Obesity and type 2 diabetes (T2D) have been associated with alterations in the gut microbiome. Given that both conditions are commonly manifested together and that ruling out the impact of external confounding factors in microbiome variation is a challenge, scientists struggle with teasing out gut microbiome hallmarks that uniquely characterize each of the two conditions.
Louise Thingholm from Kiel University (CAU) (Germany) and colleagues have found that while obesity is associated with gut microbiome variation, gut microbiome associations with type 2 diabetes are modest.
To better understand the gut microbiome’s role in the progression from obesity to T2D, the authors studied the gut microbiomes of lean non-diabetic (n = 633), obese non-diabetic (n = 494), and obese individuals with T2D (n = 153) from two northern German population cohorts. The different medication taken by patients was taken into account as confounders in statistical analyses.
Compared with lean individuals, those with obesity and normal fasting glucose showed differences in their gut microbiome at compositional (decreased alpha-diversity) and functional levels.
Notable changes in individual gut microbial taxa found in individuals with obesity but not in obese individuals with T2D included a fall in Akkermansia, Faecalibacterium, Oscillibacter, Alistipes.
At the functional level, individuals with non-diabetic obesity showed a decreased capacity for conjugation and superoxide reductase compared with lean non-diabetic people. The latter has previously been suggested as one of the mechanisms by which the gut microbiome may lead to weight gain and insulin resistance in patients with T2D.
In contrast, T2D only had a modest impact on the gut microbiome of obese individuals with T2D, despite an increased abundance of Escherichia/Shigella.
Metagenomic analysis showed associations between dietary nutrients, dietary supplements (multivitamins and minerals), medication (analgesics, antidepressants, antihypertensives, antiphlogistics, and antidiabetic drugs) and the gut microbiome. Together, they all explained a significant amount of variation in the gut microbiome, with small variations explained by each individual variable.
The notable impact of dietary iron on the gut microbiome and its previous link to diabetes prompted scientists to study its impact in a controlled setting in mice. In mice treated over a 7-day period with sufficient or high iron intake, the authors confirmed the causal effect of iron on the gut microbiome, which explained up to 9% of gut microbiome variation.
The fact that medication can have the same level of impact on the gut microbiome as diet has been identified previously in large population studies.
Serum metabolite profiles were associated with both obesity and T2D. Of the 390 metabolites identified, certain ones were specifically associated with obesity and a smaller number were specifically related to T2D. The latter corresponds with findings of the gut microbiome.
On the whole, this study shows that obesity, but not type 2 diabetes, is linked to gut microbiome changes at both taxonomic and functional level. As such, validation of these findings in larger populations, considering external confounders such as different kinds of medication, is warranted.
Thingholm LB, Rühlemann MC, Koch M, et al. Obese individuals with and without type 2 diabetes show different gut microbial functional capacity and composition. Cell Host Microbe. 2019; 26(2):252-64. doi: 10.1016/j.chom.2019.07.004.