oral, oesophageal and gastric microbiotas from a prospective paediatric cohort (n=54) were profiled using the 16S rRNA gene and ITS2 amplicon sequencing. 16S rRNA gene amplicon sequencing of oesophageal biopsies from a retrospective paediatric cohort (n=96) and shotgun metagenomics data from oesophageal brushings (n=88) were employed for genomic signature validation. Bacterial diversity and composition showed substantial differences across oral, oesophageal and gastric fluid samples that were not replicated for fungi, and the presence of reflux led to increased homogeneity in the bacterial component of these three microbiotas. The oral and oesophageal microbiotas were associated with age, sex, history of oesophageal atresia and presence of oesophageal metaplasia, with the latter characterized by Prevotella enrichment. Proton pump inhibitor use was associated with increased oral bacterial richness in the gastric fluid, and this correlated with increased levels of gastric pro-inflammatory cytokines. Profiling of oesophageal biopsies from a retrospective paediatric cohort confirmed an increased Prevotella prevalence in samples with metaplasia. Analysis of metagenome-derived oesophageal Prevotella melaninogenica genomes identified strain-specific features that were significantly increased in prevalence in samples with metaplasia. Prevotella enrichment is a signature associated with paediatric oesophageal metaplasia, and proton pump inhibitor use substantially alters the paediatric gastric microenvironment.

dRNASb: a systems biology approach to decipher dynamics of host-pathogen interactions using temporal dual RNA-seq data.

Infection triggers a dynamic cascade of reciprocal events between host and pathogen wherein the host activates complex mechanisms to recognise and kill pathogens while the pathogen often adjusts its virulence and fitness to avoid eradication by the host. The interaction between the pathogen and the host results in large-scale changes in gene expression in both organisms. Dual RNA-seq, the simultaneous detection of host and pathogen transcripts, has become a leading approach to unravelling complex molecular interactions between the host and the pathogen and is particularly informative for intracellular organisms. The amount of in vitro and in vivo dual RNA-seq data is rapidly growing, which demands computational pipelines to effectively analyse such data. In particular, holistic, systems-level, and temporal analyses of dual RNA-seq data are essential to enable further insights into the host-pathogen transcriptional dynamics and potential interactions. Here, we developed an integrative network-driven bioinformatics pipeline, dRNASb, a systems biology-based computational pipeline to analyse temporal transcriptional clusters, incorporate molecular interaction networks (e.g. protein-protein interactions), identify topologically and functionally key transcripts in host and pathogen, and associate host and pathogen temporal transcriptome to decipher potential between-species interactions. The pipeline is applicable to various dual RNA-seq data from different species and experimental conditions. As a case study, we applied dRNASb to analyse temporal dual RNA-seq data of Salmonella-infected human cells, which enabled us to uncover genes contributing to the infection process and their potential functions and to identify putative associations between host and pathogen genes during infection. Overall, dRNASb has the potential to identify key genes involved in bacterial growth or host defence mechanisms for future uses as therapeutic targets.

Mechanisms for the Sex-Specific Effect of H. Pylori on Risk of Gastroesophageal Reflux Disease and Barrett's Esophagus.

