Distinct gut microbiomes in Thai patients with colorectal polyps.

BACKGROUND: Colorectal polyps that develop via the conventional adenoma-carcinoma sequence [e.g., tubular adenoma (TA)] often progress to malignancy and are closely associated with changes in the composition of the gut microbiome. There is limited research concerning the microbial functions and gut microbiomes associated with colorectal polyps that arise through the serrated polyp pathway, such as hyperplastic polyps (HP). Exploration of microbiome alterations associated with HP and TA would improve the understanding of mechanisms by which specific microbes and their metabolic pathways contribute to colorectal carcinogenesis. AIM: To investigate gut microbiome signatures, microbial associations, and microbial functions in HP and TA patients. METHODS: Full-length 16S rRNA sequencing was used to characterize the gut microbiome in stool samples from control participants without polyps [control group (CT), n = 40], patients with HP (n = 52), and patients with TA (n = 60). Significant differences in gut microbiome composition and functional mechanisms were identified between the CT group and patients with HP or TA. Analytical techniques in this study included differential abundance analysis, co-occurrence network analysis, and differential pathway analysis. RESULTS: Colorectal cancer (CRC)-associated bacteria, including Streptococcus gallolyticus (S. gallolyticus), Bacteroides fragilis, and Clostridium symbiosum, were identified as characteristic microbial species in TA patients. Mediterraneibacter gnavus, associated with dysbiosis and gastrointestinal diseases, was significantly differentially abundant in the HP and TA groups. Functional pathway analysis revealed that HP patients exhibited enrichment in the sulfur oxidation pathway exclusively, whereas TA patients showed dominance in pathways related to secondary metabolite biosynthesis (e.g., mevalonate); S. gallolyticus was a major contributor. Co-occurrence network and dynamic network analyses revealed co-occurrence of dysbiosis-associated bacteria in HP patients, whereas TA patients exhibited co-occurrence of CRC-associated bacteria. Furthermore, the co-occurrence of SCFA-producing bacteria was lower in TA patients than HP patients. CONCLUSION: This study revealed distinct gut microbiome signatures associated with pathways of colorectal polyp development, providing insights concerning the roles of microbial species, functional pathways, and microbial interactions in colorectal carcinogenesis.

[Exploring the causality between intestinal flora and hyperplastic scars of human based on two-sample Mendelian randomization analysis].

Objective: To investigate the causality between intestinal flora and hypertrophic scars (HS) of human. Methods: This study was a study based on two-sample Mendelian randomization (TSMR) analysis. The data on intestinal flora (n=18 473) and HS (n=208 248) of human were obtained from the genome-wide association study database. Genetically variable genes at five levels (phylum, class, order, family, and genus) of known intestinal flora, i.e., single nucleotide polymorphisms (SNPs), were extracted as instrumental variables for linkage disequilibrium (LD) analysis. Human genotype-phenotype association analysis was performed using PhenoScanner V2 database to exclude SNPs unrelated to HS in intestinal flora and analyze whether the selected SNPs were weak instrumental variables. The causal relationship between intestinal flora SNPs and HS was analyzed through four methods of TSMR analysis, namely inverse variance weighted (IVW), MR-Egger regression, weighted median, and weighted mode. Scatter plots of significant results from the four aforementioned analysis methods were plotted to analyze the correlation between intestinal flora SNPs and HS. Both IVW test and MR-Egger regression test were used to assess the heterogeneity of intestinal flora SNPs, MR-Egger regression test and MR-PRESSO outlier test were used to assess the horizontal multiplicity of intestinal flora SNPs, and leave-one-out sensitivity analysis was used to determine whether HS was caused by a single SNP in the intestinal flora. Reverse TSMR analyses were performed for HS SNPs and genus Intestinimonas or genus Ruminococcus2, respectively, to detect whether there was reverse causality between them. Results: A total of 196 known intestinal flora, belonging to 9 phyla, 16 classes, 20 orders, 32 families, and 119 genera, were obtained, and multiple SNPs were obtained from each flora as instrumental variables. LD analysis showed that the SNPs of the intestinal flora were consistent with the hypothesis that genetic variation was strongly associated with exposure factors, except for rs1000888, rs12566247, and rs994794. Human genotype-phenotype association analysis showed that none of the selected SNPs after LD analysis was excluded and there were no weak instrumental variables. IVW, MR-Egger regression, weighted median, and weighted mode of TSMR analysis showed that both genus Intestinimonas and genus Ruminococcus2 were causally associated with HS. Among them, forest plots of IVW and MR-Egger regression analyses also showed that 16 SNPs (the same SNPs number of this genus below) of genus Intestinimonas and 15 SNPs (the same SNPs number of this genus below) of genus Ruminococcus2 were protective factors for HS. Further, IVW analysis showed that genus Intestinimonas SNPs (with odds ratio of 0.62, 95% confidence interval of 0.41-0.93, P<0.05) and genus Ruminococcus2 SNPs (with odds ratio of 0.62, 95% confidence interval of 0.40-0.97, P<0.05) were negatively correlated with the risk of HS. Scatter plots showed that SNPs of genus Intestinimonas and genus Ruminococcus2 were protective factors of HS. Both IVW test and MR-Egger regression test showed that SNPs of genus Intestinimonas (with Q values of 5.73 and 5.76, respectively, P>0.05) and genus Ruminococcus2 (with Q values of 13.67 and 15.61, respectively, P>0.05) were not heterogeneous. MR-Egger regression test showed that the SNPs of genus Intestinimonas and genus Ruminococcus2 had no horizontal multiplicity (with intercepts of 0.01 and 0.06, respectively, P>0.05); MR-PRESSO outlier test showed that the SNPs of genus Intestinimonas and genus Ruminococcus2 had no horizontal multiplicity (P>0.05). Leave-one-out sensitivity analysis showed that no single intestinal flora SNP drove the occurrence of HS. Reverse TSMR analysis showed no reverse causality between HS SNPs and genus Intestinimonas or genus Ruminococcus2 (with odds ratios of 1.01 and 0.99, respectively, 95% confidence intervals of 0.97-1.06 and 0.96-1.04, respectively, P>0.05). Conclusions: There is a causal relationship between intestinal flora and HS of human, in which genus Intestinimonas and genus Ruminococcus2 have a certain effect on inhibiting HS.

