Comparison between 16S rRNA and shotgun sequencing in colorectal cancer, advanced colorectal lesions, and healthy human gut microbiota.

BACKGROUND: Gut dysbiosis has been associated with colorectal cancer (CRC), the third most prevalent cancer in the world. This study compares microbiota taxonomic and abundance results obtained by 16S rRNA gene sequencing (16S) and whole shotgun metagenomic sequencing to investigate their reliability for bacteria profiling. The experimental design included 156 human stool samples from healthy controls, advanced (high-risk) colorectal lesion patients (HRL), and CRC cases, with each sample sequenced using both 16S and shotgun methods. We thoroughly compared both sequencing technologies at the species, genus, and family annotation levels, the abundance differences in these taxa, sparsity, alpha and beta diversities, ability to train prediction models, and the similarity of the microbial signature derived from these models. RESULTS: As expected, the results showed that 16S detects only part of the gut microbiota community revealed by shotgun, although some genera were only profiled by 16S. The 16S abundance data was sparser and exhibited lower alpha diversity. In lower taxonomic ranks, shotgun and 16S highly differed, partially due to a disagreement in reference databases. When considering only shared taxa, the abundance was positively correlated between the two strategies. We also found a moderate correlation between the shotgun and 16S alpha-diversity measures, as well as their PCoAs. Regarding the machine learning models, only some of the shotgun models showed some degree of predictive power in an independent test set, but we could not demonstrate a clear superiority of one technology over the other. Microbial signatures from both sequencing techniques revealed taxa previously associated with CRC development, e.g., Parvimonas micra. CONCLUSIONS: Shotgun and 16S sequencing provide two different lenses to examine microbial communities. While we have demonstrated that they can unravel common patterns (including microbial signatures), shotgun often gives a more detailed snapshot than 16S, both in depth and breadth. Instead, 16S will tend to show only part of the picture, giving greater weight to dominant bacteria in a sample. Therefore, we recommend choosing one or another sequencing technique before launching a study. Specifically, shotgun sequencing is preferred for stool microbiome samples and in-depth analyses, while 16S is more suitable for tissue samples and studies with targeted aims.

Performance of a Shotgun Prediction Model for Colorectal Cancer When Using 16S rRNA Sequencing Data.

Colorectal cancer (CRC), the third most common cancer globally, has shown links to disturbed gut microbiota. While significant efforts have been made to establish a microbial signature indicative of CRC using shotgun metagenomic sequencing, the challenge lies in validating this signature with 16S ribosomal RNA (16S) gene sequencing. The primary obstacle is reconciling the differing outputs of these two methodologies, which often lead to divergent statistical models and conclusions. In this study, we introduce an algorithm designed to bridge this gap by mapping shotgun-derived taxa to their 16S counterparts. This mapping enables us to assess the predictive performance of a shotgun-based microbiome signature using 16S data. Our results demonstrate a reduction in performance when applying the 16S-mapped taxa in the shotgun prediction model, though it retains statistical significance. This suggests that while an exact match between shotgun and 16S data may not yet be feasible, our approach provides a viable method for comparative analysis and validation in the context of CRC-associated microbiome research.

EPAGE no es una estrategia eficaz para la gestión de colonoscopias durante la pandemia por COVID-19 / The EPAGE guidelines are not an effective strategy for managing colonoscopies during the COVID-19 pandemic

Introducción: La pandemia producida por el virus SARS-CoV-2 ha generado un grave impacto en el funcionamiento de las unidades de endoscopia digestiva. La Asociación Española de Gastroenterología y la Sociedad Española de Endoscopia Digestiva (AEG-SEED) han propuesto la utilización de la guía European Panel on the Appropriateness of Gastrointestinal Endoscopy II (EPAGE) para la gestión de las colonoscopias pospuestas.Objetivo: Evaluar la guía EPAGE como herramienta de gestión en comparación con el test de sangre oculta en heces inmunológico (TSOHi) y con una calculadora de riesgo (CR), que incluye la edad, el sexo y el TSOHi, para la detección de cáncer colorrectal (CCR) y lesión significativa colónica (LSC).Métodos: Estudio unicéntrico prospectivo. Se incluyeron 743 pacientes derivados para una colonoscopia diagnóstica. Se clasificó cada solicitud según EPAGE en apropiada, indeterminada e inapropiada. Se les entregó un TSOHi y se calculó el valor de la CR.ResultadosEl TSOHi (p<0,001), pero no EPAGE (p = 0,742), fue una variable independiente de riesgo de CCR. El área bajo la curva receiver operating characteristic (ROC) de EPAGE, TSOHi y CR fue: 0,61(IC 95% 0,49 a 0,75), 0,95 (0,93 a 0,97) y 0,90 (0,87 a 0,93) para CCR; y 0,55 (0,49 a 0,61), 0,75 (0,69 a 0,813) y 0,78 (0,73 a 0,83) para LSC, respectivamente. El número necesario de colonoscopias para detectar un CCR y una LSC fue de 38 y siete para EPAGE, de siete y dos para TSOHi, y de 19 y cuatro para CR ≥ cinco puntos, respectivamente.Conclusión: La EPAGE, a diferencia del TSOHi, no es adecuada para seleccionar a los pacientes candidatos a colonoscopia diagnóstica para la detección de CCR. El TSOHi, en combinación con la edad y el sexo, es la estrategia correcta para gestionar la demanda de endoscopia en un escenario de acceso restrictivo.

