Intestinal Microbial and Metabolite Profiling of Mice

1 CNC – Center for Neuroscience and Cell Biology, University of Coimbra, Portugal; 7 [email protected] 8 2 Institute of Microbiology, Faculty of Medicine, University of Coimbra, Portugal 9 3 CEDOC, NOVA Medical School, Universidade NOVA de Lisboa, Rua Camara Pestana, no6, 6A, edifício II, 10 piso 3, 1150-082 Lisbon, Portugal 11 4 CICECO-Department of Chemistry, University of Aveiro, Campus de Santiago, 3810-193 Aveiro, Portugal; 12 e-mail: [email protected] 13 5 UCIBIO@REQUIMTE/Toxicological Laboratory, Biological Science Department, Faculty of Pharmacy, 14 Univeristy of Porto, 4050-313 Porto, Portugal 15 6 Department of Cardiothoracic Surgery and Physiology, Faculty of Medicine, Porto 4200-319, Portugal 16 7 APDP – Portuguese Diabetes Association, Lisbon, Portugal 17 18 † these authors contributed equally to this paper. 19 * Correspondence: [email protected]; Tel.: +351231249181; [email protected], tel:+351234370707 20 21 22 Abstract: Increased sugar intake is implicated in Type-2 diabetes and fatty liver disease. 23 Mechanisms by which glucose and fructose components promote these conditions are unclear. We 24 hypothesize that alterations in intestinal metabolite and microbiota profiles specific to each 25 monosaccharide are involved. Two groups of six adult C57BL/6 mice were fed for 10-weeks with a 26 diet where either glucose or fructose was the sole carbohydrate component (G and F, respectively). 27 A third group was fed with normal chow (N). Fecal metabolites were profiled every 2-weeks by 1H 28 NMR and microbial composition was analysed by real-time PCR (qPCR). Glucose tolerance was also 29 periodically assessed. N, G and F mice had similar weight gains and glucose tolerance. Multivariate 30 analysis of NMR profiles indicated that F mice were separated from both N and G, with decreased 31 butyrate and glutamate and increased fructose, succinate, taurine, tyrosine and xylose. Compared to 32 N and G, F mice showed a shift in microbe populations from gram-positive Lactobacillus spp. to 33 gram-negative Enterobacteria species. Substitution of normal chow carbohydrate mixture by either 34 pure glucose or fructose for 10 weeks did not alter adiposity or glucose tolerance. However, F G and 35 N mice generated distinctive fecal metabolite signatures with incomplete fructose absorption as a 36 dominant feature of F mice. 37