Title: Antiinfectives and microbiota in era of antimicrobial resistance

Biography:

Ivana Haluskova Balter is a french medical professional specialized in infectious diseases, internal medicine, certified in immunology and pediatrics, MBA vaccinology and years of clinical practice. She is also certified in health and diplomacy with live multi-country medical field experience in Southeast Asia (India in particular), West/Central/East Europe. She has over 17 years of experience in senior medical lead positions in pharmaceutical research. She is a member of World alliance against antibiotic resistance and French immunology society (SFI) administrative boards and several international academic societies with focus at the innovation of R&D, reflecting immunology and genetic variability, the role of immunologic approach for treatment and diagnostic to tackle the problem of resistance and the role of microbiota to empower host immune response with extensive clinical application. She is also the member of the international advisory group (CHD India) in order to attract attention to the crucial importance of health issues for sustainable economic development and security.

Abstract

Bacteria, viruses, parasites and fungi that are resistant to drug cause 700,000 death each year. By 2050 superbugs inured to treatments could cause up to 10 million deaths annually and costs the global economy US$100 trillion. AMR resistance is regarded nowadays as a major threat to global public health. The issue is receiving high-level political attention (G7 and G20 in 2017 for first time). The list was drawn up in a bid to guide and promote research and development (R&D) of new antibiotics, as part of WHO’s efforts  for AMR (27th Feb 2017). Antibiotics shape the ecology of the gut microbiota in profound ways, causing lasting changes to developing and mature microbiotas. The application of next-generation sequencing has enabled detailed views of the side effects these drugs have on commensal populations during treatment of infections. The gut microbiota is relatively stable in healthy adults but the composition of the gut microbiota can change rapidly due to various reasons - nutrition related factors, birth mode, use of antibiotics etc. In animal models, treatment with antibiotics revealed behavioural differences and reduced intestinal permeability.  Preclinical findings indicated that antibiotic treatment impact metabolic function as observed in other studies studying microbiota functions. High throughput sequencing reveals the incomplete, short term recovery of infant gut microbiota following parenteral antibiotic treatment with ampicillin and gentamicin. Pediatric dose of penicilin in a mice model, showed significant effects  in terms of social behaviour, social interaction, social avoidance. Experimental mice that were given the probiotic bacteria Lactobacillus rhamnosus  JB-1 in addition to the antibiotics showed fewer of the changes in brain biology and behaviour. The experiment showed not only that changes in gut microbiota could affect the brain, but also that the specific type of bacteria mattered for the end result. Antibiotic use is associated with alteration of the gut microbiome and metabolic activity. Investigations were done in order to study the association between infant antibiotic exposure (aged < 24 months) and childhood obesity or overweight. Antibiotic exposure in infants, aged < 24 months, was associated with a small increase in odds of childhood overweight or obesity in some subgroups of children.  It is known that he first 3 years of life (also termed a ‘window of opportunity’) may represent the most critical period for dietary interventions aimed at gut microbiota modulation for improving child growth and development. In this context, disruption of early-life interactions between host and gut microbiota could have lasting effects by affecting host immunological and metabolic development. A recent study has found that early-life antibiotic exposure in non-obese diabetic mice may accelerate T1D development. Advances in clinical research and development in area of anti-infectives coupled with a renewed interest in the use of probiotics, FMTs (fecal microbiota transplantation) and phage therapy along with thoughtful development of vaccines and monoclonal antibodies represents multiple paths in approach to tackle AMR considering preservation of microbiota.  New medications that protects the gut microbiota (and gut dysbiosis) and preserve antibiotic efficacy are under clinical development. Despite the initial existing preclinical findings, scepticism is warranted when extrapolating findings to human physiology and disease. There is currently limited evidence from epidemiological or high-quality clinical studies to show major effects of the normal gut microbiota or microbiota modulation with dietary changes, prebiotics, probiotics, or antibiotics on gut-brain interactions or on brain function (i.e., affect, cognition) in healthy adult humans or in human disease. From long-term perspective, the research could have serious implications for those living with mental or behavioural problems. In the context of raising antimicrobial resistance, the World Health Organisation has launched the Global Antimicrobial Resistance Surveillance System (GLASS) initiative in order to strengthen bacteriology laboratories in low-and middle income countries for targeted antibiotic resistance surveillance and this might be occasion to gather better understanding and  necessary information. In conclusion, there is a need for extended clinical research triggered by burning issue of anti-infective resistance and  surveillance studies monitoring antibiotic resistance which include infants (early in life microbiota alteration ) would bring useful additional insights. It is an occasion to gather more information on the microbiota’s effects, role of immune and neuroendocrine system and to help in understanding and preventing gut microbiota mediated pathologies in humans and the most appropriate interventions and tools to be used.