# Influence of Ingestion of Lactulose on \(\gamma\)-Lactones Enanating from Human Skin Surface
## 4 Discussion  
This study provides novel evidence for the influence of lactulose ingestion on sweet-smelling gases released from the human skin surface. The fluxes of dermal emission of C10 and C11 lactones increased as the number of bifidobacteria increased. C10 lactone has a strong peach-like odour, and C11 lactone has a coconut and/or fruity smell [22]. Lactulose products are commercially available in the form of syrup, beverages, and yoghurt. Thus, by integrating our previous knowledge of ammonia [6], the daily ingestion of lactose probably contributes to improving body scent by increasing the dermal emission of sweet-smelling lactones and decreasing pungent odorous ammonia. [PERSON] et al. [16] reported an increase in the dermal emission of C11 lactone in aged British people after oral intake of New Zealand blackcurrant powder containing anthocyanin. However, the mechanism underlying dermal \(\gamma\)-lactone formation is not fully understood. One possible mechanism is that the microbiota form lactones on the human skin surface. _Malassezia furfur_ (formerly known as _Pityrosporum_, a lipophilic yeast) commonly colonises the human skin surface, especially the scalp, and can cause mycosis and other adverse health disorders. [PERSON] et al. [23] found that the genus _Malassezia furfur_ produced volatile C8-C12 lactones during growth on culture media supplemented with human sebum. They also suggested that the production of \(\gamma\)-lactones may serve as a biomarker in the identification of the genus _Malassezia furfur_ on the human scalp, where abundant serum and other nutrients [23] are present. However, it is difficult to link the fungal activity on the human skin surface and ingestion of lactulose, as well as New Zealand blackcurrant, due to a lack of sufficient evidence. Another possible mechanism is the promotion of fatty acid oxidation mediated by the SCFAs produced in the colon. Acetate, propionate, and butyrate constitute 95% of the microbial-derived SCFAs [17]. After being produced by gut microbiota, SCFAs are initially used by intestinal epithelial cells as an energy source. Residues are subsequently transported to blood vessels in a concentration-dependent manner and then migrate to the liver and muscles through blood circulation [17]. SCFAs do not directly travel from the blood to the skin surface because they exist in non-volatile chemical forms such as acetate, propionate, and butyrate salts in weakly basic blood plasma. However, when they emerge with perspiration, an acidic environment on the skin surface (pH = 5-6) can release these SCFAs as free acids into the air, because their pKa is approximately 4.8. Therefore, the dermal emission of acetic acid appears to be a good biomarker for sweating [24]. The composition of SCFAs in the intestine is not necessarily reflected in the composition of dermal emission fluxes because there may be other potential emission routes of dermal SCFAs, such as bacterial activity on the skin and food metabolism. However, it should be noted that the composition of the three dermal SCFAs apparently changed after ingestion of lactulose, as shown in Figure 4, and the fluxes of cutaneous emission of acetic acid and/or the sum of the three SCFAs showed an increasing trend with elapsed days. Recently, SCFAs have attracted increasing interest due to their effect on host adiposity and contribution to obesity by increasing fatty acid oxidation [17,18]. [PERSON] et al. [25] reported that dietary SCFAs can act as signalling molecules in the body, inducing a peroxisome proliferatorator-activated receptor-gamma (PPARy)-dependent switch from lipid synthesis to lipid utilisation by enhancing oxidative metabolism; hepatic \(\beta\)-oxidation of \({}^{14}\)C-labelled palmitic acid, a model fatty acid, was significantly enhanced by the addition of these three SCFAs into liver homogenates.