A low FODMAP (fermentable oligo-, di-, mono-saccharides and polyols) diet is often recommended in patients with quiescent inflammatory bowel disease (IBD) who experience irritable bowel syndrome-like symptoms. Concerns that the diet could exacerbate or re-activate inflammation by modifying microbiota fermentation and short-chain fatty acid (SCFA) production have been raised. This study examined the effect of altering dietary FODMAP content on inflammation and SCFA production in models of active and quiescent IBD. C57BL/6 mice were given 3% dextran sulfate sodium (DSS) in drinking water for 5-days and allowed to recover for 5-days (active-IBD model) or 3-weeks (post-inflammatory model). Following recovery, DSS-treated or control mice were randomized to a 2-week low FODMAP (0.51g/100g total FODMAP) or high FODMAP (4.10g/100g) diet. Diets mimicked human consumption and contained fructose, sorbitol, galacto-oligosaccharide and fructan. Colons were assessed for myeloperoxidase (MPO) activity, histological scores by blinded reviewers, and supernatants were collected for perforated patch-clamp recordings of dorsal root ganglion mouse neurons, a functional assay for proinflammatory cytokines. Cecum contents were analysed for SCFA (acetic, propionic, butyric, pentanoic acids) and branched-chain fatty acids (BCFA; isobutyric, isovaleric acids). Statistical analysis used one-way ANOVA with bonferroni. Inflammatory markers were similar in mice receiving the low and high FODMAP diets within each treatment group (Fig 1A; MPO: low vs high FODMAP respectively, mean±SD, control 0.1±0.2vs0.0±0.3, p>0.99; active-IBD 36.9±20.0vs34.9±17.0, p>0.99; post-inflammatory 1.6±2.2vs0.6±0.9, p>0.99. Histological scores: control 0±0vs0±0, p>0.99; active-IBD 4±4vs7±7, p>0.99; post-inflammatory 0.5±1vs0.3±0.5, p>0.99). In the post-inflammatory model, no difference in rheobase occurred during patch-clamp recordings (Fig 1B; 62.4±28.3vs64.9±20.8pA; p>0.99). No differences in cecal total SCFA content were seen between the diets. Differences in BCFA were seen with the low FODMAP diet in the active-IBD and post-inflammatory groups but not in the control group (control 0.2±0.0vs0.1±0.1nmol/mg, p=0.99; active-IBD 0.3±0.1vs0.2±0.0, p=0.00; post-inflammatory 0.3±0.0vs0.1±0.0, p=0.00), suggesting proteolytic fermentation. A short-term low FODMAP diet shifts the microbiota toward more proteolytic fermentation. In this model, the low FODMAP diet does not seem to lead to exacerbation of overt inflammation. Figure 1A Myeloperoxidase activity, B patch-clamp recordings did not differ between diets CCC, CIHRCanadian Nutrition Society