Hui Zhou

BACKGROUND: Although recent studies have indicated that gut microbiome dysbiosis was significantly associated with the onset of type 2 diabetes mellitus (T2DM), information on the role of blood microbiome in T2DM development is scarce. METHODS: Fifty incident T2DM cases and 100 matched non-T2DM controls were selected from a prospective cohort study of "135." The composition of the blood microbiome was characterized using bacterial 16S ribosomal RNA (16S rRNA) gene sequencing from pre-diagnostic blood sample. The amplicons were normalized, pooled, and sequenced on the Illumina MiSeq instrument using a MiSeq Reagent Kit PE300 v3 kit. RESULTS: Totally, 3 000 391 and 6 244 227 high-quality sequences were obtained from T2DM patients and non-T2DM controls, respectively. The mean diversity of the blood microbiome (Simpson, Chao1 and Shannon indices) was not different between two groups at baseline. At genus level, the Aquabacterium, Xanthomonas, and Pseudonocardia were presented with lower abundance, while Actinotalea, Alishewanella, Sediminibacterium, and Pseudoclavibacter were presented with higher abundance among T2DM cases compared to those in non-T2DM controls. As the results shown, participants carried the genus Bacteroides in blood were significantly associated with a decreased risk for T2DM development, with 74% vs 88% (adjusted OR: 0.367, 95% CI: 0.151-0.894). However, participants carried the genus Sediminibacterium have an increased risk for T2DM, with adjusted OR (95% CI) being 14.098 (1.358, 146.330). CONCLUSIONS: Blood microbiome may play an etiology role in the development of T2DM. These findings would be useful to develop microbiota-based strategies for T2DM prevention and control.

OBJECTIVES: Intestinal barrier dysfunction plays an important role in acute necrotizing pancreatitis (ANP) and intestinal microbiota dysbiosis was involved in intestinal barrier failure. Paneth cells protect intestinal barrier and are associated with intestinal microbiota. Here, we investigated changes in intestinal microbiota and antimicrobial peptides of Paneth cells in ileum during ANP. METHODS: Rats with ANP were established by retrograde injection of 3.5% sodium taurocholate into biliopancreatic duct and sacrificed at 24h and 48h, respectively. Injuries of pancreas and distal ileum were evaluated by histopathological score. Intestinal barrier function was assessed by plasma diamine oxidase activity (DAO) and D-lactate. Systemic and intestinal inflammation was evaluated by TNFα, IL-1β and IL-17A concentration by ELISA, respectively. 16S rRNA high throughput sequencing on fecal samples was used to investigate the changes in intestinal microbiota in the ANP group at 48h. Lysozyme and α-defensin5 were measured by real-time PCR, western blot and immunofluoresence. RESULTS: ANP rats had more severe histopathological injuries in pancreas and distal ileum, injured intestinal barrier and increased expression of TNFα, IL-1β and IL-17A in plasma and distal ileum compared with those of the sham-operated (SO) group. Principal component analysis (PCA) showed structural segregation between the SO and ANP groups. Operational taxonomic unit (OTU) number and ACE index revealed decreased microbiota diversity in the ANP group. Taxonomic analysis showed dysbiosis of intestinal microbiota structure. At phyla level, Saccharibacteria and Tenericutes decreased significantly. At genus level, Escherichia-Shigella and Phascolarctobacterium increased significantly, while Candidatus_Saccharimonas, Prevotellaceae_UCG-001, Lachnospiraceae_UCG-001, Ruminiclostridium_5 and Ruminococcaceae_UCG-008 decreased significantly. Lysozyme and α-defensin5 mRNA expression levels decreased significantly in ANP group at 48h. Protein expression of lysozyme decreased in ANP groups at 24h and 48h. Meanwhile, the relative abundance of Escherichia-Shigella correlated inversely with the decrease in lysozyme. CONCLUSION: The disorder in intestinal microbiota and decreases of Paneth cell antimicrobial peptides might participate in the pathogenesis of intestinal barrier dysfunction during ANP.