Neuronal programming by microbiota regulates intestinal physiology.

Neural control of the function of visceral organs is essential for homeostasis and health. Intestinal peristalsis is critical for digestive physiology and host defence, and is often dysregulated in gastrointestinal disorders1. Luminal factors, such as diet and microbiota, regulate neurogenic programs of gut motility2-5, but the underlying molecular mechanisms remain unclear. Here we show that the transcription factor aryl hydrocarbon receptor (AHR) functions as a biosensor in intestinal neural circuits, linking their functional output to the microbial environment of the gut lumen. Using nuclear RNA sequencing of mouse enteric neurons that represent distinct intestinal segments and microbiota states, we demonstrate that the intrinsic neural networks of the colon exhibit unique transcriptional profiles that are controlled by the combined effects of host genetic programs and microbial colonization. Microbiota-induced expression of AHR in neurons of the distal gastrointestinal tract enables these neurons to respond to the luminal environment and to induce expression of neuron-specific effector mechanisms. Neuron-specific deletion of Ahr, or constitutive overexpression of its negative feedback regulator CYP1A1, results in reduced peristaltic activity of the colon, similar to that observed in microbiota-depleted mice. Finally, expression of Ahr in the enteric neurons of mice treated with antibiotics partially restores intestinal motility. Together, our experiments identify AHR signalling in enteric neurons as a regulatory node that integrates the luminal environment with the physiological output of intestinal neural circuits to maintain gut homeostasis and health.

Molecular profiling of enteric nervous system cell lineages.

The enteric nervous system (ENS) is an extensive network of enteric neurons and glial cells that is intrinsic to the gut wall and regulates almost all aspects of intestinal physiology. While considerable advancement has been made in understanding the genetic programs regulating ENS development, there is limited understanding of the molecular pathways that control ENS function in adult stages. One of the limitations in advancing the molecular characterization of the adult ENS relates to technical difficulties in purifying healthy neurons and glia from adult intestinal tissues. To overcome this, we developed novel methods for performing transcriptomic analysis of enteric neurons and glia, which are based on the isolation of fluorescently labeled nuclei. Here we provide a step-by-step protocol for the labeling of adult mouse enteric neuronal nuclei using adeno-associated-virus-mediated gene transfer, isolation of the labeled nuclei by fluorimetric analysis, RNA purification and nuclear RNA sequencing. This protocol has also been adapted for the isolation of enteric neuron and glia nuclei from myenteric plexus preparations from adult zebrafish intestine. Finally, we describe a method for visualization and quantification of RNA in myenteric ganglia: Spatial Integration of Granular Nuclear Signals (SIGNS). By following this protocol, it takes ~3 d to generate RNA and create cDNA libraries for nuclear RNA sequencing and 4 d to carry out high-resolution RNA expression analysis on ENS tissues.

Omission of breakfast and risk of gastric cancer in Mexico.

AIM: To investigate factors associated with gastric cancer (GC) in the Mexican population using a validated questionnaire. METHODS: We designed and validated in Spanish a Questionnaire to Find Factors Associated with Diseases of the Digestive Tract using GC as a model. A cross-sectional study using 49 subjects, with confirmed histopathological GC diagnosis, and 162 individuals without GC participated. Odds ratio and 95% CIs were estimated in univariate and multivariate analysis adjusted for possible confounding factors. In order to match age groups, a multivariate sub-analysis was performed in subjects ≥ 39 years of age and in females and males separately. RESULTS: In the univariate analysis, we found an association between GC and education to primary level or below, low socioeconomic status, the use of dental prostheses, omission of breakfast, consumption of very hot food and drink, addition of salt to prepared foods, consumption of salt-preserved foods and the pattern of alcohol consumption. We found protection against GC associated with the use of mouthwash, food refrigeration and regular consumption of fruit and vegetables. In the multivariate sub-analysis with subjects of ≥ 39 years, the omission of breakfast was identified as a risk factor for GC. CONCLUSION: Our study suggests an association between the omission of breakfast and the failure to refrigerate food with GC in the Mexican population.

Prevalencia de hipertensión arterial y nefropatía en pacientes con diabetes mellitus no insulinodependientes / Prevalence of arterial hypertension and nephropathy in patients with non-insulindependent diabetes mellitus

La prevalencia de hipertensión arterial en la población de pacientes diabéticos estudiada fue de 53,6 por ciento , superior a la encontrada en otros estudios, sin diferencias de sexo. La edad promedio de diagnóstico de hipertensión arterial en esta población es de 57 años, siendo, en promedio 6 años posterior al diagnóstico de la DMNID. La frecuencia de hipertensión arterial se mantiene constante en 50 por ciento hasta los 20 años de evolución de la DMNID con un aumento posterior a mayor de edad. La prevalencia de hipertensión arterial aumenta cuando hay mal control metabólico ee IMC más altos. Las prevalencia de nefropatía en lapoblación de pacientes diabéticos fue de 14,4 por ciento . No se encontró asociación entre control metabólico y nefropatía, ni entre esta última e hipertensión arterial