Abstract

Recent findings suggest an association between obesity, loss of gut barrier function and changes in microbiota profiles. Our primary objective was to examine the effect of caloric restriction and subsequent weight reduction on gut permeability in obese women. The impact on inflammatory markers and fecal microbiota was also investigated. The 4-week very-low calorie diet (VLCD, 800 kcal/day) induced a mean weight loss of 6.9 ± 1.9 kg accompanied by a reduction in HOMA-IR (Homeostasis model assessment-insulin resistance), fasting plasma glucose and insulin, plasma leptin, and leptin gene expression in subcutaneous adipose tissue. Plasma high-molecular weight adiponectin (HMW adiponectin) was significantly increased after VLCD. Plasma levels of high-sensitivity C-reactive protein (hsCRP) and lipopolysaccharide-binding protein (LBP) were significantly decreased after 28 days of VLCD. Using three different methods, gut paracellular permeability was decreased after VLCD. These changes in clinical parameters were not associated with major consistent changes in dominant bacterial communities in feces. In summary, a 4-week caloric restriction resulted in significant weight loss, improved gut barrier integrity and reduced systemic inflammation in obese women.

Highlights

  • A chronic positive energy balance leads to obesity and low-grade inflammation

  • Based on the observation that obesity is associated with a chronic low-grade inflammatory state and, potentially, impaired gut permeability[7], the present study aimed to investigate whether caloric restriction is able to modulate gut permeability and, thereby, decrease markers of inflammation in human subjects

  • The VLCD resulted in a significant decrease in body weight and fat mass as well as improvement of fasting blood glucose, insulin, HOMA-IR and lipid parameters

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Summary

Introduction

A chronic positive energy balance leads to obesity and low-grade inflammation. This subclinical inflammatory state is considered to pave the way for insulin resistance and subsequent type 2 diabetes mellitus[1,2] and to promote cardiovascular diseases[3]. The reasons for this low-grade inflammation are poorly understood. It may, in part, be explained by macrophage infiltration into adipose tissue[4,5]. Recent studies suggested that increased gut permeability[7] and lipopolysaccharides (LPS) translocation may play an important role[8,9]. Weight reduction is known to improve metabolic disturbances and to decrease the systemic inflammatory tone[21,22]

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