Paired qualitative and quantitative analysis of bacterial microcolonies in the tonsils of patients with tonsillar hyperplasia.

The discovery of bacterial microcolonies in tonsillar tissue of patients with tonsillar hyperplasia has raised the question of their role in provoking the local immune response. Tonsils collected from patients undergoing tonsillectomy were stained for three clinically relevant bacterial taxa and lymphocytes. The bacterial composition and abundance of microcolonies was investigated using a combination of laser-microdissection, amplicon sequencing and Droplet Digital polymerase chain reaction. Microcolonies were detected in most samples (32/35) with a high prevalence of Haemophilus influenzae (78% of samples). B and T cell lymphocytes were significantly higher in the epithelium adjacent to microcolonies compared to epithelium distal to microcolonies. Furthermore, significant positive and negative correlations were identified between bacterial taxa and lymphocytes. Genus Streptococcus, which includes Group A Streptococcus (traditionally described as the main pathogen of tonsillar hyperplasia), was found in low abundance in this study. These results suggest other potential pathogens may be involved in stimulating the local immune response leading to tonsillar hyperplasia.

A kinase inhibitor screen identifies signaling pathways regulating mucosal growth during otitis media.

Otitis media, the most common disease of childhood, is characterized by extensive changes in the morphology of the middle ear cavity. This includes hyperplasia of the mucosa that lines the tympanic cavity, from a simple monolayer of squamous epithelium into a greatly thickened, respiratory-type mucosa. The processes that control this response, which is critical to otitis media pathogenesis and recovery, are incompletely understood. Given the central role of protein phosphorylation in most intracellular processes, including cell proliferation and differentiation, we screened a library of kinase inhibitors targeting members of all the major families in the kinome for their ability to influence the growth of middle ear mucosal explants in vitro. Of the 160 inhibitors, 30 were found to inhibit mucosal growth, while two inhibitors enhanced tissue proliferation. The results suggest that the regulation of infection-mediated tissue growth in the ME mucosa involves multiple cellular processes that span the kinome. While some of the pathways and processes identified have been previously implicated in mucosa hyperplasia others are novel. The results were used to generate a global model of growth regulation by kinase pathways. The potential for therapeutic applications of the results are discussed.

Salmonella infection induced intestinal crypt hyperplasia through Wnt/ß-catenin pathway in chicken.

