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.
- diabetes mellitus, Type 2
- glycated hemoglobin A
- fatty acids
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FP and PM are joint first authors.
Contributors FP and JB participated in study design, statistical analysis, and manuscript preparation and review. PM participated in study design, study logistics, data analysis, and manuscript preparation and review. AC and AD participated in manufacture of study product. CC participated in study design and manuscript review. JE and MI participated in study design, study logistics, and manuscript review. JG participated in study logistics and fecal analyses. NJ oversaw the fecal analyses. WTL participated in data analysis. MN and ST participated in fecal analysis. MaSc oversaw manufacture of study product. MiSo participated in data analysis. BS participated in manufacture of study product. OK participated in study design, study conduct, data analysis, and manuscript preparation and review.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests All authors are employees and stock/stock option shareholders of Pendulum Therapeutics, Inc (formerly known as ‘Whole Biome Inc.’). OK owns stock in GlySens, Inc, has stock options in ViaCyte, Inc, and is a consultant to NuSirt BioPharma, Circius, and NanoPrecision Medical.
Patient consent for publication Not required.
Ethical Approval This study was approved by the Allendale institutional Review Board (30 Neck Road, Old Lyme, CT, 06371) and informed consent was obtained from each subject prior to participation.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available in a public, open access repository. Data and reproducible examples of data analysis are made available at the following public git-tracked repository: https://github.com/wholebiome/NCT03893422.