Phage study: effects of supplemental bacteriophage intake on inflammation and gut microbiota in healthy adults

Authors: FEBVRE, HALLIE - Colorado State University; RAO, SANGEETA - Colorado State University; GINDIN, MELINDA - Colorado State University; GOODWIN, NATALIE - Colorado State University; FINER, ELIJAH - Colorado State University; VIVANCO, JORGE - Colorado State University; LU, SHEN - Colorado State University; Manter, Daniel; WALLACE, TAYLOR - George Mason University; WEIR, TIFFANY - Colorado State University

Submitted to: Nutrients
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/14/2019
Publication Date: 3/20/2019
Citation: Febvre, H., Rao, S., Gindin, M., Goodwin, N., Finer, E., Vivanco, J., Lu, S., Manter, D.K., Wallace, T., Weir, T. 2019. Phage study: effects of supplemental bacteriophage intake on inflammation and gut microbiota in healthy adults. Nutrients. 11(3):666. https://doi.org/10.3390/nu11030666.
DOI: https://doi.org/10.3390/nu11030666

Interpretive Summary: Intestinal health and the gut microbiota have increasingly been linked to various chronic health outcomes. Imbalances in the gut microbiota resulting from poor diet, stress, antibiotic use, and other lifestyle and environmental factors are associated with the development of intestinal inflammation and bowel irregularities. As a result, there is a growing interest in identifying dietary supplements that favorably modulate gut microbial populations. Bacteriophages (or phages) are among the candidates being explored as potential microbial modifiers in promoting intestinal health. These ubiquitous, bacteria-targeting viruses exhibit a high degree of host specificity, suggesting utility for selectively reducing pathogenic or pro-inflammatory bacteria. The objective of the current study was to determine how daily consumption of supplemental Escherichia coli-targeting phages influences the gut microbiota of healthy adults with self-reported gastrointestinal distress.Here, we report that 28 days of phage consumption did not substantially alter the global gut microbiota profiles of most individuals, but did reduce populations of the target bacteria, E. coli, as well as modify a number of individual bacterial species, including an increase in amplicon sequence variants (ASVs) mapping to Eubacterium spp., which is one of the most abundant genera in the healthy human gut. These data highlight the potential of bacteriophages for selective modification of targeted microbial species of the human gut microbiome.

Technical Abstract: The gut microbiota is increasingly recognized as an important modulator of human health. As such, there is a growing need to identify effective means of selectively modifying gut microbial communities. Bacteriophages, which were briefly utilized as clinical antimicrobials in the early 20th century, present an opportunity to selectively reduce populations of undesirable microorganisms. However, whether intentional consumption of specific bacteriophages affects overall gut ecology is not yet known. Using a commercial cocktail of Escherichia coli-targeting bacteriophages, we examined their effects on gut microbiota and markers of intestinal and systemic inflammation in a healthy human population. In a double-blinded, placebo-controlled crossover trial, normal to overweight adults consumed bacteriophages for 28 days. Stool and blood samples were collected and used to examine inflammatory markers, lipid metabolism, and gut microbiota. Reductions in fecal E. coli loads were observed with phage consumption. However, there were no significant changes to alpha and beta diversity parameters, suggesting that consumed phages did not globally disrupt the microbiota. However, specific populations were altered in response to treatment, including increases in members of the butyrate-producing genera Eubacterium and a decreased proportion of taxa most closely related to Clostridium perfringens. Short-chain fatty acid production, inflammatory markers, and lipid metabolism were largely unaltered, but there was a small but significant decrease in circulating interleukin-4 (Il-4). Together, these data demonstrate the potential of bacteriophages to selectively reduce target organisms without global disruption of the gut community.