S. Pullorum is a causative agent of enteric disease of poultry with serious diarrhea. However, the detailed mechanism behind its injury to intestinal mucosa barrier, especially for intestinal stem cells, is unclear. In this study, S. Pullorum were orally administrated to 3 days old chicken to investigate the pathogenesis of S. Pullorum on intestinal mucosal barrier, especially on the proliferation of epithelial cells. We found that S. Pullorum could colonize in the cecum and invade into the liver through intestinal mucosa damage, which caused obvious pathological changes in liver and intestine and even leaded to death, as well as significant reduction of body weight. We also found that S. Pullorum infection enhanced the mRNA expression of IL-1ß and IL-6 through TLR4/MyD88 pathway, which was also further verified by the increased lipopolysaccharide (LPS) levels in serum. Furthermore, S. Pullorum increased the depth of crypt and density of PCNA+ cells significantly through the over-activation of Wnt/ß-catenin signaling pathway. The expression of intestinal stem cells markers Lgr5 and Bmi1 was also increased after S. Pullorum infection to support the crypt hyperplasia. In addition, we verified that S. Pullorum infection enhanced the mRNA expression of IL-1ß, TLR4, Lgr5 and Bmi1. Our study indicated that S. Pullorum infection damaged the intestinal mucosa barrier to induce diarrhea, affected the abnormal proliferation of intestinal stem cells by over-activation of Wnt/ß-catenin pathway in chicken.

Innate Immune Molecule NLRC5 Protects Mice From Helicobacter-induced Formation of Gastric Lymphoid Tissue.

BACKGROUND & AIMS: Helicobacter pylori induces strong inflammatory responses that are directed at clearing the infection, but if not controlled, these responses can be harmful to the host. We investigated the immune-regulatory effects of the innate immune molecule, nucleotide-binding oligomerization domain-like receptors (NLR) family CARD domain-containing 5 (NLRC5), in patients and mice with Helicobacter infection. METHODS: We obtained gastric biopsies from 30 patients in Australia. We performed studies with mice that lack NLRC5 in the myeloid linage (Nlrc5møKO) and mice without Nlrc5 gene disruption (controls). Some mice were gavaged with H pylori SS1 or Helicobacter felis; 3 months later, stomachs, spleens, and sera were collected, along with macrophages derived from bone marrow. Human and mouse gastric tissues and mouse macrophages were analyzed by histology, immunohistochemistry, immunoblots, and quantitative polymerase chain reaction. THP-1 cells (human macrophages, controls) and NLRC5-/- THP-1 cells (generated by CRISPR-Cas9 gene editing) were incubated with Helicobacter and gene expression and production of cytokines were analyzed. RESULTS: Levels of NLRC5 messenger RNA were significantly increased in gastric tissues from patients with H pylori infection, compared with patients without infection (P < .01), and correlated with gastritis severity (P < .05). H pylori bacteria induced significantly higher levels of chemokine and cytokine production by NLRC5-/- THP-1 macrophages than by control THP-1 cells (P < .05). After 3 months of infection with H felis, Nlrc5mø-KO mice developed gastric hyperplasia (P < .0001), splenomegaly (P < .0001), and increased serum antibody titers (P < .01), whereas control mice did not. Nlrc5mø-KO mice with chronic H felis infection had increased numbers of gastric B-cell follicles expressing CD19 (P < .0001); these follicles had features of mucosa-associated lymphoid tissue lymphoma. We identified B-cell-activating factor as a protein that promoted B-cell hyperproliferation in Nlrc5mø-KO mice. CONCLUSIONS: NLRC5 is a negative regulator of gastric inflammation and mucosal lymphoid formation in response to Helicobacter infection. Aberrant NLRC5 signaling in macrophages can promote B-cell lymphomagenesis during chronic Helicobacter infection.

Dermatologic manifestations associated with electronic cigarette use.

BACKGROUND: Electronic cigarette use continues to rise, yet there are no reviews summarizing dermatologic manifestations associated with electronic cigarettes in the literature. OBJECTIVE: To review the literature regarding cutaneous manifestations associated with electronic cigarette use and increase awareness of side effects associated with this rapidly developing public health epidemic. METHODS: The PubMed database was searched for related literature. All studies involving the effects of electronic cigarette use on the skin or mucosa were obtained and reviewed for evidence. RESULTS: Contact dermatitis, thermal injuries, and oral mucosal lesions have been reported with the use of electronic cigarettes. LIMITATIONS: The conclusions presented in individual case reports or series are not based on randomized controlled trials. CONCLUSION: Electronic cigarettes can present with harmful dermatologic manifestations.

