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1.
Metabolites ; 13(7)2023 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-37512526

RESUMO

Microbiota and the metabolites they produce within the large intestine interact with the host epithelia under the influence of a range of host-derived metabolic, immune, and homeostatic factors. This complex host-microbe interaction affects intestinal tumorigenesis, but established microbial or metabolite profiles predicting colorectal cancer (CRC) risk are missing. Here, we aimed to identify fecal bacteria, volatile organic compounds (VOC), and their associations that distinguish healthy (non-adenoma, NA) from CRC prone (high-risk adenoma, HRA) individuals. Analyzing fecal samples obtained from 117 participants ≥15 days past routine colonoscopy, we highlight the higher abundance of Proteobacteria and Parabacteroides distasonis, and the lower abundance of Lachnospiraceae species, Roseburia faecis, Blautia luti, Fusicatenibacter saccharivorans, Eubacterium rectale, and Phascolarctobacterium faecium in the samples of HRA individuals. Volatolomic analysis of samples from 28 participants revealed a higher concentration of five compounds in the feces of HRA individuals, isobutyric acid, methyl butyrate, methyl propionate, 2-hexanone, and 2-pentanone. We used binomial logistic regression modeling, revealing 68 and 96 fecal bacteria-VOC associations at the family and genus level, respectively, that distinguish NA from HRA endpoints. For example, isobutyric acid associations with Lachnospiraceae incertae sedis and Bacteroides genera exhibit positive and negative regression lines for NA and HRA endpoints, respectively. However, the same chemical associates with Coprococcus and Colinsella genera exhibit the reverse regression line trends. Thus, fecal microbiota and VOC profiles and their associations in NA versus HRA individuals indicate the significance of multiple levels of analysis towards the identification of testable CRC risk biomarkers.

2.
Metabolites ; 12(6)2022 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-35736432

RESUMO

Colorectal cancer (CRC) is one of the most prevalent cancers affecting humans, with a complex genetic and environmental aetiology. Unlike cancers with known environmental, heritable, or sex-linked causes, sporadic CRC is hard to foresee and has no molecular biomarkers of risk in clinical use. One in twenty CRC cases presents with an established heritable component. The remaining cases are sporadic and associated with partially obscure genetic, epigenetic, regenerative, microbiological, dietary, and lifestyle factors. To tackle this complexity, we should improve the practice of colonoscopy, which is recommended uniformly beyond a certain age, to include an assessment of biomarkers indicative of individual CRC risk. Ideally, such biomarkers will be causal to the disease and potentially modifiable upon dietary or therapeutic interventions. Multi-omics analysis, including transcriptional, epigenetic as well as metagenomic, and metabolomic profiles, are urgently required to provide data for risk analyses. The aim of this article is to provide a perspective on the multifactorial derailment of homeostasis leading to the initiation of CRC, which may be explored via multi-omics and Gut-on-Chip analysis to identify much-needed predictive biomarkers.

3.
Ann Gastroenterol ; 32(2): 208-210, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30872912

RESUMO

Mastocytosis is a rare and heterogeneous group of diseases whose common element is the presence of dense mast-cell infiltrates in various tissues. The gastrointestinal (GI) tract is frequently affected with vague and subtle manifestations, making the diagnosis of GI mastocytosis rather formidable and challenging. The diagnosis of the disease requires a high level of clinical suspicion and an index of familiarity. To our knowledge, this is the first case of indolent systemic mastocytosis with colonic ulcerations. Because of the unusual presentation of mastocytosis, it was initially misdiagnosed as Crohn's disease; the diagnosis of mastocytosis was established after further evaluation of the patient's history and further investigation. Systemic mastocytosis should therefore be considered in the differential diagnosis in patients presenting with abdominal manifestations that cannot be otherwise explained or attributed to common GI pathologies and in cases where the patient's trajectory does not follow the expected course. More research is needed into the epidemiology and the non-classical presentation of systemic mastocytosis in order to increase awareness of the disease in the medical community.

4.
J Infect Dev Ctries ; 7(9): 642-50, 2013 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-24042099

RESUMO

INTRODUCTION: The prevalence of H. pylori varies with geographic locations. To date there are no epidemiological data on its prevalence in Cyprus; therefore, we determined the prevalence and molecular characteristics of H. pylori infection in Cypriot patients. METHODOLOGY: DNA extracted from 103 gastric biopsies was analyzed for the presence of H. pylori by PCR using primers for ureA. H. pylori-positive biopsies were characterized by PCR using specific primers for cagA and vacA genes. The presence of clarithromycin-associated resistant mutations such as A2143G, A2142G, A2142C in 23S rRNA gene of H. pylori-positive patients was determined using a real-time PCR allelic discrimination assay. RESULTS: H. pylori was detected in 41 (39.8%) biopsies and, out of these, 17 (41.5%) tested positive for the cagA gene. The vacA alleles m1, m2, s1a, s1b, and s2 were detected in 7 (17.1%), 34 (82.9%), 12 (29.3%), 2 (4.9%), and 22 (53.7%) isolates, respectively. One (2.4%) biopsy was vacA s1a and s2-positive while one (2.4%) was positive for vacA s1a, s1b, and s2. Three (7.3%) biopsies were untypable for vacA s1, s1b, and s2. The majority (35; 85.4%) of strains were susceptible to clarithromycin while two (4.9%) had the A2143G mutation. Three (7.3%) had a mixture of an A2143G point mutant and susceptible strains while one (2.4%) had a mixture of an A2142G point mutant and susceptible strains. CONCLUSIONS: The distribution of the virulence factors cagA and vacA in the Cypriot strains resembled that of strains circulating in Middle Eastern countries geographically close to Cyprus.


Assuntos
Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Fatores de Virulência/genética , Adulto , Antibacterianos/farmacologia , Biópsia , Claritromicina/farmacologia , Chipre/epidemiologia , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Farmacorresistência Bacteriana , Mucosa Gástrica/microbiologia , Helicobacter pylori/isolamento & purificação , Humanos , Filogeografia , Mutação Puntual , Prevalência , RNA Ribossômico 23S/genética , Urease/genética
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