Increased plasma IL-6 and prevalence of gram-negative Prevotella copri and Bacteroides vulgatus in feces from type 2 diabetes patients

Dysbiosis have been associated with metabolic syndromes, such as obesity, insulin resistance and type 2 diabetes (T2D). The aim of this study was to evaluate intestinal dysbiosis in Brazilian T2D patients and correlate this data with dietary habits, inflammatory cytokines, LPS plasma levels, and clinical data, such as body mass index, fasting blood glucose, glycated hemoglobin (HbA1C), and disease duration. Stool samples were collected for DNA extraction and sequencing V3/V4 regions from bacterial 16S by using Illumina platform. Plasma was used for cytokine and LPS quantification, by CBA flex and ELISA, respectively. Statistical analyzes was performed by Pearson's chi-square or Fishers exact test, Mann-Whitney and Spearman's test. The study included 20 T2D patients (58.9 ± 8.4 years) and 22 control subjects (55.7 ± 8.3 years). Regarding dietary habits, there are no correlations among protein, fat and carbohydrates consumption with gut microbiota relative abundances. On the other hand, we found significant difference (P=0.018) in the probiotics consumption in the healthy control group. Concerning gut microbiota characterization, there were no differences in richness and evenness between two evaluated groups, however, there are significant differences (P<0.01) in the microbiota composition (beta-diversity) between patients and controls. The prevalent phyla in patients were Bacteroidetes (patient reads (P)=47.97%; control reads (C)=46.32%) and Firmicutes (P=43.77%; C=43.92%). The prevalent species in feces from T2D patients were Prevotella copri (P=19%; C=7%), Bacteroides vulgatus (P=13%; C=18%), Bacteroides rodentium (P=9%; C=13%), and Bacteroides xylanisolvens (P=8%; C=6%). We observed a negative correlation of Ruminoccocaceae reads with HbA1C percentages (P=0.021, ?=-0.69). Plasma levels of IL-6 were significantly increased in patients (T2D=3.081 ± 0.447 pg/mL; C=1.547 ± 0.141 pg/mL). LPS levels were decreased in patients' plasma (T2D=13.54 ± 0.86 ng/mL; C=16.98 ± 0.79 ng/mL; P=0.009). In summary, we detected dysbiosis in T2D patients with significant differences in overall microbial community between patients and control group. There is a prevalence of gram-negative species in patients' feces, especially Prevotella copri and Bacteroides vulgatus, which are associated with insulin resistance. Further studies are necessary, and in the near future, these bacteria may serve as predictive markers of T2D and could represent a “T2D gut microbiota signature”.