Loss of Tight Junction Protein Claudin 18 Promotes Progressive Neoplasia Development in Mouse Stomach.

BACKGROUND & AIMS: Loss of claudin 18 (CLDN18), a membrane-spanning tight junction protein, occurs during early stages of development of gastric cancer and associates with shorter survival times of patients. We investigated whether loss of CLDN18 occurs in mice that develop intraepithelial neoplasia with invasive glands due to infection with Helicobacter pylori, and whether loss is sufficient to promote the development of similar lesions in mice with or without H pylori infection. METHODS: We performed immunohistochemical analyses in levels of CLDN18 in archived tissues from B6:129 mice infected with H pylori for 6 to 15 months. We analyzed gastric tissues from B6:129S5-Cldn18tm1Lex/Mmucd mice, in which the CLDN18 gene was disrupted in gastric tissues (CLDN18-knockout mice), or from control mice with a full-length CLDN18 gene (CLDN18+/+; B6:129S5/SvEvBrd) or heterozygous disruption of CLDN18 (CLDN18+/-; B6:129S5/SvEvBrd) that were infected with H pylori SS1 or PMSS1 at 6 weeks of age and tissues collected for analysis at 20 and 30 weeks after infection. Tissues from CLDN18-knockout mice and control mice with full-length CLDN18 gene expression were also analyzed without infection at 7 weeks and 2 years after birth. Tissues from control and CLDN18-knockout mice were analyzed by electron microscopy, stained by conventional methods and analyzed for histopathology, prepared by laser capture microdissection and analyzed by RNAseq, and immunostained for lineage markers, proliferation markers, and stem cell markers and analyzed by super-resolution or conventional confocal microscopy. RESULTS: CLDN18 had a basolateral rather than apical tight junction localization in gastric epithelial cells. B6:129 mice infected with H pylori, which developed intraepithelial neoplasia with invasive glands, had increasing levels of CLDN18 loss over time compared with uninfected mice. In B6:129 mice infected with H pylori compared with uninfected mice, CLDN18 was first lost from most gastric glands followed by disrupted and reduced expression in the gastric neck and in surface cells. Gastric tissues from CLDN18-knockout mice had low levels of inflammation but increased cell proliferation, expressed markers of intestinalized proliferative spasmolytic polypeptide-expressing metaplasia, and had defects in signal transduction pathways including p53 and STAT signaling by 7 weeks after birth compared with full-length CLDN18 gene control mice. By 20 to 30 weeks after birth, gastric tissues from uninfected CLDN18-knockout mice developed intraepithelial neoplasia that invaded the submucosa; by 2 years, gastric tissues contained large and focally dysplastic polypoid tumors with invasive glands that invaded the serosa. CONCLUSIONS: H pylori infection of B6:129 mice reduced the expression of CLDN18 early in gastric cancer progression, similar to previous observations from human gastric tissues. CLDN18 regulates cell lineage differentiation and cellular signaling in mouse stomach; CLDN18-knockout mice develop intraepithelial neoplasia and then large and focally dysplastic polypoid tumors in the absence of H pylori infection.

[THE CONDITION OF THE CERVIX IN WOMEN LIVING IN OIL AND GAS BEARING AREAS].

The aim of the study was to determine the influence of oil products on the development of cervical pathology in women living in oil and gas bearing areas. A retro and prospective study of 300 women was conducted, of which 150 studied - Temir district (main group) and 150 women of Khobdinsky district (control group). It was revealed that a complex of unfavorable environmental factors affecting the body of women living in the oil and gas bearing area leads to deterioration of gynecological health and development of the precancerous process of the cervix: in women of the main group, under constant exposure to harmful factors, significantly more often than in women in the control group reveals precancerous conditions of the cervix of varying severity -28 (18.6%) and 9 (6%). Vaginal contents in women of the main group are characterized by significant disturbances in the microbial flora, which is manifested by a significant increase in the number of strict anaerobic bacteria, 69-46% and 31-20.6%, as compared with the control group. The increased generation of anaerobes is accompanied by a decrease in the frequency of lactobacilli, in particular lactobacilli, which in turn can lead to a disruption of the normal epithelization of the cervix.

A potential role for staphylococcal and streptococcal superantigens in driving skewing of TCR Vß subsets in tonsillar hyperplasia.

