Abstract
Emerging evidence suggests a role for the gut microbiota in glucose metabolism and diabetes. Few studies have examined the associations between the faecal microbiome and insulin sensitivity and secretion using gold-standard methods in high-risk populations prior to diabetes onset. We investigated the relationships between faecal microbiota composition (16S rRNA sequencing) and gold-standard measures of insulin sensitivity (hyperinsulinaemic-euglycaemic clamp) and insulin secretion (intravenous glucose tolerance test) in 38 overweight or obese otherwise healthy individuals. Genus Clostridium was positively associated with insulin sensitivity, and genera Dialister and Phascolarctobacterium were related to both insulin sensitivity and secretion. Insulin sensitivity was associated with a higher abundance of Phascolarctobacterium and lower abundance of Dialister. Those with higher insulin secretion had a higher abundance of Dialister and lower abundance of Bifidobacterium, compared to those with lower insulin secretion. Body mass index (BMI) was positively correlated with Streptococcus abundance whereas Coprococcus abundance was negatively correlated to BMI and percent body fat. These results suggest that faecal microbiota is related to insulin sensitivity and secretion in overweight or obese adults. These correlations are distinct although partially overlapping, suggesting different pathophysiological pathways. Our findings can inform future trials aiming to manipulate gut microbiome to improve insulin sensitivity and secretion and prevent type 2 diabetes.
Highlights
The worldwide dramatic rise in the prevalence of both obesity [1] and diabetes [2] calls for further studies to improve our understanding of mechanisms involved in the development of these conditions and to discover therapeutic approaches to reduce the related health and economic burdens
To the best of our knowledge, this is the first study examining the correlations of faecal microbiota with both insulin sensitivity and insulin secretion in individuals at high risk for diabetes
The abundance of Dialister was negatively correlated with insulin sensitivity as well as positively with insulin concentrations both in the fasting and glucose-stimulated states
Summary
The worldwide dramatic rise in the prevalence of both obesity [1] and diabetes [2] calls for further studies to improve our understanding of mechanisms involved in the development of these conditions and to discover therapeutic approaches to reduce the related health and economic burdens. Findings mainly from animal and in vitro studies have established some of the underlying mechanisms by which the gut microbiota can alter insulin resistance and risk of diabetes [5,6,12]. LPS promotes the activation of the nuclear factor kappa-B (NFkB) and c-Jun N-terminal kinase (JNK) pathways, both of which have been linked to the development of insulin resistance and impaired insulin signalling in muscle, adipose tissue, liver, and hypothalamus [13]. The activation of FXR results in impaired glucose homeostasis [20], whereas TGR5 activation improves glucose tolerance by increasing GLP-1 [21] and promoting energy expenditure in brown adipose tissue and muscle [22]. We examined differences in microbiota composition in a cohort of non-diabetic overweight or obese adults in whom obesity, insulin sensitivity and insulin secretion were characterised using dual X-ray absorptiometry, hyperinsulinaemic-euglycaemic clamps and intravenous glucose tolerance tests, respectively
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