Abstract
Cross-sectional studies conducted with obese and control subjects have suggested associations between gut microbiota alterations and obesity, but the links with specific disease phenotypes and proofs of causality are still scarce. The present study aimed to profile the gut microbiota of lean and obese children with and without insulin resistance to characterize associations with specific obesity-related complications and understand the role played in metabolic inflammation. Through massive sequencing of 16S rRNA gene amplicons and data analysis using a novel permutation approach, we have detected decreased incidence of Blautia species, especially Blautia luti and B. wexlerae, in the gut microbiota of obese children, which was even more pronounced in cases with both obesity and insulin resistance. There was also a parallel increase in proinflammatory cytokines and chemokines (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], and monocyte chemoattractant protein 1 [MCP-1]) in feces of obese children compared to those of lean ones. B. luti and B. wexlerae were also shown to exert an anti-inflammatory effect in peripheral blood mononuclear cell cultures in vitro, compared to non-obesity-associated species. We suggest that the depletion of B. luti and B. wexlerae species in the gut ecosystem may occur in cases of obesity and contribute to metabolic inflammation leading to insulin resistance.IMPORTANCE Child obesity constitutes a risk factor for developing insulin resistance which, if sustained, could lead to more severe conditions like type 2 diabetes (T2D) in adulthood. Our study identified previously unknown species whose depletion (Blautia luti and Blautia wexlerae) is associated with insulin resistance in obese individuals. Our results also indicate that these bacterial species might help to reduce inflammation causally linked to obesity-related complications. Childhood is considered a window of opportunity to tackle obesity. These new findings provide, therefore, valuable information for the future design of microbiota-based strategies for the early prevention of obesity-related complications.
Highlights
IMPORTANCE Child obesity constitutes a risk factor for developing insulin resistance which, if sustained, could lead to more severe conditions like type 2 diabetes (T2D) in adulthood
The obese children showed a higher body mass index (BMI) z-score according to the study group classification
AValues are expressed in nanograms of cytokine per gram of stool and as the medians of respective distributions accompanied by Q1 and Q3 boundaries within parentheses. bP values resulting from pairwise comparison between groups using Wilcoxon rank sum test
Summary
IMPORTANCE Child obesity constitutes a risk factor for developing insulin resistance which, if sustained, could lead to more severe conditions like type 2 diabetes (T2D) in adulthood. Our study identified previously unknown species whose depletion (Blautia luti and Blautia wexlerae) is associated with insulin resistance in obese individuals. Childhood is considered a window of opportunity to tackle obesity. These new findings provide, valuable information for the future design of microbiota-based strategies for the early prevention of obesity-related complications. Childhood obesity is of special concern, as the number of overweight children and adolescents has increased 10-fold in the last 40 years [4]. Of these individuals, over 60% are expected to remain overweigh in early. The set of microorganisms involved in weight gain and adiposity has yet to be identified in detail, studies show that the obese phenotype can be transmitted to lean individuals by transferring to them the gut microbiota of obese individuals and, that the obesogenic features of the microbiota are modulated by diet [12]
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