Increased circulating butyrate and ursodeoxycholate during probiotic intervention in humans with type 2 diabetes.

BACKGROUND: An increasing body of evidence implicates the resident gut microbiota as playing a critical role in type 2 diabetes (T2D) pathogenesis. We previously reported significant improvement in postprandial glucose control in human participants with T2D following 12-week administration of a 5-strain novel probiotic formulation ('WBF-011') in a double-blind, randomized, placebo controlled setting (NCT03893422). While the clinical endpoints were encouraging, additional exploratory measurements were needed in order to link the motivating mechanistic hypothesis - increased short-chain fatty acids - with markers of disease. RESULTS: Here we report targeted and untargeted metabolomic measurements on fasting plasma (n = 104) collected at baseline and end of intervention. Butyrate and ursodeoxycholate increased among participants randomized to WBF-011, along with compelling trends between butyrate and glycated haemoglobin (HbA1c). In vitro monoculture experiments demonstrated that the formulation's C. butyricum strain efficiently synthesizes ursodeoxycholate from the primary bile acid chenodeoxycholate during butyrogenic growth. Untargeted metabolomics also revealed coordinated decreases in intermediates of fatty acid oxidation and bilirubin, potential secondary signatures for metabolic improvement. Finally, improvement in HbA1c was limited almost entirely to participants not using sulfonylurea drugs. We show that these drugs can inhibit growth of formulation strains in vitro. CONCLUSION: To our knowledge, this is the first description of an increase in circulating butyrate or ursodeoxycholate following a probiotic intervention in humans with T2D, adding support for the possibility of a targeted microbiome-based approach to assist in the management of T2D. The efficient synthesis of UDCA by C. butyricum is also likely of interest to investigators of its use as a probiotic in other disease settings. The potential for inhibitory interaction between sulfonylurea drugs and gut microbiota should be considered carefully in the design of future studies.

Prognosis of MGMT -Positive Gene in Patients with Brain Tumors of Grade III and Grade IV.

Sumit GoyalObjective To evaluate MGMT gene positivity is associated with better survival in patients diagnosed with brain tumor World Health Organization (WHO) grades III and IV Material and Methods Single-institute restrospective study. A total of 80 patients were enrolled, all underwent surgery either total or subtotal excision of the tumor and MGMT gene testing on tumor tissue by RT-PCR. All received adjuvant radiation (60 Gy/30 fractions, 5 fractions/week) with concurrent temozolomide (75 mg/m 2 ), followed by 12 cycles of adjuvant temozolomide (150 mg/m 2 1st cycle followed by 200 mg/m 2 ) with regular follow-up. Results A total of 80 patients, 75 underwent subtotal excision, 27 were WHO grade III vs. 48 WHO grade IV. Five underwent total excision 1 was WHO grade III vs. 4 WHO grade IV. The median PFS and OS in five patients in total excision in grade III patient was 9.0 and 20 compared with Grade IV, where the median PFS and OS was 8.8 and 17.8 months. Out of 75 patients in the subtotal group median PFS and OS, respectively, in Grade III group was 9.1 and 19.3 and, WHO grade IV with median PFS of 8.8 and OS of 18.8. Conclusion MGMT gene positivity is a prognostic factor in grade III and IV brain tumor.

Butyrate-producing human gut symbiont, Clostridium butyricum, and its role in health and disease.

Clostridium butyricum is a butyrate-producing human gut symbiont that has been safely used as a probiotic for decades. C. butyricum strains have been investigated for potential protective or ameliorative effects in a wide range of human diseases, including gut-acquired infection, intestinal injury, irritable bowel syndrome, inflammatory bowel disease, neurodegenerative disease, metabolic disease, and colorectal cancer. In this review we summarize the studies on C. butyricum supplementation with special attention to proposed mechanisms for the associated health benefits and the supporting experimental evidence. These mechanisms center on molecular signals (especially butyrate) as well as immunological signals in the digestive system that cascade well beyond the gut to the liver, adipose tissue, brain, and more. The safety of probiotic C. butyricum strains appears well-established. We identify areas where additional human randomized controlled trials would provide valuable further data related to the strains' utility as an intervention.

