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

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.

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Examining the effects of an anti-Salmonella bacteriophage preparation, BAFASAL, on ex vivo human gut microbiome composition and function using a multi-omics approach

10.1101/2021.07.04.451072 ◽

2021 ◽

Author(s):

Janice Mayne ◽

Xu Zhang ◽

James Butcher ◽

Krystal Walker ◽

Zhibin Ning ◽

...

Keyword(s):

Food Chain ◽

Gut Microbiome ◽

Ex Vivo ◽

Human Gut ◽

Microbiome Composition ◽

Human Gut Microbiome ◽

Salmonella Infections ◽

And Function ◽

The Impact

Salmonella infections (salmonellosis) pose serious health risks to humans, usually via contamination in our food chain. This foodborne pathogen causes major food losses and human illnesses that result in significant economic impacts. Pathogens such as Salmonella have traditionally been kept at bay through the use of antibiotics, but antibiotic overuse within the food industry has led to the development of numerous multidrug-resistant bacterial strains. Thus, governments are now restricting antibiotic use, forcing the industry to search for alternatives to secure safe 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. One example is BAFASEL, a commercial bacteriophage mixture that specifically targets Salmonella and is currently approved for use in poultry farming. 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 in animal feeds. To the best of 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 BAFASAL's potential impact 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.

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The gut mycobiome: a novel player in chronic liver diseases

Journal of Gastroenterology ◽

10.1007/s00535-020-01740-5 ◽

2020 ◽

Author(s):

Lu Jiang ◽

Peter Stärkel ◽

Jian-Gao Fan ◽

Derrick Eugene Fouts ◽

Petra Bacher ◽

...

Keyword(s):

Human Health ◽

Gut Microbiome ◽

Liver Diseases ◽

Therapeutic Targets ◽

Chronic Liver Diseases ◽

Human Gut ◽

Human Gut Microbiome ◽

The Impact ◽

Potential Use

Abstract The human gut microbiome (bacteria, fungi, viruses, and archaea) is a complex and diverse ecosystem. It plays an important role in human health, but is involved in several intestinal and extraintestinal diseases. Most research to date has focused on the role of bacteria, while studies focusing on fungi (also referred to as “mycobiome” or “fungome”) are still in its infancy. In this review, we focus on the existing literature available about the gut mycobiome with an emphasis on compositional mycobiome changes associated with liver diseases, the impact on pathogenesis of disease, and its potential use as therapeutic targets. We also provide insights into current methodologies of studying mycobiome, and we highlight the interkingdom interactions in the context of disease and how they affect health of the host. Herein, by focusing on the gut mycobiome, this review provides novel insights and directions for liver research.

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Acquired interbacterial defense systems protect against interspecies antagonism in the human gut microbiome

10.1101/471110 ◽

2018 ◽

Cited By ~ 1

Author(s):

Benjamin D. Ross ◽

Adrian J. Verster ◽

Matthew C. Radey ◽

Danica T. Schmidtke ◽

Christopher E. Pope ◽

...

Keyword(s):

Gut Microbiome ◽

Gene Clusters ◽

Protective Capacity ◽

Human Gut ◽

Microbiome Composition ◽

Toxin Resistance ◽

Human Gut Microbiome ◽

Bacterial Antagonism ◽

The Impact

AbstractThe impact of direct interactions between co-resident microbes on microbiome composition is not well understood. Here we report the occurrence of acquired interbacterial defense (AID) gene clusters in bacterial residents of the human gut microbiome. These clusters encode arrays of immunity genes that protect against type VI secretion toxin-mediated intra- and inter-species bacterial antagonism. Moreover, the clusters reside on mobile elements and we demonstrate that their transfer is sufficient to confer toxin resistance in vitro and in gnotobiotic mice. Finally, we identify and validate the protective capacity of a recombinase-associated AID subtype (rAID-1) present broadly in Bacteroidales genomes. These rAID-1 gene clusters have a structure suggestive of active gene acquisition and include predicted immunity factors of toxins deriving from diverse organisms. Our data suggest that neutralization of contact-dependent interbacterial antagonism via AID systems shapes human gut microbiome ecology.

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Comprehensive assessment of functional effects of commonly used sweeteners on ex vivo human gut microbiome

10.1101/2022.01.15.474735 ◽

2022 ◽

Author(s):

Zhongzhi Sun ◽

Wenju Wang ◽

Leyuan Li ◽

Xu Zhang ◽

Zhibin Ning ◽

...

Keyword(s):

Gut Microbiome ◽

Comprehensive Evaluation ◽

Ex Vivo ◽

Food Additives ◽

Functional Responses ◽

Sugar Alcohols ◽

Human Gut ◽

Functional Changes ◽

Microbiome Composition ◽

Human Gut Microbiome

The gut microbiome composition and function are associated with health and diseases. Sweeten-ers are widely used food additives, although many studies using animal models have linked sweetener consumption to gut microbial changes and health issues. Whether sweeteners directly change the human gut microbiome functionality remains largely unknown. In this study, we sys-tematically investigated the responses of five human gut microbiomes to 21 common sweeteners, using an approach combining high-throughput ex vivo microbiome culturing and metaproteomics to quantify functional changes in different taxa. Hierarchical clustering based on metaproteomic responses of individual microbiomes resulted in two clusters. The first cluster was composed of non-caloric artificial sweeteners (NAS) and two sugar alcohols with shorter carbon backbones (4-5 carbon atoms), and the second cluster was composed of sugar alcohols with longer carbon backbones. The metaproteomic functional responses of the second cluster were similar to the prebiotic fructooligosaccharides and kestose, indicating that these sugar alcohol-type sweeteners have potential prebiotic functions. This study provides a comprehensive evaluation of the direct effects of commonly used sweeteners on the functions of the human gut microbiome using a func-tional metaproteomics approach, improving our understanding of the roles of sweeteners on mi-crobiome-associated human health and disease issues.

