Next generation probiotics as live biotherapeutics for oro-gastroinestinal infections

Oro-gastrointestinal (OG) infections have been gaining a high interest among the scientific community due to their link to diarrhoeal disease, recognized as one of the major causesof morbidity and mortality worldwide [1-3]. The diarrhoeal treatment often involves antibiotics whose excessive use has been related to the emergence of multidrug-resistantbacteria [2,3]. To overcome this, probiotics have been proposed as a valuable alternative strategy [4]. In the last years, some non-conventional intestinal bacterial species includingFaecalibacterium prausnitzii (Fp), Akkermansia muciniphila (Am) and Anaerobutyricum hallii (Ah) have emerged as next-generation probiotics (NGP), given their demonstratedrelevant bioactivities in prevention and treatment of several metabolic and inflammatory diseases [5=T1–7=T3]. More recently, studies have also revealed their impact on diarrhoeaalleviation [8,9]. Nevertheless, the extent to how these commensal intestinal bacteria will be an effective strategy to treat OG infections remains largely unexplored [10,11]. A majorreason for this handicap is related to their handling difficulties because of their high oxygen sensitivity [6=T2,7=T3]. Given the strong and urgent need for an efficient strategy totreat OG infections, hazardous for populations, in particular children and the elderly [1-3], and given the potential capacity of NGP candidates to avert pathogenic colonization [11],the team has identified a pressing need for investigating NGP strains as a live biotherapeutic strategy to treat and prevent OG infections. To explore such therapeutic potential, thefollowing hypotheses will be put to the test: i) Are NGP strains (FP, Am and Ah) able to inhibit in vitro OG pathogens?; ii) May tailored delivery system(s) for candidate NGP strainsbe developed, via encapsulation, with high resistance at ambient air and stability to in vitro gastrointestinal tract (GIT) passage?; iii) Do developed NGP delivery systems keep theirdesired antimicrobial efficacy in an in vitro faecal model? Conjugating the several areas of team expertise, PROBIOCARE project will develop novel delivery systems tailored to NGP strains with potential in treatment/prevention of OGinfections. To achieve this, a three-fold approach will be developed: 1) assess in vitro inhibitory effect of NGP strains against OG pathogens; strains will be screened for desiredantimicrobial efficacy and adhesion to gut epithelium (Task 1); 2) develop a tailor-made delivery system using encapsulation technology with incorporation of antioxidants andprebiotics which will ensure oxygen tolerance and GIT passage resistance contributing to NGP strain stability and viability in sufficient numbers and potentially enhance their desiredantimicrobial efficacy (Task 2); 3) evaluate the desired antimicrobial efficacy of developed NGP delivery systems in a real environment model system using a faecal model inoculatedwith target pathogen (Task 3). PROBIOCARE project will thus deliver an innovative healthcare disruptive solution capable of being explored within industrial settings given its stabilityand biological efficacy. Notably, PROBIOCARE project contributes to the discovery and development of effective novel preventive and therapeutic strategies with special focus on OGinfections. The fact that we are currently facing new universal health challenges, warrants such targeted interventions, as those presented in PROBIOCARE, which will support people´s health for longer, and help minimize the precariousness of the health and care systems. Such project goals are totally aligned and with high impact on Goal 3 of 2030 Agenda,i.e., “Ensure healthy lives and promote well-being for all at all ages”. Simultaneously, the innovative strategy proposed in PROBIOCARE project to search for solutions againstdiarrhoea-related infections, a main cause of mortality and morbidity affecting more severely developing countries, will contribute to goal 10 of 2030 Agenda, i.e., “Reduce inequalitywithin and among countries”. PROBIOCARE project will be developed through an interdisciplinary/interinstitutional approach (UCP/CESPU) with researchers from vital scientific fields, including microbiology andbiotechnology, and will allow team to increase knowledge and know-how on NGP strains and new technological solutions important for the health sector. PROBIOCARE project willalso play an important role in training Portuguese young scientists involving recent innovations and enable their exchange between laboratories for short-term training. Additionally,this project will be extremely important for the economic competitiveness of Portuguese and European industries (BialactissupportLetter.pdf). This project concept forms the basis ofthe successful application of PI to the 2017 Individual Call to Scientific Employment Stimulus (CEECIND/00520/2017).