The TCR Vß repertoire from patients with recurrent tonsillitis and/or tonsillar hyperplasia was examined to determine whether the TCR Vß composition is suggestive of local superantigen activity and if so, whether it is associated with the presence of superantigen producing bacteria. Tonsil specimens were cultured aerobically to allow identification and isolation of the bacterial pathogens Staphylococcus aureus and Group A Streptococcus. TCR Vß subset analysis of tonsil leucocytes was performed by flow cytometry. The superantigenic potential of tonsil S. aureus isolates was determined by multiplex PCR and a T-cell mitogenicity assay. Tonsils were collected from 40 patients who were predominantly pre-school-aged children undergoing surgery for either recurrent tonsillitis or tonsillar hyperplasia causing obstructive sleep apnoea. S. aureus was cultured from 23/40 and Group A Streptococcus from 5/40 patients. Both CD4+ and CD8+ TCR Vß populations were skewed in 17/40 patients. Twelve of these had recurrent tonsillitis of whom 9 also harboured S. aureus. Characterisation of tonsillar S. aureus isolates revealed that many contained genes for one or more potent superantigens and detection of these genes was associated with in vitro mitogenic activity. Skewing of the tonsillar TCR Vß repertoire was observed at high frequency and was most commonly associated with the presence of S. aureus. Many S. aureus isolates were mitogenic suggesting that they have a potential for local impact on the function of tonsil T cell populations. These results suggest the possibility that anti-staphylococcal antibiotics may be an effective treatment option for some patients.

Comprehensive microbiome analysis of tonsillar crypts in IgA nephropathy.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the most prevalent primary chronic glomerular disease, in which the mucosal immune response elicited particularly in the tonsils or intestine has been estimated to be involved in the development of the disease. To explore the relationship between IgAN and bacterial flora in the tonsils, we conducted a comprehensive microbiome analysis. METHODS: We enrolled 48 IgAN patients, 21 recurrent tonsillitis (RT) patients without urine abnormalities and 30 children with tonsillar hyperplasia (TH) who had undergone tonsillectomy previously. Genomic DNA from tonsillar crypts of each patient was extracted, and V4 regions of the 16S ribosomal RNA gene were amplified and analysed using a high-throughput multiplexed sequencing approach. Differences in genus composition among the three study groups were statistically analysed by permutational multivariate analysis of variance and visualized by principal component analysis (PCA). RESULTS: Substantial diversity in bacterial composition was detected in each sample. Prevotella spp., Fusobacterium spp., Sphingomonas spp. and Treponema spp. were predominant in IgAN patients. The percentage of abundance of Prevotella spp., Haemophilus spp., Porphyromonas spp. and Treponema spp. in IgAN patients was significantly different from that in TH patients. However, there was no significant difference in the percentage of abundance of any bacterial genus between IgAN and RT patients. PCA did not distinguish IgAN from RT, although it discriminated TH. No significant differences in microbiome composition among the groups of IgAN patients according to clinicopathological parameters were observed. CONCLUSIONS: Similar patterns of bacteria are present in tonsillar crypts of both IgAN and RT patients, suggesting that the host response to these bacteria might be important in the development of IgAN.

Gastric polyps diagnosed by double-contrast upper gastrointestinal barium X-ray radiography mostly arise from the Helicobacter pylori-negative stomach with low risk of gastric cancer in Japan.

BACKGROUND: Double-contrast upper gastrointestinal barium X-ray radiography (UGI-XR) is a method broadly used for gastric cancer screening in Japan. Gastric polyp is one of the most frequent findings detected by UGI-XR, but how to handle it remains controversial. METHODS: Gastric polyps of the 17,264 generally healthy subjects in Japan who underwent UGI-XR or upper gastrointestinal endoscopy (UGI-ES) in 2010 were analyzed. RESULTS: Of the 6,433 UGI-XR examinees (3,405 men and 3,028 women, 47.4 ± 9.0 years old), gastric polyps were detected in 464 men (13.6 %) and 733 women (24.2 %) and were predominantly developed on the non-atrophic gastric mucosa (p < 0.0001). Multiple logistic regression analysis showed that the presence of gastric polyps has significant association with lower value of serum anti-Helicobacter pylori IgG titer, female gender, lighter smoking habit, older age, and normal range of body mass index (≥18.5 and <25), but not with drinking or serum pepsinogen I/II ratio. During the 3-year follow-up, gastric cancer occurred in 7 subjects (0.11 %), but none of them had gastric polyps at the beginning of the follow-up period. Of the 2,722 subjects with gastric polyps among the 10,831 UGI-ES examinees in the same period, 2,446 (89.9 %) had fundic, 267 (9.8 %) had hyperplastic, and 9 (0.3 %) had adenomatous/cancerous polyps. CONCLUSIONS: Gastric polyps diagnosed by UGI-XR predominantly arise on the Helicobacter pylori-negative gastric mucosa with a low risk of gastric cancer in Japan. In the prospective observation, none of the UGI-XR examinees with gastric polyps developed gastric cancer for at least 3 years subsequently.

