(P06-29-26) Whole Wheat Improves Glucose Tolerance While Favorably Modulating Gut Microbial Composition in Individuals With Prediabetes: A Randomized Crossover Trial

Objectives: Randomized controlled trials (RCTs) examining whole grains on glycemic control have yielded equivocal outcomes, potentially due to inter‑individual dietary and biological variability that influences glycemic responses to whole grains. We hypothesized that whole wheat bread would improve glycemia by modulating gut prebiotic and antimicrobial activities.

Methods: Adults with prediabetes (n = 39; 40.5 ± 2.0 y; 34.7 ± 0.9 kg/m²) completed a crossover RCT consuming 160 g/d of whole wheat bread (WHEAT) or refined bread as part of a fully controlled 2-wk diet. Fasting plasma and fecal samples were collected at baseline and day 14 of each intervention period, and a 3-h oral glucose tolerance test was conducted on day 14. Plasma glucose and insulin were assessed by spectrophotometry, and fecal microbiota composition was characterized by 16S rRNA sequencing.

Results: Compliance with test breads exceeded 98%. Fasting glucose and insulin decreased during both study arms (P_time < 0.005). AUC_{0–180 min} for postprandial Δglucose was lower in WHEAT (p = 0.03), while Δinsulin tended to be higher (p = 0.06). While α- and β-diversity were unaffected, and exploratory analysis indicated microbial shifts during WHEAT. Lachnoclostridium, Streptococcus, Mediterraneibacter, and Pseudomonadota decreased (P_time < 0.04), whereas Agathobacter, Agathobaculum, and the Lachnospiraceae NK4A136 group increased (P_time < 0.04). Agathobaculum abundance correlated with lower Δglucose AUC_{0–180 min} (r = –0.34, p = 0.03), while Lachnoclostridium correlated positively (r = 0.35, p = 0.027).

Conclusions: Whole wheat bread improved glucose tolerance in adults with prediabetes.

Microbial shifts toward beneficial fermentative genera and decreases in dysbiosis‑associated populations, along with their associations with glycemic control, support microbial functional capacity to shape individual glycemic responses to whole grains. Ongoing metabolite analyses aim to clarify mechanisms underlying inter-individual variability in glycemic control.

Funding Sources: USDA-AFRI 2022-67017-37187