BACKGROUND AND AIMS: Increased efficiency of energy harvest, due to alterations 
in the gut microbiota (increased Firmicutes and decreased Bacteroidetes), has 
been implicated in obesity in mice and humans. However, a causal relationship is 
unproven and contributory variables include diet, genetics and age. Therefore, 
we explored the effect of a high-fat (HF) diet and genetically determined 
obesity (ob/ob) for changes in microbiota and energy harvesting capacity over 
time.
METHODS: Seven-week-old male ob/ob mice were fed a low-fat diet and wild-type 
mice were fed either a low-fat diet or a HF-diet for 8 weeks (n=8/group). They 
were assessed at 7, 11 and 15 weeks of age for: fat and lean body mass (by NMR); 
faecal and caecal short-chain fatty acids (SCFA, by gas chromatography); faecal 
energy content (by bomb calorimetry) and microbial composition (by metagenomic 
pyrosequencing).
RESULTS: A progressive increase in Firmicutes was confirmed in both HF-fed and 
ob/ob mice reaching statistical significance in the former, but this phylum was 
unchanged over time in the lean controls. Reductions in Bacteroidetes were also 
found in ob/ob mice. However, changes in the microbiota were dissociated from 
markers of energy harvest. Thus, although the faecal energy in the ob/ob mice 
was significantly decreased at 7 weeks, and caecal SCFA increased, these did not 
persist and faecal acetate diminished over time in both ob/ob and HF-fed mice, 
but not in lean controls. Furthermore, the proportion of the major phyla did not 
correlate with energy harvest markers.
CONCLUSION: The relationship between the microbial composition and energy 
harvesting capacity is more complex than previously considered. While 
compositional changes in the faecal microbiota were confirmed, this was 
primarily a feature of high-fat feeding rather than genetically induced obesity. 
In addition, changes in the proportions of the major phyla were unrelated to 
markers of energy harvest which changed over time. The possibility of microbial 
adaptation to diet and time should be considered in future studies.