Abstract: Acne vulgaris is a common skin disorder of pilosebaceous units. The therapy for mild-to-moderate acne includes topical antibiotics, benzoyl peroxide and retinoids. In this open-label, randomized monocentric study, we compared the effcacy of LactoSporin® 2% w/w cream with benzoyl peroxide in 64 male and female subjects with mild-to-moderate acne for three weeks.
The effcacy parameters were evaluated based on the dermatologist visual assessment and instrumental measurements using Sebumeter® MPA580, Antera 3DTM and VISIA CR 2.2 and subject self-assessment questionnaires. Adverse events were recorded throughout the study period. In order to understand the mechanism of action and properties of LactoSporin, the pH stability, thermostability, antimicrobial activity and 5-alpha reductase activity were evaluated in vitro. A significant improvement was observed in the dermatological assessment of closed comedones (p < 0.0001), open comedones (p = 0.0069) and papules count (p < 0.0001) in comparison to the baseline in both LactoSporin and benzoyl peroxide groups. The antera analysis showed significant improvement in redness (p < 0.0001) and elevation (p < 0.0001) (small and medium) in both the treatment groups. The sebumeter analysis showed a significant decrease in sebaceous secretion (p < 0.0001) for LactoSporin, which resulted in reduced oiliness, pimples, acne spots and redness around the acne spot. The product was found to be safe without any irritancy. LactoSporin was stable at an acidic pH and temperature range of 70 to 90 °C, with antimicrobial activity against various pathogenic bacteria, including Cutibacterium acnes.
It was also a potent inhibitor of 5-alpha reductase activity. Thus, it can be concluded that the effcacy of LactoSporin is equivalent to benzoyl peroxide in the treatment of mild-to-moderate acne lesions and better than benzoyl peroxide for reducing the sebaceous secretion and oily, greasy nature of the skin, implying its effcacy in other sebohorriec conditions.
Conclusion : This study suggests that LactoSporin is a postbiotic that is thermostable and stable at an acidic pH. LactoSporin 2% w/w cream was a safe antiacne formulation with e cacy comparable to the standard treatment of benzoyl peroxide 2.5% gel. The onset of e cacy was very early for LactoSporin—as early as three days—especially for closed comedones, providing a quicker benefit than benzoyl peroxide. The major finding of this study shows that LactoSporin reduces the sebaceous secretion by its 5-alpha reductase inhibitory and antimicrobial properties, which are better than benzoyl peroxide and can be a potential ingredient for other Seborrheic conditions as well. Considering the clinical e cacy, continuous treatment and patient satisfaction, LactoSporin is highly suitable for treating subjects with mild-to-moderate acne vulgaris. Further studies on a larger sample in multiple ethnic populations may substantiate our findings.
Keywords: primary skin irritation patch test; antiacne; postbiotics; LactoSporin®; benzoyl peroxide
Study for LactoSporin
Novel Topical Application of a Postbiotic, LactoSporin®, in Mild to Moderate Acne: A Randomized, Comparative Clinical Study to Evaluate its Effcacy, Tolerability and Safety - Muhammed Majeed, Shaheen Majeed, Kalyanam Nagabhushanam, Lakshmi Mundkur, H. R. Rajalakshmi, Kalpesh Shah and Kirankumar Beede - Cosmetics 2020, 7, 70

Background: Probiotics and their products are increasingly used in skincare in recent years. Postbiotics are defined as any substance derived through the metabolic activity of a probiotic microorganism, which exerts a direct or indirect beneficial effect on the host. The extracellular metabolites of probiotic bacteria have antimicrobial activities, protect against acne, and improve skin condition. We studied skin protective activities of the extracellular metabolite (LactoSporin) of a spore-forming probiotic Bacillus coagulans MTCC 5856 in vitro. Methods: LactoSporin was evaluated for antioxidant activity by free radical scavenging activity and reactive oxygen quenching activity in human dermal fibroblast cells. Protection of fibroblasts from UV-induced apoptosis and cell death was studied by flow cytometry and neutral red uptake assays. Enzyme inhibition assays were carried out for collagenase, Elastase, and Hyaluronidase. Gene expression studies were carried out using polymerase chain reaction. Results: LactoSporin showed antioxidant activity and was found to protect skin cells from UV-induced apoptosis and cell death. LactoSporin inhibited collagenase, elastase, and hyaluronidase activity and upregulated the expression of hyaluronan synthase, transforming growth factor and epidermal growth factor, which are associated with extracellular matrix integrity.
Conclusions: These results suggest LactoSporin is a skin protective postbiotic with wide application in cosmetic formulations.
The results of the present study suggest the potential of LactoSporin in improving skin health by divergent mechanisms. LactoSporin has also been shown to have antimicrobial properties and reduce acne severity in a clinical study. By reducing oxidative stress and preserving extracellular matrix proteins, LactoSporin may reduce the appearance of wrinkles and sagging of skin. Future clinical studies with formulations containing LactoSporin may further substantiate the results of these preliminary observations.
Keywords: postbiotic; LactoSporin; Bacillus coagulans MTCC 5856; antioxidant; anti-inflammatory; extracellular matrix; skin aging
Study for LactoSporin
Skin Protective Activity of LactoSporin-the Extracellular Metabolite from Bacillus Coagulans MTCC 5856 - Muhammed Majeed,Shaheen Majeed,Kalyanam Nagabhushanam,Lincy Lawrence 1,Sivakumar Arumugam and Lakshmi Mundkur - Cosmetics 2020, 7(4), 76

