About this Research Topic
The introduction of next generation sequencing techniques has boosted the research of human microbiota. The importance of composition of microbiota has been established. The perturbation of its composition can lead to imbalance and dysbiosis – a disease characterized by the changes in microbiota. The latter has been demonstrated in inflammatory bowel disease, irritable bowel syndrome, allergy, obesity, colon cancer and even autism. The ability to restore the balance with microbial intervention was also demonstrated. The stunning example is fecal transplant for the treatment of recurrent Clostridium difficile infection.
The knowledge of balanced microbiota, microbial physiology and human pathophysiology can lead to selection of new microbial strains and mixtures, or targeted improvement of existing microbial strains, achieved by mutagenesis, genetic engineering and synthetic biology. The new species will exceed the existent probiotic definition and food applications, but may well be adopted by the pharmaceutical industry as “pharmabiotics” or “live biotherapeutic products”.
The use of microbes in therapy would primarily focus on safe microbes that are used in food, such as lactic acid bacteria, baker’s yeast and commensal bacteria, such as E. coli, particularly due to extensive knowledge of their physiology, genomics and well established tools for genetic modification and synthetic biology. However, emerging members of microbiota with defined beneficial effects, such as Faecalibacterium prausnitzii, are expected to make important impact. Also, pathogenic bacteria can be exploited for therapy, as it was already demonstrated by Salmonella thyphimurium for the treatment of cancer.
The therapeutic microbes can be applied in human and veterinary medicine. Possible indications include vaccination, immunomodulation, inflammation, cancer, infectious diseases and metabolic disorders. Microbes can be administered to gastrointestinal tract (orally) or to other mucosal surfaces (intranasally, intrapulmonary). Vaginal microbiota could be an attractive target due to the predominance of well-studied Lactobacillus genus. The importance of skin microbiota is also well established.
The microbes can be used as delivery vehicles for therapeutic proteins (e. g. anti-inflammatory cytokines), DNA for gene therapy, antigens for vaccination, microbial metabolites, anti-microbials, vitamins, or enzymes for activation of prodrugs. Engineering of microbes can be associated with advanced tools of synthetic biology.
These can include genetic circuits that sense and respond to specific environmental conditions, or that release drugs in synchronized cycles.
The therapeutic use of microbes has bright future, as can be deduced from exciting findings of microbiota studies that are reported daily, as well as numerous successful proof-of-principle reports from animal models. The overall advancement of the challenging field is the main goal of this Research Topic.
The use of microbes and recombinant microbes in therapy goes hand in hand with regulatory requirements and containment strategies. Tackling these issues represents a final step toward their clinical application.
Keywords: genetic engineering, bacteria, probiotics, protein delivery, therapy
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