Evidence for metabolic endotoxemia in obese and diabetic Gambian women

Abstract

Objective:Emerging evidence from animal models suggests that translocation of bacterial debris across a leaky gut may trigger low-grade inflammation, which in turn drives insulin resistance. The current study set out to investigate this phenomenon, termed ‘metabolic endotoxemia', in Gambian women.Methods:In a cross-sectional study, we recruited 93 age-matched middle-aged urban Gambian women into three groups: lean (body mass index (BMI): 18.5–22.9 kg m−2), obese non-diabetic (BMI: ⩾30.0 kg m−2) and obese diabetic (BMI: ⩾30.0 kg m−2 and attending a diabetic clinic). We measured serum bacterial lipopolysaccharide (LPS) and endotoxin-core IgM and IgG antibodies (EndoCAb) as measures of endotoxin exposure and interleukin-6 (IL-6) as a marker of inflammation.Results:Inflammation (IL-6) was independently and positively associated with both obesity and diabetes (F=12.7, P<0.001). LPS levels were highest in the obese-diabetic group compared with the other two groups (F=4.4, P<0.02). IgM EndoCAb (but not total IgM) was highly significantly reduced in the obese (55% of lean value) and obese diabetic women (30% of lean; F=21.7, P<0.0001 for trend) compared with lean women.Conclusion:These data support the hypothesis that gut-derived inflammatory products are associated with obesity and diabetes. Confirmation of these findings and elucidation of the role of the microbiota, gut damage and the pathways for translocation of bacterial debris, could open new avenues for prevention and treatment of type 2 diabetes.

Effects of 1α,25 Dihydroxyvitamin D3 on Pro‐inflammatory Cytokines of Palmitic Acid Treated Thp‐1 Cells

“…Fat‐enriched diet can increase the level of lipopolysaccharide (LPS) in murine plasma, which could trigger chronic inflammation, obesity, and insulin resistance (Cani and others ). The same findings in humans were reported by Hawkesworth and others ().…”

Association of the gut microbiota with colorectal cancer in a South Asian cohort of patients

“…Therefore, bacteria of the Phylum Proteobacteria do appear to be 100-fold more abundant in South Asian patients with DM, similar to the observations in Western countries, despite differences in their diets [23]. This gut microbial dysbiosis that occurs due to the overgrowth of bacteria of the Phylum Proteobacteria has shown to associate with low grade endotoxaemia [24]. The presence of low levels of bacterial lipopolysaccharide (LPS) has shown to associate with DM and other metabolic diseases such as non-alcoholic steatohepatitis, which are rapidly increasing in all South Asian countries [25][26][27].…”

The gut microbiota and metabolic disease: current understanding and future perspectives

“…Further, it was demonstrated that this signalling requires the LPS receptor CD14 and that microbial activation of the innate immune signalling cascade in adipocytes promotes secretion of the chemokine CCL2 , which subsequently promotes accumulation of macrophages in adipose tissue. LPS levels increased in human subjects with type 2 diabetes and was associated with increased risk of developing diabetes . Administration of LPS in humans induced insulin resistance by triggering inflammatory reactions , whereas in mice it enhanced levels of hepatic pro‐inflammatory lipid mediators causing liver injury .…”