Obesity and type 2 diabetes (T2D) often occur together, and metabolic disease is linked to alterations in the gut microbiome but the changes associated uniquely with obesity versus T2D have been unclear. However, data now show that obesity along with medications and supplements like antihypertensives, antidiabetics, and iron are more associated with these alterations than T2D alone.
The incidence of both obesity and T2D is on the rise worldwide. While not all obese individuals develop T2D, obesity is a risk for the disease and 86% of individuals with T2D are overweight or obese. There are a multitude of factors, both environmental and genetic, that contribute to these diseases. Evidence showing that the gut microbiome plays a role in both obesity and T2D is also growing. However, teasing apart the exact microbes involved and their functions is still incredibly difficult.
To dig through this mess of microbial interactions and host symptoms, researchers from all over the US, Germany, the UK, and Norway designed a study to compare the microbiomes of lean non-obese people, obese-non diabetic people, and obese individuals with T2D. Involved in this work was Microbiome Insights Scientific Advisory Board member Curtis Huttenhower from the Harvard T.H. Chan School of Public Health, Boston (USA).
By separating individuals into these three distinct groups, the team attempted to isolate the changes in gut microbiome composition that are likely due to either obesity or T2D. They analyzed microbial taxonomic and functional profiles of each group and looked at their medical histories, serum metabolomics, biometrics, and dietary data.
Obesity alone was associated with changes to the microbiome composition, individual taxa and functions. Specifically, researchers noted changes in Akkermansia, Faecalibacterium, Oscillibacter, and Alistipes, along with changes in serum metabolites that correlate with gut microbial patterns. When analyzing the data from T2D, however, the changes were more modest. Here they observed nominal increases in Escherichia/Shigella. Interestingly though, dietary factors, medications, and dietary supplements were individually weakly associated with components of the gut microbiome, but in aggregate they “accounted for a significant amount of variation.”
With both obesity and T2D, the presence of so many potential contributing factors does hinder microbiome-related studies. There are always issues regarding statistical power, population structure, and covariates. In this work too, the authors report that the observed differences between groups might be influenced by factors such as insufficient power, phenotypic heterogeneity, microbial ecological variability, confounders such as medication, particular susceptibility to geographic or environmental factors, and broad instability of the altered microbiome of obese individuals.
Despite these limitations the authors do believe that this work “will help to disambiguate the overlapping—but sometimes distinct—microbial effects of the two conditions, in addition to characterization of inter-individual variation in the microbiome as it relates to diet, medications, and other environmental exposures.” They also call on the scientific community to continue to study host-microbiome interactions as an additional route to understanding these metabolic diseases.