Aberrant intestinal microbiota in individuals with prediabetes

Abstract

Aims/hypothesis Individuals with type 2 diabetes have aberrant intestinal microbiota. However, recent studies suggest that metformin alters the composition and functional potential of gut microbiota, thereby interfering with the diabetes-related microbial signatures. We tested whether specific gut microbiota profiles are associated with prediabetes (defined as fasting plasma glucose of 6.1-7.0 mmol/l or HbA 1c of 42-48 mmol/mol [6.0-6.5%]) and a range of clinical biomarkers of poor metabolic health. Methods In the present case-control study, we analysed the gut microbiota of 134 Danish adults with prediabetes, overweight, insulin resistance, dyslipidaemia and low-grade inflammation and 134 age-and sex-matched individuals with normal glucose regulation. Results We found that five bacterial genera and 36 operational taxonomic units (OTUs) were differentially abundant between individuals with prediabetes and those with normal glucose regulation. At the genus level, the abundance of Clostridium was decreased (mean log 2 fold change −0.64 (SEM 0.23), p adj = 0.0497), whereas the abundances of Dorea, , respectively). The two OTUs that differed the most were a member of the order Clostridiales (OTU 146564) and Akkermansia muciniphila, which both displayed lower abundance among individuals with prediabetes (mean log 2 fold change −1.74 (SEM 0.41), p adj = 2 × 10 −3 and −1.65 (SEM 0.34),, respectively). Faecal transfer from donors with prediabetes or screen-detected, drug-naive type 2 diabetes to germfree Swiss Webster or conventional C57BL/6 J mice did not induce impaired glucose regulation in recipient mice. Conclusions/interpretation Collectively, our data show that individuals with prediabetes have aberrant intestinal microbiota characterised by a decreased abundance of the genus Clostridium and the mucin-degrading bacterium A. muciniphila. Our findings are comparable to observations in overt chronic diseases characterised by low-grade inflammation.

Physical fitness in community‐dwelling older adults is linked to dietary intake, gut microbiota, and metabolomic signatures

“…Contrarily, LF phenotypes had increased levels of these biomarkers and a higher relative abundance of pro‐inflammatory microbial members in the gut, as for example Enterobacterales (Fei & Zhao, ; Khan, Nieuwdorp, & Bäckhed, ). Similar observations have been reported in another cohort of Danish adults (with an age range of 20–65 years), where a reduced abundance of several members of Christensenellaceae and Ruminococcaceae families corresponded with increased levels of proinsulin, HbA1c, triglycerides, and C‐reactive protein (Allin et al, ).…”

Mechanisms of action of metformin with special reference to cardiovascular protection

“…The gut microbiome contains more than 1000‐fold more genes than the human genome, and new research is elucidating its role in health and disease. Alterations in gut microbiota have been associated with dysglycaemia, including on people with prediabetes . Treatment with type 2 diabetes patients with metformin has been shown to alter the relative abundance of individual microbial species within the gut, particularly increasing the number of bacteria that produce short‐chain fatty acids or reduce the abundance of bacteria producing branched amino acids associated with insulin resistance .…”

The Western Diet–Microbiome-Host Interaction and Its Role in Metabolic Disease

“…However, samples from the appendix' of morbidly obese patients showed adverse changes in microbiota composition compared to healthy persons [89]. The connection between gut dysbiosis, inflammation and metabolic disease is also strengthened by human studies showing gut dysbiosis in prediabetic [90], in diabetic [91,92] and in obese patients [93,94].…”