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Taxonomic signatures of cause-specific mortality risk in human gut microbiome

Nature Communications ◽

10.1038/s41467-021-22962-y ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Aaro Salosensaari ◽

Ville Laitinen ◽

Aki S. Havulinna ◽

Guillaume Meric ◽

Susan Cheng ◽

...

Keyword(s):

Mortality Risk ◽

Gut Microbiome ◽

Human Gut ◽

Cross Sectional ◽

Microbiome Composition ◽

Human Gut Microbiome ◽

Non Invasive ◽

Sequencing Technologies

AbstractThe collection of fecal material and developments in sequencing technologies have enabled standardised and non-invasive gut microbiome profiling. Microbiome composition from several large cohorts have been cross-sectionally linked to various lifestyle factors and diseases. In spite of these advances, prospective associations between microbiome composition and health have remained uncharacterised due to the lack of sufficiently large and representative population cohorts with comprehensive follow-up data. Here, we analyse the long-term association between gut microbiome variation and mortality in a well-phenotyped and representative population cohort from Finland (n = 7211). We report robust taxonomic and functional microbiome signatures related to the Enterobacteriaceae family that are associated with mortality risk during a 15-year follow-up. Our results extend previous cross-sectional studies, and help to establish the basis for examining long-term associations between human gut microbiome composition, incident outcomes, and general health status.

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Role of dietary fiber in the recovery of the human gut microbiome and its metabolome

Cell Host & Microbe ◽

10.1016/j.chom.2020.12.012 ◽

2021 ◽

Author(s):

Ceylan Tanes ◽

Kyle Bittinger ◽

Yuan Gao ◽

Elliot S. Friedman ◽

Lisa Nessel ◽

...

Keyword(s):

Dietary Fiber ◽

Gut Microbiome ◽

Human Gut ◽

Human Gut Microbiome

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Global and temporal state of the human gut microbiome in health and disease

10.21203/rs.3.rs-339282/v1 ◽

2021 ◽

Author(s):

Saeed Shoaie ◽

Sunjae Lee ◽

Mathieu Almeida ◽

Gholamreza Bidkhori ◽

Nicolas Pons ◽

...

Keyword(s):

Gut Microbiome ◽

Integrative Analysis ◽

Human Gut ◽

Human Gut Microbiome ◽

Health And Disease ◽

One Year ◽

The Stability ◽

Clinical Phenotyping ◽

Sampling Times

Abstract The role of gut microbiota in humans is of great interest, and metagenomics provided the possibilities for extensively analysing bacterial diversity in health and disease. Here we explored the human gut microbiome samples across 19 countries, performing compositional, functional and integrative analysis. To complement these data and analyse the stability of the microbiome, we followed 86 healthy Swedish individuals over one year, with four sampling times and extensive clinical phenotyping. The integrative analysis of temporal microbiome changes shows the existence of two types of species with a tendency to vary in abundance with time, here called outflow and inflow species. Importantly, the former tends to be enriched in disease, while the latter is enriched in health. We suggest that the decrease of disease-associated outflow and the increase of health-associated inflow species with time may be a fundamental albeit previously unrecognized aspect of the homeostasis maintenance in a healthy microbiome.

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Role of Human Gut Microbiome in Health and Disease

Microbiome-Host Interactions ◽

10.1201/9781003037521-9 ◽

2021 ◽

pp. 101-112

Author(s):

Nazar Reehana ◽

Mohamed Yousuff Mohamed Imran ◽

Nooruddin Thajuddin ◽

D. Dhanasekaran

Keyword(s):

Gut Microbiome ◽

Human Gut ◽

Human Gut Microbiome ◽

Health And Disease

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Health and disease markers correlate with gut microbiome composition across thousands of people

Nature Communications ◽

10.1038/s41467-020-18871-1 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 2

Author(s):

Ohad Manor ◽

Chengzhen L. Dai ◽

Sergey A. Kornilov ◽

Brett Smith ◽

Nathan D. Price ◽

...

Keyword(s):

Gut Microbiome ◽

Lifestyle Factors ◽

Clinical Markers ◽

Human Gut ◽

Microbiome Composition ◽

Targeted Interventions ◽

Human Gut Microbiome ◽

Host Diet ◽

Microbe Interactions ◽

Host Microbe Interactions

Abstract Variation in the human gut microbiome can reflect host lifestyle and behaviors and influence disease biomarker levels in the blood. Understanding the relationships between gut microbes and host phenotypes are critical for understanding wellness and disease. Here, we examine associations between the gut microbiota and ~150 host phenotypic features across ~3,400 individuals. We identify major axes of taxonomic variance in the gut and a putative diversity maximum along the Firmicutes-to-Bacteroidetes axis. Our analyses reveal both known and unknown associations between microbiome composition and host clinical markers and lifestyle factors, including host-microbe associations that are composition-specific. These results suggest potential opportunities for targeted interventions that alter the composition of the microbiome to improve host health. By uncovering the interrelationships between host diet and lifestyle factors, clinical blood markers, and the human gut microbiome at the population-scale, our results serve as a roadmap for future studies on host-microbe interactions and interventions.

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