Improvements to postprandial glucose control in subjects with type 2 diabetes: a multicenter, double blind, randomized placebo-controlled trial of a novel probiotic formulation.

INTRODUCTION: A growing body of evidence suggests that specific, naturally occurring gut bacteria are under-represented in the intestinal tracts of subjects with type 2 diabetes (T2D) and that their functions, like gut barrier stability and butyrate production, are important to glucose and insulin homeostasis. The objective of this study was to test the hypothesis that enteral exposure to microbes with these proposed functions can safely improve clinical measures of glycemic control and thereby play a role in the overall dietary management of diabetes. RESEARCH DESIGN AND METHODS: We evaluated whether a probiotic comprised of these anaerobic bacteria would enhance dietary management by (1) manufacturing two novel probiotic formulations containing three (WBF-010) or five (WBF-011) distinct strains in a Current Good Manufacturing Practice (cGMP) facility, (2) establishing consistent live-cell concentrations, (3) confirming safety at target concentrations dispensed in both animal and human studies and (4) conducting a 12-week parallel, double-blind, placebo-controlled, proof-of-concept study in which subjects previously diagnosed with T2D (n=76) were randomly assigned to a two times a day regimen of placebo, WBF-010 or WBF-011. RESULTS: No safety or tolerability issues were observed. Compared with the placebo group, subjects administered WBF-011 (which contains inulin, Akkermansia muciniphila, Clostridium beijerinckii, Clostridium butyricum, Bifidobacterium infantis and Anaerobutyricum hallii) significantly improved in the primary outcome, glucose total area under the curve (AUC): -36.1 mg/dL/180 min, p=0.0500 and also improved in secondary outcomes, glycated hemoglobin (A1c): -0.6, glucose incremental-AUC: -28.6 mg/dL/180 min. CONCLUSIONS: To our knowledge, this is the first randomized controlled trial to administer four of the five strains to human subjects with T2D. This proof-of-concept study (clinical trial number NCT03893422) shows that the intervention was safe and well tolerated and that supplementation with WBF-011 improves postprandial glucose control. The limited sample size and intersubject variability justifies future studies designed to confirm and expand on these observations.

Possible Correlation of Transfusion Transmitted Diseases with Rh type and ABO Blood Group System.

BACKGROUND: Screening of blood is mandatory for transfusion transmitted diseases and is routinely done in the blood banks. As blood is the major source transmission of hepatitis B, hepatitis C, human immunodeficiency virus & many other diseases the hazards can be minimised by effective donor selection and screening. AIM: To find out the correlation between the transfusion transmitted diseases and blood groups and the seroprevalence of HIV, HBV, HCV & syphilis among the apparently healthy human blood donors. Study, Setting & Design: This retrospective study was conducted at the blood bank of a tertiary health care teaching centre for a period of four years. MATERIAL AND METHODS: All voluntary and replacement donors reporting to the blood bank were screened for HIV-1 & 2, HBsAg, HCV and Syphilis. Anti-HIV -1 & 2, HBsAg & anti - HCV was tested using the appropriate Enzyme-linked immunosorbent assay (ELISA) technique using micro-elisa kit supplied by J.Mitra & Co.Ltd. The seropositive samples were again tested on ELISA kits of RFCL &/or BIORAD for further confirmation & ruling out any false positive or false negative results. The rapid plasma reagain (RPR) test was used for estimation of syphilis infection. STATISTICAL ANALYSIS: The data entry was carried out using Microsoft office excel worksheet and was analysed by percentage and comparison. RESULTS: Total of 6000 donors were screened which included voluntary and replacement donors. Seroprevalence of HIV (0.1833 %), HCV (1.28%), HBsAg (1.5833 %) and syphilis (0.4333 %) was detected. In the study done it was also noted - that the NEGATIVE blood groups were more prone to TTIs. Blood group A negative was more prone to TTIs with HIV, HBsAg and VDRL while blood group B negative was more affected by HCV. CONCLUSION: Seroprevalence of these infections shows that routine screening is a must for blood and blood product safe transfusion. Do negative blood groups predispose to TTIs? A finding which makes us think….