Mouse Microbiota Models: Comparing Germ-Free Mice and Antibiotics Treatment as Tools for Modifying Gut Bacteria

As the intestinal microbiota has become better appreciated as necessary for maintenance of physiologic homeostasis and also as a modulator of disease processes, there has been a corresponding increase in manipulation of the microbiota in mouse models. While germ-free mouse models are generally considered to be the gold standard for studies of the microbiota, many investigators turn to antibiotics treatment models as a rapid, inexpensive, and accessible alternative. Here we describe and compare these two approaches, detailing advantages and disadvantages to both. Further, we detail what is known about the effects of antibiotics treatment on cell populations, cytokines, and organs, and clarify how this compares to germ-free models. Finally, we briefly describe recent findings regarding microbiota regulation of infectious diseases and other immunologic challenges by the microbiota, and highlight important future directions and considerations for the use of antibiotics treatment in manipulation of the microbiota

The human gut virome: composition, colonization, interactions, and impacts on human health

The gut virome is an incredibly complex part of the gut ecosystem. Gut viruses play a role in many disease states, but it is unknown to what extent the gut virome impacts everyday human health. New experimental and bioinformatic approaches are required to address this knowledge gap. Gut virome colonization begins at birth and is considered unique and stable in adulthood. The stable virome is highly specific to each individual and is modulated by varying factors such as age, diet, disease state, and use of antibiotics. The gut virome primarily comprises bacteriophages, predominantly order Crassvirales, also referred to as crAss-like phages, in industrialized populations and other Caudoviricetes (formerly Caudovirales). The stability of the virome’s regular constituents is disrupted by disease. Transferring the fecal microbiome, including its viruses, from a healthy individual can restore the functionality of the gut. It can alleviate symptoms of chronic illnesses such as colitis caused by Clostridiodes difficile. Investigation of the virome is a relatively novel field, with new genetic sequences being published at an increasing rate. A large percentage of unknown sequences, termed ‘viral dark matter’, is one of the significant challenges facing virologists and bioinformaticians. To address this challenge, strategies include mining publicly available viral datasets, untargeted metagenomic approaches, and utilizing cutting-edge bioinformatic tools to quantify and classify viral species. Here, we review the literature surrounding the gut virome, its establishment, its impact on human health, the methods used to investigate it, and the viral dark matter veiling our understanding of the gut virome

Dynamics of the human gut phageome during antibiotic treatment

Bacterial viruses contribute to the dynamics of the microbiome communities, as they are involved in the horizontal gene transfer. Previously we studied changes in the gut microbiome of the two healthy individuals over the course of a 6-days antibiotics treatment and subsequent 28 days recovery time (Willmann et al., 2015). Now, from the same samples, the virus-like particles were isolated and sequenced. As the phage sequences are currently poorly represented in reference databases, the reads had to be assembled, annotated and their abundance had to be evaluated via reads mapping. We analyzed and compared patterns of changes in abundance of the phage scaffolds and scaffolds with antibiotics resistant genes, in both phage and whole-genome metagenomic sets. We observed an increase in abundance of scaffolds carrying antibiotic-resistant genes in response to the treatment