Abstract

ObjectiveThe intestinal flora of gut microbiota in obese Chinese children and adolescents with and without insulin resistance (IR) was analyzed, as well as associations between the gut microbiota and two serum cytokines related to glucose metabolism, adropin and angiopoietin-like 4 (ANGPTL4).MethodsClinical data, fecal bacterial composition, glucose-related hormones, and serum adipokines (adropin and ANGPTL4) were analyzed in 65 Chinese children with exogenous obesity. The composition of the gut microbiota was determined by 16S rRNA-based metagenomics and IR was calculated using the homeostasis model assessment (HOMA).ResultsThe 65 obese subjects were divided into two groups: insulin sensitive (IS) (n=40, 57.5% males) or IR (n=25, 60% males). Principal coordinates analysis revealed that the gut microbiota samples from the IS group clustered together and separated partly from the IR group (p=0.008). By Mann-Whitney U-test, at a phylum level, a reduction of Firmicutes and an increase of Bacteroidetes in the IR subjects was observed. LEfSe analysis revealed that IS subject, when compared to their IR counterparts, harbored members of the order Coriobacteriales, Turicibacterales, Pasteurellales and family Turicibacteraceae, that were significantly more abundant. In contrast, the IR subjects had members of family Peptococcaceae that were significantly more prevalent than the IS subjects (all p<0.05). Spearman’s correlation analysis revealed that serum ANGPTL4 was positively associated with genus Bacteroides, Butyricimonas, and Alistipes, and adropin was positively associated with genus Anaerostipes and Alistipes, and negatively associated with genus Blautia (all p<0.05).ConclusionIn obese children, the gut microbiome in IR subjects was significantly discordant from the IS subjects, and the abundance of some metabolism-related bacteria correlated with the serum concentrations of adropin and ANGPTL4. These observations infer that the gut microbiota may be involved in the regulation of glucose metabolism in obesity.

Highlights

  • The worrisome prevalence of obesity among children, adolescents, and adults is arguably one of the most serious public health concerns worldwide given the proclivity for cardiovascular diseases and type 2 diabetes (T2DM) [1]

  • There were no differences in gender, dietary habits, BMI-Z, waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), Fasting plasma glucose (FPG), fasting INS, serum adropin and ANGPLT4 between the two cohorts

  • We identified an overall of 146 operational taxonomic units (OTUs), among which 136 OTU with ≥2 counts, and they were grouped in 10 phylum and 38 families

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Summary

Introduction

The worrisome prevalence of obesity among children, adolescents, and adults is arguably one of the most serious public health concerns worldwide given the proclivity for cardiovascular diseases and type 2 diabetes (T2DM) [1]. The major cause of IR in obesity is aberrant cellular lipid partitioning pattern characterized by increased deposition of lipids within insulin-responsive tissues, such as the liver and skeletal muscle. This divergent lipid accumulation is associated with infiltration of intraabdominal cells of the immune system, which induces a systemic, low-grade inflammation [2]. Gut microbiota dysbiosis has been proposed as an etiologic factor underlying metabolic disease associated with IR, such as obesity and T2DM [3,4,5,6]. Notwithstanding the recent scrutiny of the intestinal flora in numerous disorders, little is known about the characteristics of the gut microbiota in children, let alone those who are obese [15]

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