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This randomized controlled trial enrolled 71 adults with metabolic syndrome and randomized them to a five-day modified Buchinger-style fast followed by a modified DASH diet versus DASH diet alone. Investigators measured 16S rRNA gut microbiome composition, ambulatory blood pressure, antihypertensive medication requirements, and standard cardiometabolic biomarkers at baseline, immediately post-fast, and at three months follow-up. The fasting plus DASH arm showed greater reductions in systolic blood pressure, in the requirement for antihypertensive medications, and in body-mass index at three months than the DASH-only arm. Gut microbiome analysis identified specific bacterial taxa — including changes in genera linked to short-chain fatty acid production and to microbial pathways relevant to host metabolic regulation — that responded to the fast, with changes that partly persisted into the post-fast period. The paper is one of the few human RCTs to combine a multi-day fasting intervention with comprehensive microbiome characterization and clinically meaningful blood pressure endpoints.

This study established a foundational point in microbiome research: dietary changes alter gut microbial composition rapidly and reproducibly. Ten participants alternated between an entirely animal-based diet (meat, eggs, cheese) and an entirely plant-based diet (grains, legumes, fruits, vegetables) for five days each. Microbiome composition shifted within 24 hours of dietary change and reverted within 48 hours of returning to baseline diet. The animal-based diet specifically increased the abundance of bile-tolerant microorganisms (Bilophila wadsworthia, Alistipes putredinis, Bacteroides) and decreased the abundance of Firmicutes that metabolize plant polysaccharides. Functional metagenomic analysis confirmed corresponding shifts in microbial gene expression. The paper is the canonical reference for the rapid-response biology of the human gut microbiome to dietary substrate change and for the bidirectional, plastic nature of these shifts.