Abstract

Dietary interventions to manipulate the human gut microbiome for improved health have received increasing attention. However, their design has been limited by a lack of understanding of the quantitative impact of diet on a host’s microbiota. We present a highly controlled diet perturbation experiment in a healthy, human cohort in which individual micronutrients are spiked in against a standardized background. We identify strong and predictable responses of specific microbes across participants consuming prebiotic spike-ins, at the level of both strains and functional genes, suggesting fine-scale resource partitioning in the human gut. No predictable responses to non-prebiotic micronutrients were found. Surprisingly, we did not observe decreases in day-to-day variability of the microbiota compared to a complex, varying diet, and instead found evidence of diet-induced stress and an associated loss of biodiversity. Our data offer insights into the effect of a low complexity diet on the gut microbiome, and suggest that effective personalized dietary interventions will rely on functional, strain-level characterization of a patient’s microbiota.

Highlights

  • A quantitative understanding of the forces that shape the composition of the microbiota in vivo is a prerequisite to rationally engineering or manipulating it toward a favorable clinical outcome

  • Some studies have shown that prebiotics affect the composition of the microbiota in predictable manner: for example, it has been shown that supplementation with inulin results increased abundance of Bifidobacterium and Faecalibacterium in a cohort of obese women[8], as well as Lactobacillus and Bifidobacterium in rats[9]

  • Against this controlled dietary background, we investigated the effect of individual micronutrient spike-ins, including several prebiotic supplements, to identify the microbial responders and assess the extent to which prebiotics result in predictable compositional changes in the human microbiome

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Summary

Introduction

A quantitative understanding of the forces that shape the composition of the microbiota in vivo is a prerequisite to rationally engineering or manipulating it toward a favorable clinical outcome. Studies aimed at understanding how the microbiome will respond to a targeted change in a specific micronutrient remain logistically daunting To overcome these challenges, we conducted a highly controlled feeding study and dietary perturbation experiment in a healthy human cohort, in which participants were placed on a standardized liquid nutritional meal-replacement for six days. We conducted a highly controlled feeding study and dietary perturbation experiment in a healthy human cohort, in which participants were placed on a standardized liquid nutritional meal-replacement for six days Against this controlled dietary background, we investigated the effect of individual micronutrient spike-ins, including several prebiotic supplements, to identify the microbial responders and assess the extent to which prebiotics result in predictable compositional changes in the human microbiome

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