Microbes in Skin Probiotics

Review of Research on Skin Probiotic Microorganisms

Bifidobacterium lactis

Bifidobacterium lactis is a gram-positive rod-shaped bacterium found in the large intestines of cows, cats, and humans. This bacteria was isolated from a breastfed infant in the 1980s. It is a subspecies deriving from Bifidobacterium animalis. This bacterium was sequenced because of the boom of probiotic use and its possibility to be a good bacteria to add to the human gut microbiome. B. lactis is considered a good probiotic because it expresses fermentation activity, it has a high aero tolerance and good stability. It can be found in formula, supplements, and fermented milk products globally. It also can go undetected orally because it does not have a taste or a specific texture that would make it a difficult consumable. It is able to survive the stressful environment of the gastrointestinal tract by having a high acid and bile salt tolerance. A specific strain of B. lactis named BB-12 expresses all of the main qualities of being a productive probiotic. It can inhibit pathogens, enhance barrier function, and aid in immune interactions (Jungerson et. al 2014).

Probiotics are able to interact with the immune system due to the interactions through the colonization of the gut mucosa and the gut-associated lymphatic tissue. Keeping the gut in a proper symbiotic environment reduces the event of gut dysbiosis that can lead to inflammatory events in other parts of the body including the GI tract. The metabolic processes of B. lactis can be attributed to the release of short-chain fatty acids (SCFA). Since B. lactis is a fermenter it can produce SCFAs as a byproduct of fiber breakdown. These SCFAs are used by the body and can decrease skin inflammation and other inflammatory processes due to their ability to influence macrophages, neutrophils, and other leukocytes. The Bifidobacteria family has also been known to help encourage the growth of immune cells like dendritic cells and T cells and are introduced early in life through breastfeeding. B. lactis and other organisms in this family have been able to decrease some inflammatory skin conditions as well as food allergies (Mann et al. 2020).

In a study to look at the use of probiotics to treat atopic dermatitis, commonly known as eczema, researchers used B. lactis in association with a Lactobacillus strain. Their hypothesis was that a probiotic regimen of B. lactis and Lactobacillus casei would cause improvement in atopic dermatitis symptoms. A population of patients ranging from 4-17 years of age took the placebo or probiotic for 12 weeks. Following the 12-weeks the patients that received the probiotic had an increase in B. lactis found in their stool samples. When looking at this increase it lead to the belief that B. lactis has the ability to decrease the gut bacteria that typically will aggravate atopic dermatitis. The decrease in the bacteria aggravating AD and the increase in the B. lactis lead to a lower percentage of AD symptoms in these patients that received the probiotic course of treatment (Climent et. al 2021). This is a newer study and in the past opposing results have been found. Another study aimed at examining AD in infants, found that Lactobacillus decreased AD flare-ups, but B. lactis had no overall effect. If there was an effect found it would not have been beneficial due to B. lactis being absent in stool samples when they were collected more than 3 days after probiotic ingestion (Wickens et al 2008).

In conclusion, a growing body of research shows evidence that B. lactis helps to cultivate a healthy gut and stimulates down-regulation of inflammatory processes that are unnecessary in various systems in the body. It is able to establish a balanced gut microbiome and is a beneficial probiotic in some studies looking at atopic dermatitis. Due to its capability to communicate with the immune system and produce SCFAs it does serve as an aid to decrease inflammation which may translate to skin inflammation in the future.

Lactobacillus rhamnosus

Lactobacillus rhamnosus is a bacteria that is naturally found in our gut. It is an anaerobic or facultative anaerobic Gram-positive rod that is commonly found in the human gastrointestinal tract and vaginal tract (Albarillo, F. S et al., 2020). L. rhamnosus is being researched as a probiotic-based treatment for atopic dermatitis. Atopic dermatitis is a chronic inflammatory skin disease that is due to mutations of the filaggrin gene, which is located in the epidermal differentiation complex. The skin inflammation can be caused by many factors such as allergens, dust mites, changes in weather, and stress. This skin condition affects 5-20% of children worldwide and the incidence continues to increase each year. (Wu, Y.-J et al., 2017). These have been used in medical practice as immunomodulators. Lysates of L. rhamnosus can increase tight-junction barrier resistance by modulating the specific protein complexes. Studies have been conducted and shown that Lactobacilli lysates can re-epithelialize keratinocytes (Puebla-Barragan, S., & Reid, G. 2021) A study was done to test the lysates of L. rhamnosus on skin barrier function in reconstructed human epidermis, Keraskin. Keraskin was purchased from Biosolution Co. and consists of human keratinocytes as a functional multilayered epidermis with the essential lipid composition. A L. rhamnosus (LR) lysate when used topically in this study has been shown to increase epidermal differentiation markers. The LR lysate, when applied to Keraskin every other day for 16 days, showed that the treated tissues have more ordered and denser stratum corneum when compared with the control. The treated tissues also underwent immunofluorescence staining with the antibodies against two specific tight junction proteins: claudin1 and occludin. The IF images showed an increase in both tight junction molecules after treatment with the LR lysate. To further analyze this, immunohistochemistry with antibodies against cytokeratin 5, 1, 10, loricrin, and filaggrin was performed. K5 and K1 showed an advancement into the upper layer of the epidermis along with increasing intensity of filaggrin in LR treated Keraskin (Jung, Y.-O et al., 2019). A randomized double-blind, placebo-controlled study was conducted at two sites in Taiwan to investigate the efficacy of L. rhamnosus in children from the ages 4-48 months. The study suggests a positive effect of probiotic supplementation in patients with atopic dermatitis (Wu, Y.-J et al., 2017). The data showed a greater decrease in the intensity and severity of AD for the population who received at least one dose of the treatment of Lactobacillus rhamnosus. However, there were many limitations because the onset of probiotics may be more significant if the treatment lasts more than 8 weeks. Also, AD can have recurrence and fluctuates in the short term. However, when treatment with L. rhamnosus was used orally in combination with topical corticosteroids, it showed a synergistic effect in this study (Wu, Y.-J et al., 2017). Another study was performed in Wellington and Auckland, New Zealand to test that probiotic supplementation by L. rhamnosus administered to mothers from 14 to 16 weeks gestation until delivery and continuing until 6 months postpartum, if breastfeeding, will reduce the prevalence of infant eczema and atopic sensitization and the prevalence of maternal GDM, BV, and GBS vaginal colonization before birth (Barthow, C et al., 2016). However this study has not provided its data as it is ongoing. Overall, L. rhamnosus is currently being researched for usage as a probiotic to help treat skin conditions like atopic dermatitis. Since this bacteria is naturally found in the gastrointestinal tract as well as the vaginal tract, it shows promise as a potential treatment for this condition. Studies have been done like the ones above that have strong data supporting the use of L. rhamnosus, but more studies should be completed in order to show replicable data in human based models.

