An Intervention With Michigan-Grown Wheat in Healthy Adult Humans to Determine Effect on Gut Microbiota: Protocol for a Crossover Trial.

Background: Daily fiber intake can increase the diversity of the human gut microbiota as well as the abundance of beneficial microbes and their metabolites. Whole-grain wheat is high in fiber.

Objective: This manuscript presents a study protocol designed to understand the effects of different types of wheat on gastrointestinal tract microbes.

Methods: Human adults will consume crackers made from three types of wheat flour (refined soft white wheat, whole-grain soft white wheat, and whole-grain soft red wheat). In this study, participants will alternate between crackers made from refined soft white wheat flour to those made from whole-grain soft white wheat and whole-grain soft red wheat flour. Survey and stool sample collection will occur after 7-day treatment periods. We will assess how wheat consumption affects gastrointestinal bacteria by sequencing the V4 region of 16S rRNA gene amplicons and the inflammatory state of participants' intestines using enzyme-linked immunosorbent assays. The butyrate production capacity of the gut microbiota will be determined by targeted quantitative real-time polymerase chain reaction.

Results: We will report the treatment effects on alpha and beta diversity of the microbiota and taxa-specific differences. Microbiota results will be analyzed using the vegan package in R. Butyrate production capacity and biomarkers of intestinal inflammation will be analyzed using parametric statistical methods such as analysis of variance or linear regression. We expect whole wheat intake to increase butyrate production capacity, bacterial alpha diversity, and abundance of bacterial taxa responsive to phenolic compounds. Soft red wheat is also expected to decrease the concentration of inflammatory biomarkers in the stool of participants.

Conclusions: This protocol describes the methods to be used in a study on the impact of wheat types on the human gastrointestinal microbiota and biomarkers of intestinal inflammation. The analysis of intestinal responses to the consumption of two types of whole wheat will expand our understanding of how specific foods affect health-associated outcomes.

International Registered Report Identifier (irrid): DERR1-10.2196/29046.