Development of low-cost microbiome-based diagnostic tools for respiratory infections may be key to future antimicrobial stewardship
by Dr. Debby Bogaert
In low and middle-income countries (LMICs), major efforts have been devoted to improving the availability of vaccines, antibiotics and standardized treatment protocols, to reduce the incidence of respiratory infections and the resulting fatalities. However, despite these efforts we can still regard pneumonia as the biggest killer of children on a global scale. Meanwhile, due to the chronic overuse of antimicrobials globally, the threat of antibiotic resistance has emerged among common disease-causing bugs. This disproportionally affects LMICs, where the burden of these infections is greatest. Greater efforts are required to understand the exact mechanisms and drivers of disease severity leading to childhood illness, since this could directly help to design new preventive strategies and guide effective antibiotic treatment.
In this context, I would like to highlight the new emerging science of the human microbiome. Trillions of bacteria, fungi, and viruses inhabit the human body, and together provide a multitude of beneficial functions for its host. These are all functions that human cells cannot provide for themselves, such as the digestion of food, keeping potential harmful pathogens at bay, and teaching the immune system what is friend or foe. Unfortunately, many beneficial microbes are highly susceptible to commonly used broad-spectrum antibiotics. As a result, treatment for infectious diseases, such as pneumonia, is not only driving antimicrobial resistance, but also depriving the host of beneficial microbes, with knock on effects on the host’s and microbiome’s defence mechanisms.
This new research field is rapidly unraveling the role of the human microbiome in preventing pneumonia in children. Recent studies have suggested respiratory infections are merely a result of interplay between viruses and bacteria, or even more complex mixed infections, rather than caused by a single organism. They also identified potential beneficial microbes that may protect infants and young children against viral and bacterial acquisition and infection, and may even alter severity of disease. Importantly, those bacteria seem to be universally present, depending on natural resources such as the mothers gut and vaginal microbes, and breastmilk components, while varying less with genetic background and socio-economic status. Although this is promising, we must move further to try to understand exactly what role these microbes play in the protection against infections.
Interestingly, however, since microbiome profiling provides in-depth detail of any types of microbes and their relative abundance at time of infection, it could potentially be used as diagnostic tool as well. Where conventional microbial techniques often fail to identify the causative pathogen, due to lack of specificity and their targeted approach, microbiome profiling could provide the level of detail and certainty required. Using microbiome-based diagnostics, including detection of resistance genes, may thereby improve targeted therapy and reduce blind treatment with broad-spectrum antibiotics.
Real-time sequencing, such as the MinION nanopore sequencing technology (Oxford Nanopore), is the newest platform available for this type of diagnostics. In principle, the technique is fast, simple and does not require sophisticated laboratory equipment allowing for remote testing. Single specimen sequencing, combined with a rapid turnaround time, could affect current practice dramatically, bringing antimicrobial stewardship to a whole new level. Targeted therapy, in combination with microbiome-centered antibiotic stewardship, would also help to avoid damage to the diverse range of beneficial microbes and reduce the risk of short- and long-term health problems related to antimicrobial use. Several institutes in the UK and the USA are already studying the applications of this technique for improved diagnostics and treatment in severe adult community-acquired pneumonia and ventilator-associated pneumonia. However, there are few initiatives visible on the pediatric side of the spectrum, let alone in LMICs. This might be a consequence of several ‘pediatric’ hurdles, such as the heterogeneity of disease and the most likely mixed origin of infections. Also, since far fewer children than adults die of complicated pneumonia in western countries, attempting to prove cost-effectiveness of the technology when applied to pediatric pneumonia might be problematic. However, the former does not apply to pediatric pneumonia in LMIC, where this disease fatally affects an inordinate number of children, and where antimicrobial resistance disproportionally affects treatment failure. It therefore deserves investments in testing and improving low-cost diagnostic sequence technology for pediatric pneumonia in LMICs as well; for too long these children came last in benefiting from medical innovations, let them now come first.
About the author
Professor Debby Bogaert is the Chair of Paediatric Medicine at the Centre for Inflammation Research, University of Edinburgh, and works as a paediatric infectious diseases specialist at the Royal Hospital for Sick Children Edinburgh. She also leads a research group at the University Medical Center Utrecht, Netherlands. Her research groups have a major focus on investigating the physiology and pathophysiology of respiratory infections and inflammation from an ecological perspective, with the ultimate goal to design new or improved treatment and preventive measures for respiratory infections in susceptible populations. To this purpose, the teams use a fully translational approach, combining epidemiological, molecular microbiological, immunological and systems biology approaches to answer their research questions.