Intestinal Permeability Is Associated With Visceral Adiposity in Healthy Women

Abstract

Increased visceral fat, as opposed to subcutaneous/gluteal, most strongly relates to key metabolic dysfunctions including insulin resistance, hepatic steatosis, and inflammation. Mesenteric fat hypertrophy in patients with Crohn's disease and in experimental rodent models of gut inflammation suggest that impaired gut barrier function with increased leakage of gut‐derived antigens may drive visceral lipid deposition. The aim of this study was to determine whether increased intestinal permeability is associated with visceral adiposity in healthy humans. Normal to overweight female subjects were recruited from a population‐based cohort. Intestinal permeability was assessed using the ratio of urinary excretion of orally ingested sucralose to mannitol (S/M). In study 1 (n = 67), we found a positive correlation between waist circumference and S/M excretion within a time frame of urine collection consistent with permeability of the lower gastrointestinal tract (6–9 hours post‐ingestion; P = 0.022). These results were followed up in study 2 (n = 55) in which we used computed tomography and dual energy X‐ray absorptiometry to measure visceral and subcutaneous fat areas of the abdomen, liver fat content, and total body fat of the same women. The S/M ratio from the 6–12 h urine sample correlated with visceral fat area (P = 0.0003) and liver fat content (P = 0.004), but not with subcutaneous or total body fat. This novel finding of an association between intestinal permeability and visceral adiposity and liver fat content in healthy humans suggests that impaired gut barrier function should be further explored as a possible mediator of excess visceral fat accumulation and metabolic dysfunction.

Fecal transplant: A safe and sustainable clinical therapy for restoring intestinal microbial balance in human disease?

“…Based on these findings, we have recently initiated a randomized controlled double blinded trial using fecal transplantation to investigate the effect on beta cell insulin secretion capacity in subjects with recently diagnosed type 1 diabetes mellitus. This work is in line with our previous work in insulin resistant (type 2 diabetes mellitus) subjects who are also characterized by increased intestinal permeability [29] and altered intestinal microbiota composition [30]. In a double blind randomized controlled trial in 18 treatment-naive insulin resistant male subjects, we were the first to show that fecal transplantation induced changes in specific (small) intestinal butyrate producing bacteria were associated with (temporarily) improved insulin sensitivity [31].…”

Functional interactions between the gut microbiota and host metabolism

“…Permeability is correlated with increased visceral adiposity and hepatic steatosis 72 , and those with high visceral adiposity and type 2 diabetes have increased levels of bacterial DNA in their blood 73 . However, inflammation may increase permeability in the gut, and further investigation into whether increased permeability causes adipose inflammation or increased inflammation contributes to increased permeability is needed.…”

Dietary lipid emulsions and endotoxemia

“…In humans, recent studies showed that plasma endotoxemia was higher in obese subjects with type 2 diabetes (Creely et al, 2007) and in patients suffering from inflammatory gut diseases (Pastor Rojo et al, 2007) compared with healthy controls. Increased intestinal permeability is also associated with visceral adiposity in otherwise healthy women (normal-weight and overweight) (Gummesson et al, 2011). Moreover, increased plasma endotoxemia was associated with higher food intake and correlated notably with higher fat intake in healthy subjects with metabolic and cardiovascular risk factors (Amar et al, 2008).…”