Duodenal Metatranscriptomics to Define Human and Microbial Functional Alterations Associated with Severe Obesity: A Pilot Study.

Ilaria Granata,Carmela Nardelli,Vincenzo Pilone,Valeria D’Argenio,Lucia Sacchetti,Mario Rosario Guarracino,Gerardo Nardone,Debora Compare,Salvatore Tramontano

doi:10.3390/microorganisms8111811

Abstract

Obesity is a multifactorial disorder, and the gut microbiome has been suggested to contribute to its onset. In order to better clarify the role of the microbiome in obesity, we evaluated the metatranscriptome in duodenal biopsies from a cohort of 23 adult severely obese and lean control subjects using next generation sequencing. Our aim was to provide a general picture of the duodenal metatranscriptome associated with severe obesity. We found altered expressions of human and microbial genes in the obese compared to lean subjects, with most of the gene alterations being present in the carbohydrate, protein, and lipid metabolic pathways. Defects were also present in several human genes involved in epithelial intestinal cells differentiation and function, as well as in the immunity/inflammation pathways. Moreover, the microbial taxa abundance inferred by our transcriptomic data differed in part from the data that we previously evaluated by 16S rRNA in 13/23 individuals of our cohort, particularly concerning the Firmicutes and Proteobacteria phyla abundances. In conclusion, our pilot study provides the first taxonomic and functional characterization of duodenal microbiota in severely obese subjects and lean controls. Our findings suggest that duodenal microbiome and human genes both play a role in deregulating metabolic pathways, likely affecting energy metabolism and thus contributing to the obese phenotype.

Highlights

Obesity is a pandemic disease whose prevalence has dramatically increased since the 1970s
Urea (p-value ≤ 0.001), glucose (p-value ≤ 0.001), and total cholesterol (p-value ≤ 0.05) levels were significantly higher in blood from obese subjects than in controls, whereas albumin levels were significantly lower in obese subjects (p-value ≤ 0.05)
We describe the metatranscriptomics profile associated with obesity, which includes transcripts, the contributing bacterial organisms, and the specialized pathways differentially expressed between the two groups of participants; a comparison between bacterial composition and transcriptome-related data of the human duodenal microbiome; and, the putative convergence on key metabolic pathways between host and microbial transcripts, which might be associated with the obesity-associated phenotype

Summary

Introduction

Obesity is a pandemic disease whose prevalence has dramatically increased since the 1970s. The number of severely obese individuals (body mass index (BMI) ≥ 40 kg/m2) has increased faster than that of obese subjects (BMI ≥ 30 kg/m2) [1]. Obesity is a risk factor for metabolic disorders, autoimmune diseases, and cancer [2,3,4], and dramatically impacts healthcare costs [5]. Severely obese subjects have a much greater risk for diabetes and other diseases than mildly obese subjects and are predicted to increase healthcare costs in the future [6]. A better understanding of the pathogenic factors involved in the onset and progression of obesity may lead to interventions to reduce its spread and contain the related costs. Except for monogenic forms of obesity accounting for only 5% of severe obesity cases [7], obesity is driven by genetics, epigenetics, lifestyle, and the environment, each of which impacts the energy balance [8,9,10,11]

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