Cranberry extracts promote growth of Bacteroidaceae and decrease abundance of Enterobacteriaceae in a human gut simulator model

Abstract

The opportunistic pathogen Escherichia coli, a common member of the human gut microbiota belonging to the Enterobacteriaceae family, is the causative agent of the majority of urinary tract infections (UTIs). The gut microbiota serves as a reservoir for uropathogenic E. coli where they are shed in feces, colonize the periurethral area, and infect the urinary tract. Currently, front line treatment for UTIs consists of oral antibiotics, but the rise of antibiotic resistance is leading to higher rates of recurrence, and antibiotics cause collateral damage to other members of the gut microbiota. It is commonly believed that incorporation of the American cranberry, Vaccinium macrocarpon, into the diet is useful for reducing recurrence of UTIs. We hypothesized such a benefit might be explained by a prebiotic or antimicrobial effect on the gut microbiota. As such, we tested cranberry extracts and whole cranberry powder on a human gut microbiome-derived community in a gut simulator and found that cranberry components broadly modulate the microbiota by reducing the abundance of Enterobacteriaceae and increasing the abundance of Bacteroidaceae. To identify the specific compounds responsible for this, we tested a panel of compounds isolated from cranberries for activity against E. coli, and found that salicylate exhibited antimicrobial activity against both laboratory E. coli and human UTI E. coli isolates. In a gut simulator, salicylate reduced levels of Enterobacteriaceae and elevated Bacteroidaceae in a dose dependent manner.

Oligosaccharides and Complex Carbohydrates: A New Paradigm for Cranberry Bioactivity

“…The use of multiple fraction names to describe essentially the same material has already led to some confusion regarding which cranberry materials and subfractions can be appropriately compared for even the relatively few studies investigating cranberry oligosaccharides to date [25][26][27][28][29]72,[112][113][114][115][131][132][133]. Insufficient material descriptions are also a problem as a minimal standardized method for characterizing and describing oligosaccharide fractions has yet to be established (see Table. Original, author-assigned fraction names have been used when possible but some (italics) have been elaborated upon or added to by the current authors to facilitate discussion.…”

“…O'Connor et al [132] used cranberry materials generated from a mixture of freshly harvested cranberry cultivars. They stated that "whole cranberry powder was prepared by grinding cranberries frozen in liquid nitrogen into a powder" but did not provide relative mass quantities or recoveries for any of their described separation steps.…”

“…From this WBP material they generated "phenolic-enriched cranberry extract," and "phenolic-deficient cranberry extract" using methods that appeared similar to those reported previously [112], although relevant references were not cited. The material the authors [132] describe as "phenolic-deficient" can also be described as oligosaccharide-enriched, though the authors did not use this phrasing. They also reported the inclusion of seven different oligosaccharide fractions for testing in an antimicrobial assay but few details were provided regarding the relative composition of these fractions or the specific methods by which they were prepared [132].…”

“…The material the authors [132] describe as "phenolic-deficient" can also be described as oligosaccharide-enriched, though the authors did not use this phrasing. They also reported the inclusion of seven different oligosaccharide fractions for testing in an antimicrobial assay but few details were provided regarding the relative composition of these fractions or the specific methods by which they were prepared [132]. The materials were described as "crude" and "refined" and as "oligosaccharide" but no indication was given as to relative purity or monomeric composition [132].…”

“…They also reported the inclusion of seven different oligosaccharide fractions for testing in an antimicrobial assay but few details were provided regarding the relative composition of these fractions or the specific methods by which they were prepared [132]. The materials were described as "crude" and "refined" and as "oligosaccharide" but no indication was given as to relative purity or monomeric composition [132]. The crude and refined fractions were reported to have been obtained from "cranberry juice powder" and "cranberry concentrate" while the "oligosaccharide" materials were described as being derived from "cranberry extract," "cranberry concentrate," and "cranberry pomace/ground pomace."…”