There is a growing interest in modulating gut microbiota with diet in the context of obesity. The purpose of the present study was to evaluate the dose-dependent effects of prebiotics (inulin and oligofructose) on gut satiety hormones, energy expenditure, gastric emptying and gut microbiota. Male lean and obese JCR:LA-cp rats were randomised to either of the following: lean 0 % fibre (LC), lean 10 % fibre (LF), lean 20 % fibre (LHF), obese 0 % fibre (OC), obese 10 % fibre (OF) or obese 20 % fibre (OHF). Body composition, gastric emptying, energy expenditure, plasma satiety hormone concentrations and gut microbiota (using quantitative PCR) were measured. Caecal proglucagon and peptide YY mRNA levels were up-regulated 2-fold in the LF, OF and OHF groups and 3-fold in the LHF group. Ghrelin O-acyltransferase mRNA levels were higher in obese v. lean rats and decreased in the OHF group. Plasma ghrelin response was attenuated in the LHF group. Microbial species measured in the Bacteroidetes division decreased, whereas those in the Firmicutes increased in obese v. lean rats and improved with prebiotic intake. Bifidobacterium and Lactobacillus increased in the OHF v. OC group. Bacteroides and total bacteria negatively correlated with percentage of body fat and body weight. Enterobacteriaceae increased in conjunction with glucose area under the curve (AUC) and glucagon-like peptide-1 AUC. Bacteroides and total bacteria correlated positively with ghrelin AUC yet negatively with insulin AUC and energy intake (P,0·05). Several of the mechanisms through which prebiotics act (food intake, satiety hormones and alterations in gut microbiota) are regulated in a dose-dependent manner. The combined effects of prebiotics may have therapeutic potential for obesity.Key words: Inulin: Oligofructose: Satiety response: Gut microbiota Prebiotic fibres represent oligosaccharides that are resistant to human digestive enzymes but can be fermented by bacteria in the caeco-colon (1) . Several studies have demonstrated that supplementing the diet, both standard chow (2) and high fat (3,4) , of rodents with inulin, oligofructose or a combination of the two reduces energy intake and fat mass. Suggestions as to the mechanisms responsible for these effects have included alterations in satiety hormone secretion, delayed gastric emptying, energy dilution, increased energy expenditure and modulation of gut microflora.The intestinal mucosa, primarily in the distal ileum, caecum and colon, contains endocrine L-cells that secrete peptides in response to nutrient stimulus (5 -7) . Of particular interest, with respect to weight loss, are the two L-cell-derived anorexigenic peptides, glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), and the X/A-like cell-derived orexigenic peptide ghrelin. Prebiotics have been shown to increase GLP-1 and PYY in human subjects (8,9) and rodent models (2,3,10 -12) . Expression of proglucagon, the precursor of GLP-1, can be up-regulated by SCFA, the end products of fibre fermentation in the gut (12,13) . Ghrelin...