Virulence factors enhance Citrobacter rodentium expansion through aerobic respiration.

Citrobacter rodentium uses a type III secretion system (T3SS) to induce colonic crypt hyperplasia in mice, thereby gaining an edge during its competition with the gut microbiota through an unknown mechanism. Here, we show that by triggering colonic crypt hyperplasia, the C. rodentium T3SS induced an excessive expansion of undifferentiated Ki67-positive epithelial cells, which increased oxygenation of the mucosal surface and drove an aerobic C. rodentium expansion in the colon. Treatment of mice with the γ-secretase inhibitor dibenzazepine to diminish Notch-driven colonic crypt hyperplasia curtailed the fitness advantage conferred by aerobic respiration during C. rodentium infection. We conclude that C. rodentium uses its T3SS to induce histopathological lesions that generate an intestinal microenvironment in which growth of the pathogen is fueled by aerobic respiration.

Oral candidiasis.

Oral candidiasis (OC) is a common fungal disease encountered in dermatology, most commonly caused by an overgrowth of Candida albicans in the mouth. Although thrush is a well-recognized presentation of OC, it behooves clinicians to be aware of the many other presentations of this disease and how to accurately diagnose and manage these cases. The clinical presentations of OC can be broadly classified as white or erythematous candidiasis, with various subtypes in each category. The treatments include appropriate oral hygiene, topical agents, and systemic medications. This review focuses on the various clinical presentations of OC and treatment options.

Prevalence of Helicobacter pylori in Gastric Hyperplastic Polyps.

Hyperplastic polyps of the stomach are routinely encountered during upper endoscopy and often arise in the setting of abnormal surrounding mucosa, particularly Helicobacter pylori, autoimmune gastritis, and reactive gastropathy. Not infrequently gastroenterologists fail to biopsy the surrounding mucosa, thus determining the underlying etiology of the gastric hyperplastic polyp can be difficult. Recently, the Rodger C. Haggitt Gastrointestinal Pathology Society published guidelines on the use of special stains. The society guidelines indicate that H pylori are not usually present in hyperplastic polyps and special stains in this setting may have limited utility. We analyzed the histologic features of 32 gastric hyperplastic polyps in which the nonpolypoid mucosa demonstrated H pylori gastritis. A consecutive series of 50 hyperplastic polyps in which no surrounding mucosa was sampled was also analyzed. When H pylori are identified in biopsies of the nonpolypoid mucosa, it is also commonly present within the polyp tissue (22/32, 69%). The majority of H pylori organisms were identified on routine hematoxylin and eosin stain (16/22, 72%). In contrast, H pylori were only seen in 2/50 consecutive hyperplastic polyps in which the surrounding mucosa was not sampled. Compared with the hyperplastic polyps that lack the organisms, H pylori associated hyperplastic polyps more commonly had dense lymphoplasmacytic inflammation (P = .0001) and neutrophils within gastric epithelium (P = .036). Polyp location, number, size, and presence of intestinal metaplasia was not associated with H pylori These results provide empirical data to guide evaluation of hyperplastic polyps for H pylori.

The gut microbiota in conventional and serrated precursors of colorectal cancer.

