Impacts of Domestication and Veterinary Treatment on Mobile Genetic Elements and Resistance Genes in Equine Fecal Bacteria.

Antimicrobial resistance in bacteria is a threat to both human and animal health. We aimed to understand the impact of domestication and antimicrobial treatment on the types and numbers of resistant bacteria, antibiotic resistance genes (ARGs), and class 1 integrons (C1I) in the equine gut microbiome. Antibiotic-resistant fecal bacteria were isolated from wild horses, healthy farm horses, and horses undergoing veterinary treatment, and isolates (9,083 colonies) were screened by PCR for C1I; these were found at frequencies of 9.8% (vet horses), 0.31% (farm horses), and 0.05% (wild horses). A collection of 71 unique C1I+ isolates (17 Actinobacteria and 54 Proteobacteria) was subjected to resistance profiling and genome sequencing. Farm horses yielded mostly C1I+ Actinobacteria (Rhodococcus, Micrococcus, Microbacterium, Arthrobacter, Glutamicibacter, Kocuria), while vet horses primarily yielded C1I+ Proteobacteria (Escherichia, Klebsiella, Enterobacter, Pantoea, Acinetobacter, Leclercia, Ochrobactrum); the vet isolates had more extensive resistance and stronger PC promoters in the C1Is. All integrons in Actinobacteria were flanked by copies of IS6100, except in Micrococcus, where a novel IS5 family element (ISMcte1) was implicated in mobilization. In the Proteobacteria, C1Is were predominantly associated with IS26 and also IS1, Tn21, Tn1721, Tn512, and a putative formaldehyde-resistance transposon (Tn7489). Several large C1I-containing plasmid contigs were retrieved; two of these (plasmid types Y and F) also had extensive sets of metal resistance genes, including a novel copper-resistance transposon (Tn7519). Both veterinary treatment and domestication increase the frequency of C1Is in equine gut microflora, and each of these anthropogenic factors selects for a distinct group of integron-containing bacteria. IMPORTANCE There is increasing acknowledgment that a "one health" approach is required to tackle the growing problem of antimicrobial resistance. This requires that the issue is examined from not only the perspective of human medicine but also includes consideration of the roles of antimicrobials in veterinary medicine and agriculture and recognizes the importance of other ecological compartments in the dissemination of ARGs and mobile genetic elements such as C1I. We have shown that domestication and veterinary treatment increase the frequency of occurrence of C1Is in the equine gut microflora and that, in healthy farm horses, the C1I are unexpectedly found in Actinobacteria, while in horses receiving antimicrobial veterinary treatments, a taxonomic shift occurs, and the more typical integron-containing Proteobacteria are found. We identified several new mobile genetic elements (plasmids, insertion sequences [IS], and transposons) on genomic contigs from the integron-containing equine bacteria.

Fecal Microbiota Transplantation: Expanding Horizons for Clostridium difficile Infections and Beyond.

Fecal Microbiota Transplantation (FMT) methodology has been progressively refined over the past several years. The procedure has an extensive track record of success curing Clostridium difficile infection (CDI) with remarkably few adverse effects. It achieves similar levels of success whether the CDI occurs in the young or elderly, previously normal or profoundly ill patients, or those with CDI in Inflammatory Bowel Disease (IBD). While using FMT to treat CDI, however, we learned that using the procedure in other gastrointestinal (GI) diseases, such as IBD without CDI, generally fails to effect cure. To improve results in treating other non-CDI diseases, innovatively designed Randomized Controlled Trials (RCTs) will be required to address questions about mechanisms operating within particular diseases. Availability of orally deliverable FMT products, such as capsules containing lyophilised fecal microbiota, will simplify CDI treatment and open the door to convenient, prolonged FMT delivery to the GI tract and will likely deliver improved results in both CDI and non-CDI diseases.

Fecal microbiota transplantation in gastrointestinal diseases: what practicing physicians should know.

Clostridium difficile infection (CDI) is one of the most commonly reported nosocomial pathogens in the United States and Europe, with recent CDI-associated mortality in the United States approaching 30 000 deaths annually. Antibiotics remain the preferred treatment for CDI; however, a minority of patients experience numerous relapses and are treated with restoration of the bowel microbiota, termed fecal microbiota transplantation (FMT). FMT involves the introduction of a fecal suspension from a healthy donor into the gut of the infected patient to cure the CDI and replace depleted components of the gut microbiota. FMT is particularly effective and safe in curing CDI, using a colonoscope or enema to deliver 1 to 2 infusions. Given that 6425 CDIs were reported in Poland in 2014, practicing physicians should understand the benefits and limitations of FMT in CDI as this novel therapy has rapidly advanced to the level of the "standard-of-care" status in Australia, the United States, and many parts of Europe. FMT has been administered either as a suspension in saline, a highly refined liquid product which can be frozen, as lyophilized powder in capsules, and as an encapsulated spore preparation. The ultimate products to reach the market will be shaped by the indications approved by regulatory bodies. At present, the fecal suspension in saline remains the treatment of choice to terminate relapsing and severe CDI, which we will review here. The use of FMT for non-CDI indications, such as inflammatory bowel disease and irritable bowel syndrome, is likely to increase. At present, these indications remain in the domain of research institutions.