It has been shown that gut dysbiosis can be associated with the development of type 2 diabetes mellitus (T2DM). Consequently, intervention with probiotics may be a useful approach to improve metabolic variables in diabetes. The present study aimed to evaluate the efficacy of L. paracasei HII01 on glycemia in T2DM patients. In a randomized, double-blind, placebo-controlled study, 50 participants were allocated to receive L. paracasei HII01 (50 × 109 CFU/day) or a placebo (corn starch 10 mg/day). Blood and fecal samples were assessed at baseline and at the end of the trial. After 12 weeks of intervention, fasting blood glucose level had significantly decreased in the probiotic group compared with the placebo group. Importantly, probiotic supplementation significantly decreased the plasma levels of LPS, TNF-α, IL-6 and hsCRP compared the placebo group. Additionally, an increase in beneficial bacteria and a decrease in pathogenic bacteria, which related to the improvement of SCFAs, was found following L. paracasei HII01 supplementation. These findings demonstrated that L. paracasei HII01 improved hyperglycemia and inflammatory markers by favorably modifying gut microbiota and subsequently ameliorating the leaky gut and endotoxemia, thereby suggesting a potential role as an adjuvant treatment in type 2 diabetes.

Rice husk (RH) is an agricultural waste obtained from rice milling process. Our previous study demonstrated the optimized process of extracting xylooligosaccharides (XOS), a prebiotic that can support the growth and activity of beneficial gut microbiota, from RH. Accumulated evidences indicate that the composition of gut microbiota is involved in the progression of insulin resistance and diabetes. This study aims to evaluate the antihyperglycemic effect and putative mechanisms of RH-XOS using a diabetic rat model induced by high-fat diet and streptozotocin injection. Diabetic rats were randomly assigned to receive vehicle (DMC), XOS (DM-XOS), metformin (DMM), and a combination of XOS and metformin (DMM-XOS). An additional group of rats were fed with normal diet plus vehicle (NDC) and normal diet plus XOS (ND-XOS). Supplementation with RH-XOS for 12 weeks successfully decreased the fasting plasma glucose, insulin, leptin, and LPS levels in DM-XOS compared with DMC. Likewise, the insulin-stimulated glucose uptake assessed by in vitro study was significantly enhanced in DM-XOS, DMM, and DMM-XOS. The diminished protein expressions of GLUT4 and pAkt Ser473 as well as pAMPK Thr172 were significantly modulated in DM-XOS, DMM, and DMM-XOS groups. Interestingly, RH-XOS supplementation reversed the changed gut permeability, elevated the number of beneficial bacteria, both Lactobacillus and Bifidobacterium spp., and increased SCFAs production. Taken together, the results confirm the efficacy of RH-XOS in achieving good glycemic control in diabetes by maintenance of gut microbiota and attenuation of endotoxemia.The findings reveal the benefits of RH-XOS and open an opportunity to improve its value by its development as a nutraceutical for diabetes. K E Y W O R D Santihyperglycemia, diabetes mellitus, gut microbiota, prebiotic, rice husk, xylooligosaccharides | 429 KHAT-UDOMKIRI eT Al.

Despite the updated knowledge of the impact of gut dysbiosis on diabetes, investigations into the beneficial effects of individual bacteria are still required. This study evaluates the antihyperglycemic efficacy of Lactobacillus paracasei HII01 and its possible mechanisms in diabetic rats. Diabetic rats were assigned to receive vehicle, L. paracasei HII01 (108 CFU/day), metformin 30 (mg/kg) or a combination of L. paracasei HII01 and metformin. Normal rats given vehicle and L. paracasei HII01 were included. Metabolic parameters, including in vitro hemi-diaphragm glucose uptake, skeletal insulin-signaling proteins, plasma lipopolysaccharide (LPS), gut permeability, composition of gut microbiota and its metabolites, as well as short-chain fatty acids (SCFAs), were assessed after 12 weeks of experiment. The results clearly demonstrated that L. paracasei HII01 improved glycemic parameters, glucose uptake, insulin-signaling proteins including pAktSer473, glucose transporter 4 (GLUT4) and phosphorylation of AMP-activated protein kinase (pAMPKThr172), tumor necrosis factor (TNF-α) and nuclear factor-κB (NF-kB) in diabetic rats. Modulation of gut microbiota was found together with improvement in leaky gut, endotoxemia and SCFAs in diabetic rats administered L. paracasei HII01. In conclusion, L. paracasei HII01 alleviated hyperglycemia in diabetic rats primarily by modulating gut microbiota along with lessening leaky gut, leading to improvement in endotoxemia and inflammation-disturbed insulin signaling, which was mediated partly by PI3K/Akt signaling and AMPK activation.

Transforming growth factor beta (TGF-β) is a key factor mediating the intercellular crosstalk between the hematopoietic stem cells and their microenvironment. Here, we investigated the skeletal phenotype of transgenic mice expressing constitutively active TGF-β receptor type I under the control of Mx1-Cre (Mx1;TβRICA mice). μCT analysis showed decreased cortical thickness, and cancellous bone volume in both femurs and mandibles. Histomorphometric analysis confirmed a decrease in cancellous bone volume due to increased osteoclast number and decreased osteoblast number. Primary osteoblasts showed decreased ALP and mineralization. Constitutive TβRI activation increased osteoclast differentiation. qPCR analysis showed that Tnfsf11/Tnfrsf11b ratio, Ctsk, Sufu, and Csf1 were increased whereas Runx2, Ptch1, and Ptch2 were decreased in Mx1;TβRICA femurs. Interestingly, Gli1, Wnt3a, Sp7, Alpl, Ptch1, Ptch2, and Shh mRNA expression were reduced whereas Tnfsf11/Tnfrsf11b ratio was increased in Mx1;TβRICA mandibles. Similarly, osteoclast-related genes were increased in Mx1;TβRICA osteoclasts whereas osteoblast-related genes were reduced in Mx1;TβRICA osteoblasts. Western blot analysis indicated that SMAD2 and SMAD3 phosphorylation was increased in Mx1;TβRICA osteoblasts, and SMAD3 phosphorylation was increased in Mx1;TβRICA osteoclasts. CTSK was increased while RUNX2 and PTCH1 was decreased in Mx1;TβRICA mice. Microindentation analysis indicated decreased hardness in Mx1;TβRICA mice. Our study indicated that Mx1;TβRICA mice were osteopenic by increasing osteoclast number and decreasing osteoblast number, possibly by suppressing Hedgehog signaling pathways.