## 3 Discussion
These strains efficiently produce lactic acid, butanoic acid, hexanoic acid, and corresponding ethyl esters [36]. Some LAB also use L-leucine to produce 2-hydroxy-4-methyl-pentanoic acid [37], which was exclusively detected in Chinese baijius in considerable amounts. _Bacillus_ sp. including _B. subtilis_, _B. licheniformis_, and _B. amyloliquefaciens_ are involved in Daqu production and the following stacking fermentation. _Bacillus_ sp. are not only known as the producer of various hydrolases, but also as efficient producers of 2,3-butanediol [38; 39]. _B. subtilis_ has been reported to produce tetramethyl-pyrazine [40], which was exclusively detected in Chinese baijius. In contrast, _Saccharomyces cerevisiae_--known to produce ethyl octanoate, ethyl decanoate, glycerol, and minor higher alcohols, fatty acids, and aldosterone [23; 41]--was the main microorganism in the production of Western liquors. Aging vessels is another important factor. Many important flavor compounds come from the aging vessels, such as oak lactone (also known as 2(3H)-furanone, 5-butyldihydro-4-methyl-, cis-), vanillin, and vanillic acid. These compounds originally resided in oak barrels in which most Western liquors were aged [42], whereas the Chinese baijius were aged in pottery jars. Hence, these compounds can be only detected in Western liquors (Table S1 and S2). In addition, artificial factor contribute to the compositional difference between Chinese baijius and Western liquors. Sugars, the main non-volatile compound in Western liquors, are commonly added artificially to aged Western liquors such as brandy [11], rum [43], and whisky [44], giving them an amber coloration that is attractive to consumers. The artificially added sugar in distilled liquors is collectively called caramel. The chemical composition of caramel is complex due to the large number of substances produced as a result of pyrolysis of carbohydrates, such as sucrose, glucose, or starch. Caramel has been reported to be rich in advanced glycation end products (AGEs). AGEs are blamed for increasing insulin resistance and inflammation [45]. However, many bioactive compounds including aldosterone, pyrazine, alcohols, fatty acids, and ethyl esters were observed in distilled liquor [46] and most of them were detected in this study. Additionally, many of the detected benzene derivatives--such as benzofuran, benzoic acid ethyl ester, benzene acetic acid ethyl ester, benzene acetic acid ethyl ester, benzene propanoic acid ethyl ester, and phenylethyl alcohol--are known to be bioactive. An in vitro study reported that a honey that was abundant with these benzene derivatives exhibited effective antibacterial activity, especially for Gram-negative bacteria [28]. The progress of alcoholic liver disease has shown that alcohol administration can cause overgrowth of intestinal Gram-negative bacteria and increase the burden in the intestine, leading to leaky gut. Figure 5: Factors that contribute to the compositional difference between Chinese baijius and Western liquors, and representative compounds associated with each factor. In the orange core circle are the major contributing factors: raw materials, production processes, microorganisms, and aging vessel. In the middle green ring are the corresponding elements of the factors. The blue periphery ring are key compounds influenced by the core factors. The model of the production processes and microorganisms briefly describes the biochemical production pathways of a few major compounds. C7, 8 and10 represents R contains C7, C8, and C10 linear chain length, respectively; C2–C6 represent R containing C2–C6 linear chain length, respectively. SSF: simultaneous saccharification and fermentation; 2H4 MPA: 2-hydroxy-4-methyl-pentanoic acid; 2M1, 3 PDO: 2-methyl-1,3-propanediol; TMP: tetramethyl-pyrazine. Information about concentration of the compounds in this figure can be found in Supplementary Materials.