# Influence of Ingestion of Lactulose on \(\gamma\)-Lactones Enanating from Human Skin Surface
## 1 Introduction  
Lactulose (4-O-\(\beta\)-D-galactopyranosyl-\(\beta\)-D-fructose) is a simple disaccharide made up of galactose and fructose produced by isomerisation of the milk sugar lactose [1, 2]. Clinical doses of lactulose are used for the treatment of high ammonia levels in blood, which leads to hepatic encephalopathy and constipation [3]. Meanwhile, lactulose at low doses (<10 g d\({}^{-1}\)) is used as a prebiotic which promotes an increase in the abundance of _Bifidobacterium_ in the human gut and is thought to promote human health by increasing the production of beneficial metabolites such as lactic acid and short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate in the colon [4, 5]. Our previous study [6] demonstrated the influence of lactulose at a food dosage of 4 g d\({}^{-1}\) on ammonia emanating from the skin surface of healthy subjects. When ammonia is formed in the human body by internal metabolism, it rises to the skin surface with perspiration (sweet gland route) and/or directly in volatiles from the blood through cutaneous layers (blood route) [7, 8]. This emanation can cause a characteristic pungent body odour [7, 8]. A significant decrease in the emission of skin ammonia was observed eight days after lactulose ingestion, andthe flux of dermal emission of ammonia decreased as the number of faecal bifidobacteria grew [6]. However, no study has reported the influence of lactulose on human skin gases other than ammonia.  
\(\gamma\)-lactones are volatile cyclic esters derived from fatty acid metabolism [9; 10]. These compounds are naturally present in fruits, including peaches, plums, pineapples, and strawberries, and contribute to their complex aroma and flavour [10; 11]. For example, \(\gamma\)-octalactone (C8), \(\gamma\)-nonlactone (C9), \(\gamma\)-decalactone (C10), and \(\gamma\)-undecalactone (C11) are key odorants in peach and apricot [12; 13]. Biosynthetic studies indicate that several pathways originating from the \(\beta\)-oxidation of middle- and/or long-chain fatty acids, such as oleic acid, linoleic acid, and palmitoleic acid, are responsible for the structural diversity of lactones [14]. Recently, these \(\gamma\)-lactones have also been found in a trace gas mixture emanating from the human skin surface [15; 16]. They contribute to sweet body scents, particularly in young females, because a greater dermal emission was found in teenage girls [15]. Meanwhile, SCFAs, metabolites of gut microbiota, have attracted increasing interest due to their effect on host adiposity and contribution to anti-obesity by increasing fatty acid oxidation [17; 18]. Therefore, when fatty acid oxidation is enhanced by changes in the gut microbiota, dermal emission of \(\gamma\)-lactones can be affected.  
In this study, we aimed to investigate the influence of oral ingestion of lactulose with a food dosage of 4 g d\({}^{-1}\) on the amount of sweet-smelling \(\gamma\)-lactones released from the skin surface of healthy subjects. The emission mechanism of \(\gamma\)-lactones was also discussed by measuring dermal emissions of SCFAs as their free acid forms.