Unique Gut Microbiome Signatures Depict Diet-Versus Genetically Induced Obesity in Mice
Ravinder Nagpal, Sidharth P. Mishra, Hariom Yadav
Abstract
The gut microbiome plays an important role in obesity and Type 2 diabetes (T2D); however, it remains unclear whether the gut microbiome could clarify the dietary versus genetic origin of these ailments. Moreover, studies examining the gut microbiome in diet- versus genetically induced obesity/T2D in the same experimental set-up are lacking. We herein characterized the gut microbiomes in three of the most widely used mouse models of obesity/T2D, i.e., genetically induced (leptin-deficient i.e., Lepob/ob; and leptin-receptor-deficient i.e., Lepdb/db) and high-fat diet (HFD)-induced obese (DIO)/T2D mice, with reference to their normal chow-fed (NC) and low-fat-diet-fed (LF) control counterparts. In terms of β-diversity, Lepob/ob and Lepdb/db mice showed similarity to NC mice, whereas DIO and LF mice appeared as distinct clusters. The phylum- and genus-level compositions were relatively similar in NC, Lepob/ob, and Lepdb/db mice, whereas DIO and LF mice demonstrated distinct compositions. Further analyses revealed several unique bacterial taxa, metagenomic functional features, and their correlation patterns in these models. The data revealed that obesity/T2D driven by diet as opposed to genetics presents distinct gut microbiome signatures enriched with distinct functional capacities, and indicated that these signatures can distinguish diet- versus genetically induced obesity/T2D and, if extrapolated to humans, might offer translational potential in devising dietary and/or genetics-based therapies against these maladies.