BACKGROUND: Mechanisms for how Helicobacter pylori infection affects risk of gastroesophageal reflux disease (GERD) and Barrett's esophagus are incompletely understood and might differ by sex. METHODS: In a case-control study nested in the Melbourne Collaborative Cohort Study with 425 GERD cases and 169 Barrett's esophagus cases (identified at 2007-2010 follow-up), we estimated sex-specific odds ratios for participants who were H. pylori seronegative versus seropositive at baseline (1990-1994). To explore possible mechanisms, we (i) compared patterns of H. pylori-induced gastritis by sex using serum pepsinogen-I and gastrin-17 data and (ii) quantified the effect of H. pylori seronegativity on Barrett's esophagus mediated by GERD using causal mediation analysis. RESULTS: For men, H. pylori seronegativity was associated with 1.69-fold [95% confidence interval (CI), 1.03-2.75] and 2.28-fold (95% CI, 1.27-4.12) higher odds of GERD and Barrett's esophagus, respectively. No association was observed for women. H. pylori-induced atrophic antral gastritis was more common in men (68%) than in women (56%; P = 0.015). For men, 5 of the 15 per 1,000 excess Barrett's esophagus risk from being seronegative were mediated by GERD. CONCLUSIONS: Men, but not women, who were H. pylori seronegative had increased risks of GERD and Barrett's esophagus. A possible explanation might be sex differences in patterns of H. pylori-induced atrophic antral gastritis, which could lead to less erosive reflux for men. Evidence of GERD mediating the effect of H. pylori on Barrett's esophagus risk among men supports this proposed mechanism. IMPACT: The findings highlight the importance of investigating sex differences in the effect of H. pylori on risk of GERD and Barrett's esophagus in future studies.

Did transmission of Helicobacter pylori from humans cause a disease outbreak in a colony of Stripe-faced Dunnarts (Sminthopsis macroura)?

Since the discovery that Helicobacter pylori causes a range of pathologies in the stomachs of infected humans, it has become apparent that Helicobacters are found in a diverse range of animal species where they are frequently associated with disease. In 2003 and 2004, there were two outbreaks of increased mortality associated with gastric bleeding and weight-loss in a captive colony of the Australian marsupial, the Stripe-faced Dunnart (Sminthopsis macroura). The presence of gastric pathology led to an investigation of potential Helicobacter pathogenesis in these animals. Histological examination revealed the presence of gastritis, and PCR analysis confirmed the presence of Helicobacter infection in the stomachs of these marsupials. Surprisingly, sequencing of 16S rRNA from these bacteria identified the species as H. pylori and PCR confirmed the strain to be positive for the important pathogenesis factor, cagA. We therefore describe, for the first time, an apparent reverse zoonotic infection of Stripe-faced Dunnarts with H. pylori. Already prone to pathological effects of stress (as experienced during breeding season), concomitant H. pylori infection appears to be a possible essential but not sufficient co-factor in prototypic gastric bleeding and weight loss in these marsupials. The Stripe-faced Dunnart could represent a new model for investigating Helicobacter-driven gastric pathology. Infections from their human handlers, specifically of H. pylori, may be a potential risk to captive colonies of marsupials.

Multi-omics of the esophageal microenvironment identifies signatures associated with progression of Barrett's esophagus.

BACKGROUND: The enrichment of Gram-negative bacteria of oral origin in the esophageal microbiome has been associated with the development of metaplasia. However, to date, no study has comprehensively assessed the relationships between the esophageal microbiome and the host. METHODS: Here, we examine the esophageal microenvironment in gastro-esophageal reflux disease and metaplasia using multi-omics strategies targeting the microbiome and host transcriptome, followed by targeted culture, comparative genomics, and host-microbial interaction studies of bacterial signatures of interest. RESULTS: Profiling of the host transcriptome from esophageal mucosal biopsies revealed profound changes during metaplasia. Importantly, five biomarkers showed consistent longitudinal changes with disease progression from reflux disease to metaplasia. We showed for the first time that the esophageal microbiome is distinct from the salivary microbiome and the enrichment of Campylobacter species as a consistent signature in disease across two independent cohorts. Shape fitting and matrix correlation identified associations between the microbiome and host transcriptome profiles, with a novel co-exclusion relationship found between Campylobacter and napsin B aspartic peptidase. Targeted culture of Campylobacter species from the same cohort revealed a subset of isolates to have a higher capacity to survive within primary human macrophages. Comparative genomic analyses showed these isolates could be differentiated by specific genomic features, one of which was validated to be associated with intracellular fitness. Screening for these Campylobacter strain-specific signatures in shotgun metagenomics data from another cohort showed an increase in prevalence with disease progression. Comparative transcriptomic analyses of primary esophageal epithelial cells exposed to the Campylobacter isolates revealed expression changes within those infected with strains with high intracellular fitness that could explain the increased likelihood of disease progression. CONCLUSIONS: We provide a comprehensive assessment of the esophageal microenvironment, identifying bacterial strain-specific signatures with high relevance to progression of metaplasia.

