The epithelial of mammalian skin is a self-regenerating tissue that provides the first line defense mechanism between an organism and its environment [1]. Epidermis should maintain homeostasis between proliferation and differentiation to perform this function greatly [2]. The basal layer borders with an ECM-rich basement membrane below. Proliferative keratinocytes lie in basal layer. These cells express genes encoding integrins, Epidermal Growth Factor Receptor (EGFR; also referred to as ErbB1), and also the structural keratins 5 and 14 (K5 and K14) [3]. Well-ordered transcriptional regulation of those genes can control the epidermal homeostasis [4]. Skin homeostasis rules an important factor in physiological aging process.
Aging is initiated when our body lost its homeostasis control in the cell and regression process more takes place rather than growth. Aging is a slow process that contributes to deterioration of cells and tissues functions, and it could be initiated by both genetics and environment factors contribute to the event of aging [5]. Aging process is happens in every tissue of an organism with no exception include human skin tissue. Skin aging is usually characterized by wrinkles, unwanted spots, and decrease in elasticity. The rise of skin collagen degradation rate makes the collagen structure fragmented. Skin aging happens when the degradation of collagen reduces mechanical tension of the tissue [6].
In human, skin aging become a important issue in modern society because everyone want to keep their beauty and stay young. Thus, there is growing demand of alternative treatment for skin health and aesthetic like : nutrition, exercise, stress management, medication, plastic surgery, etc. Nutrition is one of the friendly and non invasive approach to counter the skin aging. Recently, fermented milk could addres those expectation, however the link mechanism is remain unclear.
Michelle D. Holmes had reported that dietary behaviour which higher energy, protein, and milk content were associated with higher levels of IGF-I and IGFBP3 levels (7). In addition, dietary modification of intestinal microflora by yogurt or Lactobacilli supplementation reduce fecal β-glucuronidase activity, and correlated with estrogen metabolism (8). Thus, by facts that fermented milk could alters and stimulated increase ratio of good gut microbiota and interestingly growth factor like IGF-1, it is interesting to explore its role on Epidermal growth factor (EGF) in the skin.
EGF is an important factor for maintaining normal skin growth, regeneration and indirectly helps its physiological function. EGF is a facilitator of the construction of skin tissue through dermal regeneration, proliferation, differentiation, and migration of keratinocyte, endothelial cells, and fibroblast [9]. Interaction between EGF and the EGFR initiates downstream signalling pathways that induce proliferation, differentiation, survival, or motility of the cell [10]. Attachment and binding of EGF ligand to EGFR induces the dimerization of receptor. The process of dimerization then activates phosphorylation of the intracellular domain of tyrosine kinase [11]. Phosphorylated tyrosine kinase then activates various downstream signalling pathways including Ras/MAPK, PLCγ1/PKC, PI(3)kinase/Akt, and STAT pathways [12]. The pathways of the EGF activation have been known to affect the skin physiology. Phospholipase C (PLC) pathway elevates intracellular calcium[13] which improves the formation of tight junction and stratum corneum barrier [14]. PI3K/Akt pathway increases the level of type I procollagen [15] which has an effect of minimalizing intrinsic skin aging [16]. Meanwhile, Src pathway promotes the expression of MMP-1, resulting in the collagen degradation in human fibroblast cells [17] .
Source of fermented milk might determine the nutrient content, and its fermented content results will be correlated with EGF. For instance, Soy, Glycine max, contains the great number of phytoestrogen and polyphenols [18]. One of the phytoestrogen is isoflavone. Isoflavone induces high expression of EGFR, thereby improving wrinkle reduction and collagen stimulation [19]. A conduction of cell culture experiment showed that isoflavones had increased collagen, elastin, and tissue inhibitor of metalloproteinases (TIMP) genes expression [20]. Soybean can be processed as soy milk by soaking, draining and grinding and filtering [21]. Various combinations of cow and soya milk fermented by various bacteria have been known to have ability to increase surface area of villi and villus height of the intestine, thus increasing intestinal absorptive function [22]. Probiotics are living microorganisms in gastrointestinal tract which give benefits to the host [23]. Overexpression of pro-inflammatory cytokine IL-6 tends to happen in the aging gut, which affects the inflammatory rate in aging skin [24]. It happens because aging gut shows lower microbial biodiversity, which is associated with an increase of pro-inflammatory bacteria and decrease of beneficial bacteria [25]. Probiotics can improve the condition of -microbial dysbiosis in aging gut and establish a health-promoting strains. Consumption of probiotics consisting Galacto-oligosaccharides (GOS) increases CD44, TIMP-1, and type 1 collagen, which are the markers of dermal cell adhesion and matrix formation, thus improving the rejuvenation of skin. GOS switching unfavourable amino acid metabolism and phenols production by becoming an additional source of metabolism for gut microbials [26].
Another source is cow milk instead of soy, however there is a different between cow and soy. Formula and bacteria type for fermentating cow milk is different with soy milk. Lactic acid bacteria is used for fermentation because it easily convert lactose into glucose and galactose of cow milk. Others bacteria are also commonly used for the milk probiotics, like Lactobacillus bulgaricus and Lactobacillus acidophilus [27]. Some products replace Lactobacillus bulgaricus with Bifidobacterium spp. due to the difference of metabolism isomer product. Bifidobacterium spp. produces the isoform of D-(+)-lactic acid which has an active effect in physiology. Meanwhile, Lactobacillus bulgaricus produces D-(-)-lactic acid which is physiologically inactive [28]. The digestion of lactose can be enhanced by the presence of Streptococcus thermophiles through the activity of its microbial β-galactosidase [29].
By seeing this importance, combination of Bifidobacterium spp and Lactobacillus acidophilus has shown the potential to increase increase the activity of lipase and protease [30]. The yoghurt formulation of Lactobacillus acidophilus and Bifidobacterium spp. also increase the non-pathogenic population and decrease the pathogenic bacteria in colon [31] In the other hand, adding beneficial microorganisms to the gut could prevent or delay some age-associated diseases by improving the immune response or by producing bioactive metabolites. Unfortunately, there is limited information about effect of formulated fermented milk and green bean on skin physiological homeostasis .
Thus, in this present study, we want to explore different formulation of bacteria starter in cow milk and soy milk for initiating fermentation process and stimulates optimal formula to skin maintenance.