Patients with type 2 diabetes (T2D) have decreased butyrate-producing bacteria. We hypothesized that supplementation with butyrate-producing bacteria may exert beneficial effects on T2D. The current study investigated the effects of well-characterized butyrate-producing bacteria Clostridium butyricum CGMCC0313.1 (CB0313.1) on hyperglycemia and associated metabolic dysfunction in two diabetic mouse models. CB0313.1 was administered daily by oral gavage to leptin ^db/db mice for 5 weeks starting from 3 weeks of age, and to HF diabetic mice induced by high fat diet (HFD) plus streptozotocin (STZ) in C57BL/6J mice for 13 weeks starting from 4 weeks of age. CB0313.1 improved diabetic markers (fasting glucose, glucose tolerance, insulin tolerance, GLP-1 and insulin secretion), and decreased blood lipids and inflammatory tone. Furthermore, CB0313.1 reversed hypohepatias and reduced glucose output. We also found that CB0313.1 modulated gut microbiota composition, characterized by a decreased ratio of Firmicutes to Bacteroidetes, reduced Allobaculum bacteria that were abundant in HF diabetic mice and increased butyrate-producing bacteria. Changes in gut microbiota following CB0313.1 treatment were associated with enhanced peroxisome proliferator–activated receptor-γ (PPARγ), insulin signaling molecules and mitochondrial function markers. Together, our study suggests that CB0313.1 may act as a beneficial probiotic for the prevention and treatment of hyperglycemia and associated metabolic dysfunction.

Background and Purpose: Acute pancreatitis (AP) is a common acute abdominal condition, frequently associated with intestinal barrier dysfunction, which aggravates AP retroactively. Butyrate exhibits anti‐inflammatory effects in a variety of inflammatory diseases. However, its potential beneficial effect on AP and the underlying mechanisms have not been investigated.Experimental Approach: Experimental AP was induced by caerulein hyperstimulation in wild‐type and GPR109A^−/− mice. Sodium butyrate was administered intragastrically for 7 days prior to caerulein hyperstimulation. Anti‐inflammatory mechanisms of butyrate were further investigated in peritoneal macrophages.Key Results: Butyrate prophylaxis attenuated AP as shown by reduced serum amylase and lipase levels, pancreatic oedema, myeloperoxidase activity, and improved pancreatic morphology. Amelioration of pancreatic damage by butyrate was associated with reduced levels of TNF‐α, IL‐6, and CCL2 and suppressed activation of the NLRP3 inflammasome in both pancreas and colon. Further, butyrate ameliorated pancreatic inflammation by suppressing interactions between histone deacetylase 1 (HDAC1) and AP1 and STAT1 with increased histone acetylation at H3K9, H3K14, H3K18, and H3K27 loci, resulting in suppression of NLRP3 inflammasome activation and modulation of immune cell infiltration in pancreas. Additionally, butyrate mediated STAT1/AP1‐NLRP3 inflammasome suppression via HDAC1 inhibition was demonstrated in peritoneal macrophage. In colon, butyrate inhibited NLRP3 inflammasome activation via GPR109A. Accordingly, the modulatory effects of butyrate on AP, AP‐associated gut dysfunction, and NLRP3 inflammasome activation were diminished in GPR109A^−/− mice.Conclusion and Implications: Our study dissected tissue‐specific anti‐inflammatory mechanisms of butyrate during AP, suggesting that increased colonic levels of butyrate may be a strategy to protect against AP.

Recent evidence indicates that indigenous Clostridium species induce colonic regulatory T cells (Tregs), and gut lymphocytes are able to migrate to pancreatic islets in an inflammatory environment. Thus, we speculate that supplementation with the well-characterized probiotics Clostridium butyricum CGMCC0313.1 (CB0313.1) may induce pancreatic Tregs and consequently inhibit the diabetes incidence in non-obese diabetic (NOD) mice. CB0313.1 was administered daily to female NOD mice from 3 to 45 weeks of age. The control group received an equal volume of sterile water. Fasting glucose was measured twice a week. Pyrosequencing of the gut microbiota and flow cytometry of mesenteric lymph node (MLN), pancreatic lymph node (PLN), pancreatic and splenic immune cells were performed to investigate the effect of CB0313.1 treatment. Early oral administration of CB0313.1 mitigated insulitis, delayed the onset of diabetes and improved energy metabolic dysfunction. Protection may involve increased Tregs, rebalanced Th1/Th2/Th17 cells and changes to a less proinflammatory immunological milieu in the gut, PLN and pancreas. An increase of α4β7+ (the gut homing receptor) Tregs in the PLN suggests that the mechanism may involve increased migration of gut-primed Tregs to the pancreas. Furthermore, 16S rRNA gene sequencing revealed that CB0313.1 enhanced the Firmicutes/Bacteroidetes ratio, enriched Clostridium-subgroups and butyrate-producing bacteria subgroups. Our results provide the basis for future clinical investigations in preventing type 1 diabetes by oral CB0313.1 administration.

Clinical gestational diabetes mellitus (GDM) is frequently associated with hyperlipidemia comorbidity. Altered human gut microbiome has been linked to GDM and hyperlipidemia, respectively but not the comorbid condition. We hypothesize that the occurrence of hyperlipidemia with GDM may be characterized by distinguishable gut microbiome and blood metabolomic patterns. We presented comprehensive microbiomic coupled with lipidomics analyses to characterize gut microbiota and lipometabolism of plasma samples in women with GDM only, hyperlipidemia only and those with diabetes plus hyperlipidemia, and to explore association of the gut microbiota composition with blood lipid profiles and clinical parameters of gestational diabetes with or without commodity. We found that the relative abundance of bacterial taxa Streptococcus, Faecalibacterium, Veillonella, Prevotella, Haemophilus and Actinomyces was significantly higher in diabetes plus hyperlipidemia cohorts. Moreover, several bacteria were correlated with fasting plasma glucose and blood lipid levels of the participants with GDM and hyperlipidemia. The altered plasma lipidome in subjects with diabetes plus hyperlipidemia suggested that characteristic blood lipid profiles were associated with the pathogenesis of gestational diabetes plus hyperlipidemia. Collectively, this study provides insights on changes in fecal microbiota and plasma lipidome to predict and characterize the development of gestational diabetes with lipid metabolic abnormality.