Abstract
BackgroundIt is well known that the microbiota of high-fat (HF) diet-induced obese mice differs from that of lean mice, but to what extent, this difference reflects the obese state or the diet is unclear. To dissociate changes in the gut microbiota associated with high HF feeding from those associated with obesity, we took advantage of the different susceptibility of C57BL/6JBomTac (BL6) and 129S6/SvEvTac (Sv129) mice to diet-induced obesity and of their different responses to inhibition of cyclooxygenase (COX) activity, where inhibition of COX activity in BL6 mice prevents HF diet-induced obesity, but in Sv129 mice accentuates obesity.ResultsUsing HiSeq-based whole genome sequencing, we identified taxonomic and functional differences in the gut microbiota of the two mouse strains fed regular low-fat or HF diets with or without supplementation with the COX-inhibitor, indomethacin. HF feeding rather than obesity development led to distinct changes in the gut microbiota. We observed a robust increase in alpha diversity, gene count, abundance of genera known to be butyrate producers, and abundance of genes involved in butyrate production in Sv129 mice compared to BL6 mice fed either a LF or a HF diet. Conversely, the abundance of genes involved in propionate metabolism, associated with increased energy harvest, was higher in BL6 mice than Sv129 mice.ConclusionsThe changes in the composition of the gut microbiota were predominantly driven by high-fat feeding rather than reflecting the obese state of the mice. Differences in the abundance of butyrate and propionate producing bacteria in the gut may at least in part contribute to the observed differences in obesity propensity in Sv129 and BL6 mice.
Highlights
It is well known that the microbiota of high-fat (HF) diet-induced obese mice differs from that of lean mice, but to what extent, this difference reflects the obese state or the diet is unclear
Experimental setup and construction of a gut metagenome reference set To distinguish changes in the gut microbiota that occur in response to an obesogenic diet from changes due to obesity development, we exploited the different propensity of BL6 and Sv129 mice to develop diet-induced obesity and their divergent responses to treatment with the general cyclooxygenase inhibitor indomethacin
Bacterial DNA was isolated from fecal samples from 54 mice from the different groups (30 Sv129 mice: 10 fed the LF diet, 10 fed the HF diet, and 10 fed the HF diet supplemented (HFI) diet ; 24 BL6 mice: 7 fed the LF diet, 8 fed the HF diet, and 9 fed the HFI diet) and subjected to whole genome sequencing (WGS) using the Illumina HiSeq2000 platform [24]
Summary
It is well known that the microbiota of high-fat (HF) diet-induced obese mice differs from that of lean mice, but to what extent, this difference reflects the obese state or the diet is unclear. To dissociate changes in the gut microbiota associated with high HF feeding from those associated with obesity, we took advantage of the different susceptibility of C57BL/6JBomTac (BL6) and 129S6/SvEvTac (Sv129) mice to diet-induced obesity and of their different responses to inhibition of cyclooxygenase (COX) activity, where inhibition of COX activity in BL6 mice prevents HF diet-induced obesity, but in Sv129 mice accentuates obesity. Xiao et al Microbiome (2017) 5:43 knockout mice [5], NOD mice [17], ob/ob mice [3], and db/db mice [18, 19] compared with wild-type mice In these mouse models, altered feed intake may contribute to the observed changes in the gut microbiota. We have shown that inhibition of cyclooxygenase activity accentuated HF feeding-induced obesity in the obesityresistant Sv129 mice by reducing diet-induced thermogenesis and induction of UCP1 expression in inguinal white adipose tissue [22], whereas inhibition of cyclooxygenase activity in the normally obesity-prone BL6 mice prevented HF feeding-induced obesity [23]
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