Examining the Effects of an Anti-Salmonella Bacteriophage Preparation, BAFASAL®, on Ex-Vivo Human Gut Microbiome Composition and Function Using a Multi-Omics Approach.

Janice Mayne,Alain Stintzi,Zhibin Ning,Ewelina Wójcik,Daniel Figeys,James Butcher,Xu Zhang,Krystal Walker,Jarosław Dastych

doi:10.3390/v13091734

Abstract

Salmonella infections (salmonellosis) pose serious health risks to humans, usually via food-chain contamination. This foodborne pathogen causes major food losses and human illnesses, with significant economic impacts. Overuse of antibiotics in the food industry has led to multidrug-resistant strains of bacteria, and governments are now restricting their use, leading the food industry to search for alternatives to secure food chains. Bacteriophages, viruses that infect and kill bacteria, are currently being investigated and used as replacement treatments and prophylactics due to their specificity and efficacy. They are generally regarded as safe alternatives to antibiotics, as they are natural components of the ecosystem. However, when specifically used in the industry, they can also make their way into humans through our food chain or exposure, as is the case for antibiotics. In particular, agricultural workers could be repeatedly exposed to bacteriophages supplemented to animal feeds. To our knowledge, no studies have investigated the effects of such exposure to bacteriophages on the human gut microbiome. In this study, we used a novel in-vitro assay called RapidAIM to investigate the effect of a bacteriophage mixture, BAFASAL®, used in poultry farming on five individual human gut microbiomes. Multi-omics analyses, including 16S rRNA gene sequencing and metaproteomic, revealed that ex-vivo human gut microbiota composition and function were unaffected by BAFASAL® treatment, providing an additional measure for its safety. Due to the critical role of the gut microbiome in human health and the known role of bacteriophages in regulation of microbiome composition and function, we suggest assaying the impact of bacteriophage-cocktails on the human gut microbiome as a part of their safety assessment.

Highlights

As the world population increases, so does food demand
Following 18 h culturing, the bacterial cells were pelleted, DNA extracted for metagenomic analyses using 16S rRNA gene-based sequencing, and proteins extracted and digested for metaproteomic analysis, as described in materials and methods
This study aimed to examine the effects of the BAFASAL® agricultural bacteriophage mixture on human gut microbiome function and composition using an in-vitro RapidAIM platform

Summary

Introduction

As the world population increases, so does food demand. Plant and animal diseases can seriously impact food supplies and food safety, resulting in food shortages and causing significant economic impacts. Most zoonotic diseases have been treated with antibiotics, with 73% of all antibiotics in the world used in animal production [3]. The rise of multidrug-resistant bacteria has become such a global concern that by 2022, the European Union (EU) will ban the prophylactic use of clinically relevant antibiotics in food production, with the exemption of veterinary prescriptions [6], and other countries are following suit. Without such interventions, antimicrobial resistance (AMR) will result in an estimated 10 million deaths by 2050 [5]

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