BACKGROUND: Colorectal cancer is a heterogeneous disease arising from at least two precursors-the conventional adenoma (CA) and the serrated polyp. We and others have previously shown a relationship between the human gut microbiota and colorectal cancer; however, its relationship to the different early precursors of colorectal cancer is understudied. We tested, for the first time, the relationship of the gut microbiota to specific colorectal polyp types. RESULTS: Gut microbiota were assessed in 540 colonoscopy-screened adults by 16S rRNA gene sequencing of stool samples. Participants were categorized as CA cases (n = 144), serrated polyp cases (n = 73), or polyp-free controls (n = 323). CA cases were further classified as proximal (n = 87) or distal (n = 55) and as non-advanced (n = 121) or advanced (n = 22). Serrated polyp cases were further classified as hyperplastic polyp (HP; n = 40) or sessile serrated adenoma (SSA; n = 33). We compared gut microbiota diversity, overall composition, and normalized taxon abundance among these groups. CA cases had lower species richness in stool than controls (p = 0.03); in particular, this association was strongest for advanced CA cases (p = 0.004). In relation to overall microbiota composition, only distal or advanced CA cases differed significantly from controls (p = 0.02 and p = 0.002). In taxon-based analysis, stool of CA cases was depleted in a network of Clostridia operational taxonomic units from families Ruminococcaceae, Clostridiaceae, and Lachnospiraceae, and enriched in the classes Bacilli and Gammaproteobacteria, order Enterobacteriales, and genera Actinomyces and Streptococcus (all q < 0.10). SSA and HP cases did not differ in diversity or composition from controls, though sample size for these groups was small. Few taxa were differentially abundant between HP cases or SSA cases and controls; among them, class Erysipelotrichi was depleted in SSA cases. CONCLUSIONS: Our results indicate that gut microbes may play a role in the early stages of colorectal carcinogenesis through the development of CAs. Findings may have implications for developing colorectal cancer prevention therapies targeting early microbial drivers of colorectal carcinogenesis.

Epitheliocystis in lake trout Salvelinus namaycush (Walbaum) is associated with a ß-proteobacteria.

Lake trout Salvelinus namaycush (Walbaum) raised for stocking experienced yearly (2011-13) winter epizootics of epitheliocystis. Affected fish were dispersed on the bottom of the tank, had decreased feed and fright response, and mortality often reached 40%. Peak mortality occurred within 3 weeks of the appearance of clinical signs, and outbreaks typically lasted 6 weeks. Affected fish had no gross lesions but histologically had branchial epithelial necrosis and lamellar hyperplasia, with small to large numbers of scattered epithelial cells containing 10- to 20-µm inclusions. A longitudinal study was undertaken of one annual outbreak, and lamellar hyperplasia was most closely associated with mortality. The number of inclusions was statistically greater (P < 0.05) before and during peak mortality, but inclusions were present in low numbers before clinical signs occurred. Results of histochemical staining, immunohistochemistry and transmission electron microscopy supported the presence of a ß-proteobacteria rather than a Chlamydiales bacterium within inclusions. PCR primers to identify Chlamydiales did not give consistent results. However, the use of universal 16S rDNA bacterial primers in conjunction with laser capture microdissection of inclusions demonstrated that a ß-proteobacteria was consistently associated with affected gills and is more likely the cause of the disease in lake trout.

Citrobacter rodentium-induced colitis: A robust model to study mucosal immune responses in the gut.

Citrobacter rodentium is a natural mouse pathogen which reproducibly infects mice and causes intestinal disease. The C. rodentium model of infection is very useful for investigating host-pathogen immune interactions in the gut, and can also be used to understand the pathogenesis of several important human intestinal disorders, including Crohn's disease, ulcerative colitis, dysbiosis and colon tumorigenesis. Both innate and adaptive immune responses play a critical role in protection against C. rodentium. Here, we summarize the role of immune components in protection against C. rodentium and describe techniques for the analysis of innate and adaptive mucosal immune responses, including setting up the infection, analysis of colonic hyperplasia and bacterial dissemination, evaluation of antibody responses, and purification and analysis of intestinal epithelial and lymphoid cells.

An association between Helicobacter pylori and upper respiratory tract disease: fact or fiction?

Helicobacter pylori (H. pylori) is a major cause of chronic gastritis and gastric ulcers and considerable evidence supports the notion that infection with this bacterium is also associated with gastric malignancy in addition to various other conditions including pulmonary, vascular and autoimmune disorders. Gastric juice infected with H. pylori might play an important role in upper respiratory tract infection. Although direct and/or indirect mechanisms might be involved in the association between H. pylori and upper respiratory tract diseases, the etiological role of H. pylori in upper respiratory tract disorders has not yet been fully elucidated. Although various studies over the past two decades have suggested a relationship between H. pylori and upper respiratory tract diseases, the findings are inconsistent. The present overview describes the outcomes of recent investigations into the impact of H. pylori on upper respiratory tract and adjacent lesions.