Lactobacillus acidophilus

Lactobacillus acidophilus is a gram positive rod-shaped bacteria that is typically found in human and animal gastrointestinal tract and mouth (Badet and Thibauld, 2008). While more well known for its probiotic uses in dairy products such as yogurt, L. acidophilus has been recently receiving attention for its uses in skin care as an anti-wrinkle agent.

L. acidophilus was first noticed for potential skin treatments alongside the proposed gut-brain-skin theory by John H. Stokes and Donald M. Pillsbury around the 1930s. The theory proposed that gastrointestinal microbiome and function were tied to mental health disorders and skin conditions such as acne. Chronic emotional states alter the gastrointestinal tract, which disturb the intestinal microbial flora and increase the risk for intestinal permeability. The resulting impact is an increase in inflammation to the skin. The proposed solution was 'the direct introduction of acidophil organisms in cultures,' which could be distributed with tablets or drinks. Formal studies were conducted starting in the 1960s, often with oral probiotic tablets containing L. acidophilus in combination with other bacteria such as L. bulgaricus and B. bifidum. While flawed, these studies indicated a strong correlation between the intake of bacteria and the reduction of inflammation acne and other skin lesions (Bowe WP et. al. 2011).

More recent studies have turned their focus on tyndalized L. acidophilus's effects on UV damaged skin as an anti-wrinkle agent. A study in 2016 focused on UVB radiation on the skin of hairless mice and the potential effects from orally administered tyndalized L. acidophilus tablets. Tyndallization is an outdated sterilization process that heats a solution at or just below boiling temperatures, and is used today to kill bacteria as well as any endospores possibly contained inside. The mice exposed to UVB rays experienced significant skin dehydration and transepidermal water loss, however thanks to frequent ingesting L. acidophilus beforehand, some of the hydration and water retention was retained in the skin and the overall damage was not as severe. Skin samples also revealed a more even collagen distribution among mice that received the L. acidophilus tablets, resulting in a lower level of wrinkling as a result of UV irradiation. A western blot has revealed that the MMPs, specifically MMP-1 and MMP-9, alongside signaling parts involved in the p38 MAPK pathway, have a reduced expression. These enzymes are strongly expressed as a result of UV irradiation, so further investigation on how L. acidophilus reduces the expression could be explored (Im AR et al. 2016).

Further studies have explored L. acidophilus effects on human cells alongside mice cells. Human keratinocytes and human dermal fibroblast cells were exposed to UVB irradiation to observe the skin's biological response to tyndallized L. acidophilus, specifically L. acidophilus-KCCM12625P. The cell viability of HaCaT and HDF cells saw a recovery from ROS generation due to UVB irradiation after exposure to L. acidophilus, indicating antioxidant effects. ROS induced wrinkles as a result of induction of MMPs and elastase enzymes were also inhibited in a dose-dependent manner. The melanogenesis of B16F10 mice cells through UVB irradiation was also observed, and indicated that L. acidophilus does not directly affect tyrosinase activity but has anti-melanogenesis effects through regulation of cAMP signaling pathways (Lim HY et. al. 2020).

The overarching conclusion is that L. acidophilus does have potential positive benefits to skin care, with a particular emphasis on skin protection from UVB irradiation damages. L. acidophilus has been found to aid in the reduction of dehydration, water retention, and inhibiting ROS induced wrinkles from mice models. This is achieved through impacting the p38 MAPK and cAMP pathways. Human cell culture models also saw a recovery from ROS induced wrinkles through the known molecular "aging" markers. However, studies using human subjects are either lacking or flawed. The early studies often either did not have a control for comparison, or were difficult to evaluate due to different language or accessibility. Nevertheless, these findings provide a solid basis for future analysis on L. acidophilus's role in skin care.