Short-Chain Fructooligosaccharides Improve Gut Microbiota Composition in Patients with Type 2 Diabetes. A randomized, Open-Label, Controlled Pilot Clinical Trial. Gissel García1, Duniesky Martínez2, Josanne Soto3, Lays Rodríguez4, Maricela Nuez5, Noraika Domínguez5, Emilio F. Buchaca4, Carlos Hernández2, Alina Sobrino2, Enrique R. Pérez2, Raúl J. Cano6* Abstract In this study, the impact of KestoMix, a syrup containing short-chain fructooligosaccharides (scFOS) mainly 1-kestose, on clinical parameters and gut microbiota composition in type 2 diabetes (T2DM) patients was investigated. The study was conducted as a randomized, open label, controlled clinical trial involving 60 participants. The control group consumed microcrystalline cellulose capsules, while the KestoMix group consumed KestoMix (7.2 g) twice a day for 12 weeks. Stool and blood samples were collected from all the subjects. The gut microbial composition in feces was analyzed for 20 subjects by next-generation sequencing of the V3–V4 region of the bacterial 16S rRNA gene. KestoMix did not significantly modify the basal clinical parameters associated with T2DM, but it significantly reduced serum LDL-c concentration at week 12. In terms of gut microbial composition, the presence of Firmicutes was higher than Bacteroidetes in both groups, but KestoMix intake resulted in a reduction in the Firmicutes/Bacteroidetes ratio. Also, a significant increase (p=0.046) in the Bacteroidetes/Proteobacteria ratio compared to the control group was observed at day 84. Furthermore, KestoMix intake significantly stimulated the increase in Bifidobacterium, as well as Blautia and Lactobacillus) (p=0.007, p=0.034 and p=0.016, respectively). While the alpha diversity of gut microbial composition was reduced after KestoMix intake, there was a change in the existing taxonomic proportions. Overall, this study highlights the positive impact of KestoMix on gut microbiota in T2DM patients. The bifidogenic effect of KestoMix may provide long-term benefits in complications associated with T2DM and other dysbiosis. Keywords: Fructooligosaccharides, prebiotic, type 2 diabetes mellitus, metagenomics sequencing, gut microbiota Metabolic Shifting Probiotic in Type 2 Diabetes Mellitus Management:Randomized Clinical Trial Gissel García1`a, Josanne Soto1b, Lays Rodríguez1c, Maricela Nuez4, Noraika Domínguez1d, Emilio F. Buchaca1c, DunieskyMartínez2, Rolando J Gómez1b, Yohanka Ávila1c, Martha R. Carlin3, Raúl J. Cano3,4* We report the results of a 12-week, double blind, placebo-controlled study designed to evaluate the symbiotic supplement BiotiQuest™ Sugar Shift (SS) in Cuban type 2 diabetes mellitus patients. The clinical parameters, including fasting and post-prandial (2h) glucose, hemoglobin A1c, a lipid panel, insulin, and creatinine were assessed using an autoanalyzer Cobas 6000, from Roche Diagnostic. Additionally, serum lipopolysaccharide levels were measured using the commercial kit ToxinSensorTM Endotoxin Detection System (GeneScript). The microbiome analysis for biodiversity was determined by 16S amplicon sequencing of the variable region V3-V4 of the 16S rRNA gene. Fasting glucose and Insulin levels decreased significantly at day 84 as compared to day 1 in the treated group compared to control group (p=0.006 and p=0.015 respectively). The principal variable, the Hb A1c, did not show significant movement in the treated group. However, decrease levels of LPS was significant in the treated group (p=0.019). These results were interpreted as the outcome of favorable microbiome favorably changes during the course of the treatment for 12 weeks. Additionally, the microbiome analysis showed significant changes in Alpha diversity in the treated group between day 1 and day 84 (p=0.0089) and also between both study groups after 84 days (0.011). Taxonomic and functional biomarkers revealed significant differences between the Day 1 and Day 84 associated to different bacteria and biomarker genes. These were primarily involved in the production of short chain fatty acids and concomitant reduction of serum LPS inflammation. In conclusion, SS, in this study, was shown to be a suitable nutritional supplement for the control of T2DM and the reduction of biomarkers associated with this dysbiosis. The positive impact in the reduction of inflammatory processes in gut suggests that this supplement can be effective in the control of inflammation in other metabolic dysbioses. Keywords: Diabetes, Probiotics, clinical trials, inflammation, insulin resistance, fasting glucose, lipopolysaccharides (LPS).