The Impact of Antibiotics and HAMLET on Microbial Ecology: From Ex Vivo to In Vivo Studies

Abstract

Bacteria use their own strategies to survive when exposed to antibiotic treatment. One of the most serious public health problems we face today is that antibiotics are unable to kill or inhibit many of the disease-causing bacteria but instead kill many good and healthy bacteria. This leads to an imbalance in the microbiome, which can have a detrimental effect on health. A natural component from breast milk, called HAMLET, has been shown to have the ability to kill some of the disease-causing bacteria as well as resensitize bacteria to antibiotics they were previously resistant to.

This Ph.D. project provides valuable insight into the effects of antibiotics and HAMLET on the oral microbiome, biofilm formation, antimicrobial resistance and adaptive immune response. The oral microbiome is the second largest microbiome in the body. Our understanding of how antibiotics affect the oral microbiome and the resistome is essential for understanding the role of the oral cavity in the transfer of disease-causing bacteria to other parts of the body, e.g. the upper and lower respiratory tract. In addition, the oral microbiome is known to contain the highest number of antibiotic resistance genes in the body.

The findings in this thesis address the risks of long-term exposure to low antibiotic concentrations, including the development of bacterial virulence, biofilm formation, and antibiotic resistance. The results of the research show that low concentrations of ampicillin and amoxicillin can increase polymicrobial biofilm formation in the oral cavity. The combination of HAMLET and amoxicillin also has a modulatory effect on biofilm composition by promoting the growth of bacteria with probiotic and antimicrobial potential. In addition, the study reveals acquired immune responses triggered by amoxicillin, but not HAMLET, resulting in suppression of IL-17A production in lung CD4+ T cells after exposure to the pathogenic bacterium, Streptococcus pneumoniae.

The study particularly highlights the possibilities of combining in vivo and ex vivo models to better understand the dynamics and complexity of the oral microbiome in response to antibiotic treatment. The oral microbiome is unique to each person. Several factors, such as genetics, diet, and environmental influences, help shape the individualized microbiome. This is a recognized challenge in microbiome studies, where the results can vary from donor to donor. Metagenomic studies have been revolutionary in gaining insight into the dynamics of the oral microbiome. Combining these methods with clinical studies looks promising for the future.