Abstract : Current research on the complex interplay between the microbiota, the barrier function and the innate immune system of the skin indicates that the skin's microbiota have a beneficial role, much like that of the gut microflora. As a consequence, interest in strategies beyond antibiotica that allow a more selective modulation of the skin microflora is constantly growing. This review will briefly summarize our current understanding of the cutaneous microbiota and summarize existing information on pre- and probiotic strategies for skin.
Prebiotics and probiotics for human skin, Journal of Dermatological Science, 54 (2009) 1-5, Jean Krutmann

Three strains of Lactobacillus, identified as Lactobacillus acidophilus, Lactobacillus gasseri, and Lactobacillus jensenii, were selected from among 70 isolates from the vaginas of healthy premenopausal women for properties relevant to mucosal colonization or antagonism. All three self-aggregated and adhered to epithelial vaginal cells, displacing well-known vaginal pathogens, such as G. vaginalis, and inhibiting the growth in vitro of Escherichia coli and Streptococcus agalactiae. The surface components involved in self-aggregation appeared to be proteins for L. gasseri and lipoproteins for L. acidophilus and L. jensenii, as judged by susceptibility to treatment with appropriate degrading enzymes. The factors responsible for adherence to epithelial vaginal cells seemed to be glycoproteins (L. acidophilus and L. gasseri) and carbohydrate (L. jensenii). The receptors of the vaginal cells were glycolipids, which presumably were the targets of the competition observed between the lactobacilli and the pathogenic microbes.
In conclusion, the lactobacilli used in this study may protect the vaginal epithelium through a series of barrier (self-aggregation, adherence) and interference (receptor binding interference, coaggregation with potential pathogens) mechanisms. Consequently, they may be excellent candidates for eventual use as prophylactic agents. Studies to further evaluate their feasibility as such are under way.
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Adherence of Human Vaginal Lactobacilli to Vaginal Epithelial Cells and Interaction with Uropathogens - INFECTION AND IMMUNITY, 0019-9567/ 98 May 1998, p. 1985–1989. S Boris 1, J E Suárez, F Vázquez, C Barbés

Criteria for screening probiotics such as bile tolerance and resistance to acids were studied with 13 spore-forming lactic acid producing bacteria. Different strains of Sporolactobacillus, Bacillus laevolacticus, Bacillus racemilacticus and Bacillus coagulans grown in MRS broth were subjected to low pH conditions (2, 2.5 and 3) and increasing bile concentrations. Among these microorganisms, Bacillus laevolacticus DSM 6475 and all Sporolactobacillus strains tested except Sporolactobacillus racemicus IAM 12395, were resistant to pH 3. Only Bacillus racemilacticus and Bacillus coagulans strains were tolerant to bile concentrations over 0.3% (w/v)
Keywords: Sporolactobacillus; Bacillus laevolacticus; Bacillus racemilacticus; Bacillus coagulans; Bile resistance; pH tolerance
Acid and bile tolerance of spore-forming lactic acid bacteria. B Hyronimus, C Le Marrec, A H Sassi, A Deschamps, International Journal of Food Microbiology 61 (2000) 193–197

