P1337 High fat diet drives increased dysbiosis in IBD compared to healthy controls

Abstract Background High fat diets (HFD), consisting of low fibre intake and high fat are associated with increased IBD risk. Industrialised diets have known impacts on host health but also impact the gut microbiota1; known to be altered in IBD. Whilst fat is primarily digested in the upper GI tract excess fat travels to the colon, the hub of microbial activity. In this study, microbial community changes in response to HFD were compared in a healthy and IBD patient donor using in vitro continuous culture chemostats. Methods Stool from a healthy donor and a de novo, treatment naive IBD patient were used to seed independent bioreactors. Standard diet was fed until microbial stabilisation followed by 14 days of HFD. Standard diet was then resumed for a 14-day recovery period. Daily sampling was used to assess changes in microbial composition (16S rRNA amplicon sequencing) and function (short chain fatty acids (SCFA) measured by gas-chromatography mass spectrometry). Results Despite comparable bacterial densities at stability the IBD vessel had higher total SCFA output compared to healthy. SCFA profiles were unique between donors with higher acetate and propionate concentration in the IBD vessel (p<0.0086). Butyrate at stability, however, was higher in the healthy vessel (p=0.025). HFD resulted in a depletion of acetate and propionate in both donors and an increase in isobutyrate, isovalerate, heptanoate and octanoate. Following transfer back to standard diet, the healthy vessel remained depleted of propionate (p= 0.0009) and butyrate remained significantly depleted in the IBD vessel (p= 0.0034) and did not recover (stable: recovery; p<0.0001). Healthy only: HFD significantly lowered microbial (alpha) diversity by observed and Shannon metrics (p<0.034) but was unchanged in Chao1 index. By recovery alpha diversity realigned with the stable phase. Beta diversity showed unique composition across each experimental phase (p<0.02). HFD saw a depletion of Faecalibacterium and Blautia in favour of Escherichia-Shigella and Parasutterella genera. Sequence analysis of the IBD vessel is underway. Conclusion HFD affected both HC and IBD microbial communities; isovalerate and isobutyrate levels increased indicating greater amino acid (protein) metabolism by community members. Higher levels of heptanoate and octanoate are indicative of increased fatty acid degradation. The healthy donor had a more robust recovery with only 5 SCFAs remaining altered. In comparison, 8 metabolites remaining altered in IBD with a dramatic impact on butyrate production highlighting the greater fragility in the IBD microbiome. The findings support the need for further mechanistic understanding of the role of diet and microbial changes in IBD. References 1.Agans R, Gordon AH, Kramer DL, Pérez-Burillo S, Rufián-Henares JÁ, Paliy O. Dietary Fatty Acids Sustain the Growth of the Human Gut Microbiota. Applied and Environmental Microbiology. 2018;84(21). doi:10.1128/aem.01525-18