Detection of Helicobacteraceae in intestinal biopsies of children with Crohn's disease.

BACKGROUND: Given that members of Helicobacteraceae family colonize the intestinal mucus layer, it has been hypothesized that they may play a role in Crohn's disease. This study investigated the presence of Helicobacteraceae DNA in biopsies collected from children with Crohn's disease and controls. MATERIALS AND METHODS: The presence of Helicobacteraceae DNA was investigated in intestinal biopsies collected from 179 children undergoing colonoscopy (Crohn's disease n = 77, controls n = 102) using a Helicobacteraceae-specific PCR. RESULTS: Members of the Helicobacteraceae were detected in 32/77 children with Crohn's disease (41.5%) and 23/102 controls (22.5%). Statistical analysis showed the prevalence of Helicobacteraceae detected in patients to be significantly higher than that in controls (p = .0062). Analysis of non-pylori Helicobacteraceae showed that their prevalence was also significantly higher in patients than in controls (p = .04). Helicobacter pylori was detected in 14.0% of the biopsies across all groups. Given that all children tested were negative for gastric H. pylori, this was a surprising finding. Phylogenetic analysis of H. pylori sequences detected in the biopsies showed that the H. pylori strains identified in the patients did not group with gastric H. pylori included in the analysis, but rather with other H. pylori strains detected in the intestine, gall bladder, and liver. CONCLUSIONS: The higher prevalence of Helicobacteraceae DNA in Crohn's disease patients would suggest that members of this family may be involved in this disease. In addition, phylogenetic analysis of H. pylori strains showed that extragastric sequences clustered together, indicating that different H. pylori strains may adapt to colonize extragastric niches.

Comparison of the Genital Microbiomes of Pregnant Aboriginal and Non-aboriginal Women.

The genital microbiomes of women varies with racial background. Preterm birth and early-onset neonatal sepsis are two outcomes associated with genital infections during pregnancy. The rate of preterm birth in Aboriginal Australian mothers is high, as is the rate of early-onset sepsis in their infants. To date, no studies have been conducted to investigate genital microbiome taxa associated infection in this group of women. A prospective cohort study to characterize the vaginal and placental microbiomes of a group of these women from the Pilbara region was conducted at the Hedland Health Campus in Western Australia. Included in the study were gravidae Aboriginal (n = 23) and Non-aboriginal (n = 27) women in labor or for planned lower uterine segment Caesarean section. Employing sterile swabs, vaginal samples were obtained under sterile conditions immediately prior to vaginal delivery or planned Caesarean section; and placental samples were obtained under the same conditions during labor. Taxa present in the samples were identified by 16S rRNA amplicon sequencing (V4 region, 515F-806R). Taxon identity and abundance were established from Operational Taxonomic Unit (OTU) counts. Statistical analyses combining clinical metadata and sequencing results were employed to determine associations of taxa with racial background. The findings of this work served to enhance the current understanding of microbiota associated with health and disease in Aboriginal and Non-Aboriginal women. Differences were found between the vaginal and placental microbiomes of Aboriginal and Non-aboriginal women during pregnancy, as well as notable differences between the abundance of specific taxa in each racial group. The relative abundances of specific taxa were significantly different between participants with clinical signs of infection and those with healthy pregnancies. This work will contribute to understanding the causes of differences in rates of infection-driven preterm birth in various racial populations.

OPCML: A Promising Biomarker and Therapeutic Avenue.

Opioid-binding protein/cell adhesion molecule (OPCML) is expressed in many tissues and localizes to the plasma membrane. It is a putative tumor suppressor that acts on receptor tyrosine kinases (RTKs), influencing cell cycle arrest, apoptosis, and migration. Its expression is silenced epigenetically in cancer, inferring potential diagnostic, prognostic, and therapeutic roles.