Honey Responders and Non-Responders in Individuals with Overweight and Obesity: A Pilot Study in Precision Nutrition

Background/Objectives: The high prevalence of obesity and obesity-associated diseases in the United States and worldwide places a tremendous burden on public health. Although lifestyle interventions, such as calorie-restricted diets and increased exercise, are generically recommended to individuals with overweight and obesity, it is well acknowledged that individual responses to the same lifestyle intervention vary significantly, underscoring the importance of individualized or precision nutrition-based approaches in obesity management. Methods: In a recent randomized, parallel-arm pilot study, manuka honey (21 g) was given daily to overweight and obese participants aged 40–75 years for four weeks. The levels of plasma interleukin (IL)-6 at the baseline and after honey treatment were measured. The 14 female participants were stratified into responder (R) and non-responder (NR) groups, based on their circulating IL-6 level changes. Plasma and fecal samples from the R and NR groups were subjected to untargeted metabolomics analysis and 16S rRNA analysis, respectively. Results: Among the female participants with overweight and obesity, 50% had reduced plasma levels of IL-6 after honey intake, and other 50% showed no such responses. Untargeted metabolomics analysis demonstrated that 22 metabolites markedly increased and eight decreased in the R group, relative to the NR group. A decrease in circulating glutamic acid could potentially predict the responsiveness to honey intake. 16S rRNA analysis showed that 23 and 14 genera were uniquely enriched in the R and NR groups, respectively. Enriched Bacteroides and Akkermansia in the R group are capable of metabolizing glutamic acid and thus may contribute to the decreased level of circulating glutamic acid. Conclusions: In this pilot study, participants with overweight and obesity showed different responses to honey intake. Circulating glutamic acid may have the potential to predict the responsiveness of patients to honey and provide guidance for precision nutrition-based dietary intervention.