Table 2.

Studies of manuka honey: findings, gaps, and future studies.

Study	Findings to date	Gaps and controversies	Suggested future studies
Chemical analyses	MGO is responsible for most but not all of the antibacterial and anti-biofilm activity in manuka honey; hydrogen peroxide is responsible for most but not all of the activity in non-manuka honeys; leptosin may modulate activity; phenolics can act as antioxidants and promote wound healing.	Constituents that modulate activity, produce synergy between honey and antibiotics and promote wound healing are not known.	Fractionation, purification, and testing of constituents alone and in various combinations.
Pathogen inhibition	Manuka honey inhibits growth of all bacterial pathogens tested, prevents biofilms and can disperse and eradicate pre-formed biofilms.	Few studies on non-bacterial pathogens and on mixed-species biofilms.	Test honey on pathogenic fungi, parasites, and viruses; analyze biofilms produced by consortia of bacteria and yeasts.
‘Omics and systems biology	Treatment with manuka honey results in a unique signature of differential gene expression with down-regulation of stress response and virulence-related genes.	Analyses restricted to differential expression; only single time-points explored; only performed in E. coli and S. aureus; very little validation.	Contextualize using advanced systems biology tools; assess dynamics of cell response; validate using quantitative PCR and gene deletion/overexpression strains.
Ultrastructure	Vastly different morphological alterations in different bacterial species; suggests S. aureus fails to complete cell cycle; P. aeruginosa has extensive cell degeneration and lysis.	Few species/strains analyzed to date.	Extend to additional strains and species including mixed-species biofilms and wound biopsies.
Drug interactions	Manuka honey is synergistic and/or enhances activity of a variety of antibiotics, prevents development of resistance and renders resistant strains susceptible; MGO not responsible for synergy.	Only S. aureus and MRSA tested to date and substantial differences occur among strains; substance/s causing synergy unknown.	Extend to additional strains and species; test honey fractions to determine compound/s responsible for synergy; determine strain-specific differences in response using ‘omics approaches.
In vivo use and clinical trials	Case studies and use of therapeutic manuka honey on wounded animals shows honey can clear infections and promote wound healing.	Robust clinical trials have not been undertaken.	Use data obtained from above to inform treatment and devise clinical trials.