Technological advances in studying the human microbiome in depth have enabled the identification of microbial signatures associated with health and disease. This confirms the crucial role of microbiota in maintaining homeostasis and the host health status. Nowadays, there are several ways to modulate the microbiota composition to effectively improve host health; therefore, the development of therapeutic treatments based on the gut microbiota is experiencing rapid growth. In this review, we summarize the influence of the gut microbiota on the development of infectious disease and cancer, which are two of the main targets of microbiome-based therapies currently being developed. We analyze the two-way interaction between the gut microbiota and traditional drugs in order to emphasize the influence of gut microbial composition on drug effectivity and treatment response. We explore the different strategies currently available for modulating this ecosystem to our benefit, ranging from 1st generation intervention strategies to more complex 2nd generation microbiome-based therapies and their regulatory framework. Lastly, we finish with a quick overview of what we believe is the future of these strategies, that is 3rd generation microbiome-based therapies developed with the use of artificial intelligence (AI) algorithms.

Genome mining has proven its usefulness in the search for novel bioactive compounds produced by microorganisms, and halogenases comprise an interesting starting point. In this work, we have identified a new halogenase coding gene that led to the discovery of novel lipopetide nonribosomal peptide synthetase/polyketide synthase (NRPS/PKS)-derived natural products, the colibrimycins, produced by Streptomyces sp. strain CS147, isolated from the Attini ant niche.

Salmonella enterica serovar Rissen is one of the most common serovars found in pigs and pork products in different countries, including Spain. However, information on the molecular bases of antimicrobial drug resistance and the population structure of Salmonella Rissen from different sources in Spain is limited. The present study focused on 84 isolates collected in Spain from pig and beef carcasses, foods and clinical samples associated with sporadic cases of gastroenteritis, and one outbreak. The majority of the isolates were resistant to tetracycline (73.8%), mainly conferred by tet (A). Resistances to streptomycin ( aadA1 -like, aadA2 , and strAB ), sulfonamides ( sul1 , sul2 , and sul3 ), trimethoprim ( dfrA1 -like and dfrA12 ), ampicillin ( bla _TEM-1-like ), and chloramphenicol ( cmlA1 -like) were also detected, with frequencies ranging from 12% to 20.2%. Most of the identified genes were carried by integrons, including three class 1 integrons of the sul1 type, a class 1 integron of the sul3 type, and the class 2 integron of Tn 7 . Two sul1 integrons, the sul3 integron, and the class 2 integron are first reported in Salmonella Rissen. Typing of the isolates with Xba I pulsed-field gel electrophoresis detected a major clone, which was circulating in humans and animals during the past decade, and was responsible for the outbreak. The obtained results are relevant for food safety and public health.

In this study, the incidence and genetic bases of nitrofurantoin resistance were established for clinical isolates of two successful clones of Salmonella enterica serovar Typhimurium, the pandemic “DT 104” and the pUO-StVR2 clone. A total of 61 “DT 104” and 40 pUO-StVR2 isolates recovered from clinical samples during 2008–2014 and assigned to different phage types, were tested for nitrofurantoin susceptibility. As previously shown for older isolates, all newly tested pUO-StVR2 isolates were highly resistant to nitrofurantoin (minimal inhibitory concentration [MIC] of 128 μg/ml), while 42.6%, 24.6%, and 32.8% of the “DT 104” isolates were susceptible, showed intermediate resistance or were highly resistant, with MICs of 8, 64, and 128 μg/ml, respectively. The genetic bases of nitrofurantoin resistance were established by PCR amplification and sequencing of the nfsA and nfsB genes encoding oxygen-insensitive nitroreductases. pUO-StVR2 isolates shared identical alterations in both nfsA (IS 1 inserted into the coding region) and nfsB (in frame duplication of two codons). “DT 104” isolates with intermediate or high resistance had a missense mutation affecting the start codon of nfsA , while a single resistant isolate carried an additional frameshift mutation affecting nfsB . Complementation studies, performed with wild-type nfsA and nfsB , cloned independently and together into low and high copy-number vectors, confirmed NfsA and NfsB as responsible for nitrofurantoin toxicity. The same alterations persisted along time in isolates of each clone belonging to different phage types. Accordingly, changes leading to nitrofurantoin resistance have probably occurred before phage type diversification.

Three unrelated sequence type 131 (ST131), ST58, and ST83 Escherichia coli isolates with low-level resistance to imipenem and resistance to ertapenem were recovered in a Spanish hospital from July to October 2012. They were positive for bla _OXA-48 carried by an IncL/M conjugative plasmid, which may have been acquired from Klebsiella pneumoniae .