Introduction: The pandemic caused by the SARS-CoV-2 virus has had a serious impact on the functioning of gastrointestinal endoscopy Units. The Asociación Española de Gastroenterología (AEG) and the Sociedad Española de Endoscopia Digestiva (SEED) have proposed the EPAGE guidelines for managing postponed colonoscopies.ObjectiveTo evaluate the EPAGE guidelines as a management tool compared to the immunologic faecal occult blood test (iFOBT) and compared to risk score (RS) that combines age, sex and the iFOBT for the detection of colorectal cancer (CRC) and significant bowel disease (SBD).Methods: A prospective, single-centre study enrolling 743 symptomatic patients referred for a diagnostic colonoscopy. Each order was classified according to the EPAGE guidelines as appropriate, indeterminate or inappropriate. Patients underwent an iFOBT and had their RS calculated.Results: The iFOBT (p<0.001), but not the EPAGE guidelines (p = 0.742), was an independent predictive factor of risk of CRC. The ROC AUCs for the EPAGE guidelines, the iFOBT and the RS were 0.61 (95% CI 0.49-0.75), 0.95 (0.93-0.97) and 0.90 (0.87-0.93) for CRC, and 0.55 (0.49-0.61), 0.75 (0.69-0.813) and 0.78 (0.73-0.83) for SBD, respectively. The numbers of colonoscopies needed to detect a case of CRC and a case of SBD were 38 and seven for the EPAGE guidelines, seven and two for the iFOBT, and 19 and four for a RS ≥5 points, respectively.Conclusion: The EPAGE guidelines, unlike the iFOBT, is not suitable for screening candidate patients for a diagnostic colonoscopy to detect CRC. The iFOBT, in combination with age and sex, is the most suitable strategy for managing demand for endoscopy in a restricted-access situation

Spontaneous intramural esophageal dissection: an unusual onset of eosinophilic esophagitis

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Contribution of infliximab population pharmacokinetic model for dose ptimization in ulcerative colitis patients

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Individualización de la terapia con infliximab: monitorización farmacocinética / Individualized infliximab therapy: pharmacokinetic monitoring

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Aproximación al diagnóstico y tratamiento de la anemia crónica secundaria a causas digestivas / Approach to the diagnosis and treatment of chronic anemia secondary to gastrointestinal diseases

La anemia ferropénica es la forma más frecuente de anemia. Puede causar astenia, deterioro cognitivo y funcional y descompensar las enfermedades de base. No es una enfermedad, sino la consecuencia de un problema médico potencialmente grave, por lo que siempre debe investigarse la causa subyacente; en varones y mujeres posmenopáusicas es la pérdida digestiva y la malabsorción de hierro. En este grupo se aconseja una gastroscopia, una colonoscopia y una serología de celiaquía. Si los resultados son negativos deberá valorarse la repetición de exploraciones y se acepta una pauta de tratamiento con hierro. En caso de refractariedad o recidiva de la anemia debe ser investigado el intestino delgado. En este caso la cápsula endoscópica es la exploración de elección. En todos los casos debe tratarse la anemia ferropénica hasta la normalización de los depósitos, para lo cual disponemos de una gran variedad de formas de hierro oral y parenteral

Iron deficiency anemia is the most common type of anemia and can cause asthenia, cognitive and functional impairment, and decompensation of underlying diseases. Iron deficiency anemia is not a disease but is the result of a potentially serious medical problem. Consequently, patients should always undergo investigation of the underlying cause. In men and postmenopausal women, the condition is caused by gastrointestinal loss and malabsorption of iron. In this group, recommended procedures are gastroscopy, colonoscopy and serological testing for celiac disease. If the results of these tests are negative, repeat examinations and iron therapy should be considered. In treatment-refractory or recurrent anemia, the small intestine should be investigated. In this case, the procedure of choice is capsule endoscopy. Iron deficiency anemia should always be treated until iron deposits have returned to normal levels. A wide variety of preparations are available, in both oral and parental formulations

Síndrome de poliposis serrada / Serrated polyposis syndrome

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Calprotectina fecal en el diagnóstico de enfermedades inflamatorias / Fecal calprotectin in the diagnosis of inflammatory bowel diseases

El diagnóstico de las enfermedades inflamatorias intestinales se ha basado, clásicamente, en la valoración de síntomas digestivos. Su aparición suele resultar en una colonoscopia, cuyo rendimiento es bajo. Asimismo, existe una tendencia creciente en fundamentar el tratamiento de la enfermedad inflamatoria intestinal en datos objetivos, ya que la desaparición de los signos de actividad en la colonoscopia (denominada «curación mucosa») se ha relacionado con una remisión clínica sostenida y una reducción en la tasa de hospitalización y cirugía. En consecuencia, es necesario identificar biomarcadores que permitan seleccionar aquellos pacientes que van a beneficiarse más de una exploración endoscópica. La calprotectina fecal ha sido propuesta como biomarcador de inflamación intestinal. Permite diferenciar la enfermedad inflamatoria intestinal del síndrome de intestino irritable, presenta una mejor correlación con el grado de inflamación que los índices clínicos y marcadores serológicos. Además, podría ser útil para predecir la curación mucosa y el riesgo de recidiva (AU)

The diagnosis of inflammatory bowel diseases has classically been based on assessment of digestive symptoms. The development of these symptoms usually results in colonoscopy, which has a low diagnostic yield. Likewise, there is an increasing tendency to base treatment of inflammatory bowel disease on objective data, since the disappearance of signs of activity on colonoscopy (called «mucosal cure») has been associated with sustained clinical remission and reduced rates of hospitalization and surgery. Consequently, there is a need for biomarkers that would aid the selection of those patients who would derive most benefit from an endoscopic examination. One substance that has been proposed as a biomarker of bowel inflammation is fecal calprotectin. This substance allows inflammatory bowel disease to be distinguished from irritable bowel syndrome and shows a better correlation with the degree of inflammation than clinical indicators and serological markers. In addition, it could also be useful to predict mucosal cure and the risk of recurrence (AU)