Necrotizing enterocolitis (NEC) is an inflammatory bowel disease largely affecting low birth weight, premature infants. Once acquired, NEC is accompanied by significant mortality and morbid sequelae. Our understanding of the pathophysiology of NEC continues to evolve, and the development of NEC is likely multifactorial with resultant bowel injury mediated through a final, common inflammatory pathway. The predisposition for NEC appears to involve the interplay between intestinal integrity and function, enteral feeding and bacterial colonization, and regulation of the gastrointestinal and systemic inflammatory response. Commensal organisms or probiotics have been shown to be crucial in the development and modulation of each of these factors within the intestinal epithelium. As a result, probiotic supplementation has been proposed as a promising new intervention for the prevention of NEC. To understand the potential utility of probiotics in NEC, we will discuss: the components of gut defense; the role of the intestinal ecosystem in modulating immunity and inflammation; bacterial colonization patterns in the preterm infant compared with patterns seen in the healthy, full-term infant; the evidence for probiotic use in other populations and diseases; and finally, the evidence of probiotic use specific to the preterm infant and NEC.
KEYWORDS : probiotics, necrotizing enterocolitis, Lacobacillus, Bifidobacterium, Microflora, bacterial colonization, infant, prematurity
In conclusion : The cumulative evidence for probiotic supplementation in preterm infants for the prevention of NEC is very promising. Large, randomized controlled trials have shown effectiveness of probiotic supplementation in reducing the incidence of NEC. Just as encouraging, when NEC was present in the probiotic supplemented group of infants, NEC severity and mortality were decreased compared with controls. The fact that NEC could not be completely ameliorated with probiotic supplementation is consistent with the likely multifactorial etiology of NEC. However, this significant decrease in the number of NEC cases in addition to the decreased illness severity and mortality is worth pursuing. NEC severity is related to poor long-term neurodevelopmental outcomes,1 thus modification of the expression of NEC by probiotic supplementation may also improve long-term outcomes in NEC survivors. However, as additional trials move forward to study the role of probiotics in the prevention of NEC, concurrent evaluations for both short-term and long-term safety need to be included. Other ongoing issues and challenges include determining the most effective probiotic or combination of probiotics and dosing regimen. Heat-killed probiotics, probiotic DNA or proteins, or genetically modified probiotics have been shown to have similar benefits to the intestinal immune system as live probiotics. 104-107 As we learn more about the use of probiotic products in lieu of live, whole organisms, the FAO/WHO definition of probiotics may need to evolve. The definition offered by Salminen may, in fact, be more appropriate: “microbial cell preparations or components of microbial cells that have a beneficial effect on the health and well-being of the host.”108 These newer microbial preparations may provide alternatives to administering live organisms to ill, immunocompromised preterm infants while allowing for more precise delivery and dosing, and less likelihood of permanently manipulating the intestinal ecosystem and its resultant unknown long-term consequences.
Probiotics: Role in Pathophysiology and Prevention in Necrotizing Enterocolitis, Camilia R. Martin, MD,* and W. Allan Walker, MD, j.semperi. 2008. 01.006

The use of probiotics to enhance intestinal health has been proposed for many years. Probiotics are traditionally defined as viable microorganisms that have a beneficial effect in the prevention and treatment of specific pathologic conditions when they are ingested. There is a relatively large volume of literature that supports the use of probiotics to prevent or treat intestinal disorders. However, the scientific basis of probiotic use has been firmly established only recently, and sound clinical studies have begun to be published. Currently, the best-studied probiotics are the lactic acid bacteria, particularly Lactobacillus sp. and Bifidobacterium sp. However, other organisms used as probiotics in humans include Escherichia coli, Streptococcus sp., Enterococcus sp., Bacteroides sp., Bacillus sp., Propionibacterium sp. and various fungi. Some probiotic preparations contain mixtures of more than one bacterial strain. Probiotics have been examined for their effectiveness in the prevention and treatment of a diverse spectrum of gastrointestinal disorders such as antibiotic-associated diarrhea (including Clostridium difficile–associated intestinal disease), infectious bacterial and viral diarrhea (including diarrhea caused by rotavirus, Shigella, Salmonella, enterotoxigenic E. coli, Vibrio cholerae and human immunodeficiency virus/ acquired immunodeficiency disorder, enteral feeding diarrhea, Helicobacter pylori gastroenteritis, sucrase maltase deficiency, inflammatory bowel disease, irritable bowel syndrome, small bowel bacterial overgrowth and lactose intolerance. Probiotics have been found to inhibit intestinal bacterial enzymes involved in the synthesis of colonic carcinogens. There are many mechanisms by which probiotics enhance intestinal health, including stimulation of immunity, competition for limited nutrients, inhibition of epithelial and mucosal adherence, inhibition of epithelial invasion and production of antimicrobial substances. Probiotics represent an exciting prophylactic and therapeutic advance, although additional investigations must be undertaken before their role in intestinal health can be delineated clearly.
The Role of Probiotic Cultures in the Control of Gastrointestinal Health, Rial D. Rolfe - Symposium: Probiotic Bacteria: Implications for Human Health, 2000 American Society for Nutritional Sciences.

Abstract
Aims : To determine the mechanism of action of antimicrobial protein, lactosporin, against Gardnerella vaginalis and to evaluate its safety in-vitro.
Methods and Results — Bacillus coagulans ATCC 7050 was grown at 37 °C for 18 hours. The cell free supernatant was concentrated 10-fold and screened for antimicrobial activity against indicator strain Micrococcus luteus. The mode of action of lactosporin was determined by measuring the potassium release and monitoring the changes in transmembrane potential (Δψ) and transmembrane pH (ΔpH) of the sensitive cells. Lactosporin caused efflux of potassium ions from M. luteus cells and dissipation of ΔpH in G. vaginalis while it had no effect on the Δψ. The safety of lactosporin was evaluated by using EpiVaginal™ ectocervical (VEC-100) tissue model. Over 80% of the cells in the vaginal tissue remained viable after exposure to lactosporin for 24 hours.
Conclusions — Lactosporin potentially exerts its antimicrobial activity by selective dissipation of ΔpH and/or by causing leakage of ions from the sensitive cells. Safety studies suggest that lactosporin is a non-cytotoxix antimicrobial for vaginal application.
Significance and Impact of the Study—This study revealed that lactosporin is an effective and safe antimicrobial preparation with potential application for control of bacterial vaginosis.
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Study for LactoSporin [SBLACTSPORIN]