RESUMO
The impact of therapeutic interventions on the human gut microbiota (GM) is a clinical issue of paramount interest given the strong interconnection between microbial dynamics and human health. Orally administered antibiotics are known to reduce GM biomass and modify GM taxonomic profile. However, the impact of antimicrobial therapies on GM functions and biochemical pathways has scarcely been studied. Here, we characterized the fecal metaproteome of 10 Helicobacter pylori-infected patients before (T0) and after 10 days (T1) of a successful quadruple therapy (bismuth, tetracycline, metronidazole, and rabeprazole) and 30 days after therapy cessation (T2), to investigate how GM and host functions change during the eradication and healing processes. At T1, the abundance ratio between microbial and host proteins was reversed compared with that at T0 and T2. Several pathobionts (including Klebsiella, Proteus, Enterococcus, Muribaculum, and Enterocloster) were increased at T1. Therapy reshaped the relative contributions of the functions required to produce acetate, propionate, and butyrate. Proteins related to the uptake and processing of complex glycans were increased. Microbial cross-feeding with sialic acid, fucose, and rhamnose was enhanced, whereas hydrogen sulfide production was reduced. Finally, microbial proteins involved in antibiotic resistance and inflammation were more abundant after therapy. Moreover, a reduction in host proteins with known roles in inflammation and H. pylori-mediated carcinogenesis was observed. In conclusion, our results support the use of metaproteomics to monitor drug-induced remodeling of GM and host functions, opening the way for investigating new antimicrobial therapies aimed at preserving gut environmental homeostasis.
Assuntos
Microbioma Gastrointestinal , Infecções por Helicobacter , Helicobacter pylori , Humanos , Infecções por Helicobacter/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Tetraciclina/uso terapêutico , Bismuto/uso terapêutico , Inflamação , Amoxicilina/uso terapêuticoRESUMO
OBJECTIVES: To examine cancer trend using age-period-cohort analysis with a cohort of patients in Sardinia, Italy, where epidemiological transition occurred between 1950 and 1960. METHODS: Poisson log-linear regression models were used to analyze time trend in patients undergoing upper endoscopy between 1995 and 2013. RESULTS: A total of 10,546 clinical records (62.2% women) were retrieved. In 541 patients (5.1%), a diagnosis of cancer was reported, more often in men (5.5%) than in women (4.9%). Age and birth cohort were significantly associated with cancer rate according to age-period-cohort analysis (p < 0.0001), whereas the effect of time period was negligible (p = 0.875). An upward trend for all cancers was observed in the younger generations (7.15% before 1950, 8.85% between 1950 and 1960, and 10.7% after 1960). CONCLUSIONS: Population aging and increased exposure to cancer risk factors after epidemiological transition were the major determinants associated with cancer in this Sardinian cohort, whereas time period had no effect, ruling out any variation in diagnostic accuracy. These results may facilitate the provision of preventive measures by the health care system, and improve population-tailored cancer screening strategies.
Assuntos
Neoplasias/epidemiologia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Fatores Socioeconômicos , Fatores de Tempo , Adulto JovemRESUMO
Currently, standard endoscopy is not considered enough reliable for the evaluation of celiac disease, neither to drive biopsy sampling. The diagnostic reliability of the endoscopic assessment of celiac disease has been increased by the recent advancement of software and hardware technologies. Several endoscopic technologies have been investigated so far for the diagnostic evaluation of celiac disease, including: water-immersion techniques, dye-based and dye-less chromoendoscopy techniques (Narrow band imaging; Fujinon Intelligeng Chromo Endoscopy; I-scan); optical coherence tomography; confocal laser endomicroscopy; high-resolution magnification endoscopy; videocapsule endoscopy; enteroscopy. Such a technologic improvement brought us to higher diagnostic possibilities in the evaluation and management of CD. A wider application of advanced diagnostic endoscopic techniques is therefore warranted to decrease the number of misdiagnoses and related healthcare costs of celiac disease.
Assuntos
Doença Celíaca/patologia , Duodenoscopia/métodos , Duodeno/patologia , Processamento de Imagem Assistida por Computador/métodos , Software , Tomografia de Coerência Óptica/métodos , Feminino , Humanos , MasculinoRESUMO
The progressive loss of efficacy of standard eradication therapies has made the treatment of Helicobacter pylori (H. pylori) more challenging than ever. Endoscopic-guided antibiotic susceptibility testing had previously been suggested to guide treatment after failure of second-line therapies. However, its role has expanded over the years, in accordance with the current Maastricht Guidelines. Several authors have dealt with this topic, developing both efficacy trials and cost-effectiveness trials against resistant H. pylori infections as well as infections in naïve patients. However, results are not homogeneous enough to provide definite advice, because antibiotic resistance is not the only reason for treatment failure. Moreover, the culture-guided approach is surrounded by many practical issues, such as the availability of both endoscopy units and microbiology laboratories, and the need for a standard of quality that cannot be satisfied everywhere. Finally, pre-treatment susceptibility testing should be part - and not the only weapon - of a targeted, personalized strategy to overcome H. pylori infection.