Fig. 5

Sulfonylurea drugs: use stratifies glucose control endpoints, and some formulation strains are inhibited by SFUs in a drug-specific pattern. a Participant change in HbA1c versus study arm, with metabolomics-enhanced SFU drug usage status indicated by color shading. Gold and black color respectively indicate participants that are believed to have used, or not-used, SFU drug during the study as determined from the clinical record, direct observation of SFU in blood plasma, or both. Cross-bar indicates the value of each sub-group mean. b Summary of the re-estimation of glucose control endpoint statistics in the comparison of WBF-011 group (the five strain formulation) versus Placebo group (shown as WBF-011 - Placebo). ‘Per protocol’ refers to the cohort that successfully completed the study, as described previously [21]. ‘No SFU: Clinic’ refers to the results of between-group comparison among participants not known to use SFU according to the clinical record. This is equivalent to the confounding effect described in the original study. ‘No SFU: Clinic or Plasma’ is the same analysis, but with additional participants omitted where SFU was detected in metabolomics. c Representative growth curves (OD 600 nm versus time in hours) for formulation strains with or without the presence of the indicated SFU drug in mVEG (AMUC), mPYG (CBEI, CBUT), or PYG (BINF, EHAL). Panel rows from top to bottom represent a 2-fold increasing concentration of the indicated SFU, with the millimolar concentration labeled in the top-left corner. Each black curve is a separate replicate inoculated at the same time as other curves for that strain, including positive controls. Green and blue regions indicate the range occupied by no-SFU positive controls in the same medium, with or without the final volumetric fraction of DMSO (3% for CBUT, 2% for all others), respectively. OD 600 nm values have been spline-smoothed and baseline-subtracted. To improve interpretability, each curve has been filtered to display just the period of continuous monotonic increase (growth)