Abstract

Recent data comparing germ-free to conventionally-raised mice demonstrated that energy homeostasis of colonocytes is dependent on gut microbiota through regulation of short chain fatty acids (SCFA) production and glucose utilization. We sought to evaluate 18F-FDG PET-CT as a novel technique for functional imaging of alterations in glucose metabolism as a result of the interaction between the gut microbiota and the human host. We conducted a prospective study in healthy humans that underwent 18F-FDG PET-CT and sampling of the gut microbiota before and after orally administered broad-spectrum antibiotics. The primary outcomes were total and regional physiologic colonic 18F-FDG uptake (measured as the mean and max standardized uptake values [SUVmean and SUVmax]). The study demonstrated significant increases in physiologic colonic 18F-FDG uptake in all study participants following antibiotic treatment and a 4-5log reduction of gut bacterial load. The mean increase in SUVmax was 0.63±0.37 SD (p = 0.004) and the median increase was 0.42 with an IQR of 0.40–0.81. The mean increase in SUVmean was 0.31±0.24 SD (p = 0.01) and the median increase was 0.41 with an IQR of 0.06–0.55. A likely explanation for this phenomenon is a shift in colonocyte metabolism to glycolysis due to a shortage of SCFA.

Highlights

  • The gut microbiota is regarded by many as a distinct organ within the human body with a central role in metabolism, immunity, and inflammation [1]

  • The gut microbiota is required for energy homeostasis in colonocytes, and short chain fatty acids (SCFA), produced by the gut microbiota mainly from the fermentation of undigestible carbohydrates, serve as the main nutrient for colonocytes [16,17,18]

  • Both in mice and humans, that the use of a combined protocol of two antibiotics and Polyethylene glycol (PEG) on the second day reduces both culturable bacteria and 16S gene copy number by approximately 4–5 logs, creating a gut microbial environment that more closely mimics a germ-free mouse [19]

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Summary

Introduction

The gut microbiota is regarded by many as a distinct organ within the human body with a central role in metabolism, immunity, and inflammation [1]. Previous in vitro and in vivo studies [18] demonstrated a shift in colonic metabolism from SCFA to glycolysis in germ-free compared to conventionally-raised mice We recently demonstrated, both in mice and humans, that the use of a combined protocol of two antibiotics (vancomycin and neomycin taken for 3 consecutive days) and Polyethylene glycol (PEG) on the second day reduces both culturable bacteria and 16S gene copy number by approximately 4–5 logs, creating a gut microbial environment that more closely mimics a germ-free mouse [19]

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