Therapeutic Properties of Lactic Acid Bacteria

Introduction

Lactic acid bacteria (LAB) play a multifaceted role in the food, agricultural, clinical, and pharmaceutical industries. The bacteria’s different nutritional, environmental, and advanced adhesion adaptive properties enable them to grow easily in other environments, such as fermented dairy products, meat, fish, fruit, vegetable, and cereal products. Moreover, LAB is a common inhabitant of human mucosal surfaces, including the oral cavity, vagina, and gastrointestinal tract (GIT) [1, 2]. The region between the duodenum and the terminal ileum is the primary site colonized by LAB species such as Lactobacillus. This area is covered with a layer of mucus composed mainly of mucin-type glycoproteins [3]. Probiotic L. rhamnosus GG can remain in the intestine long by adhering to mucus, thanks to its strain-specific pili [4].

Microorganisms with phylogenetic, genomic and metabolic variations can colonize the digestive system and provide beneficial effects on health. LAB plays an active role in nutrition and host resistance against pathogen microorganisms, in the regulation of the immune system and the maturation of host tissues [5]. Moreover, LAB possesses therapeutic properties that are vital for human health enhancement [1]. Therapeutic agents of LAB can be used in the treatment of autoimmune diseases and protection against cancer [5]. The metabolic activity created by LAB during fermentation positively affects the immunomodulatory activity by changing the structure of herbal medicine components [6].

Recombinant Lactic Acid Bacteria

As a vector carrying prophylactic and therapeutic molecules, LAB can specifically produce, amplify, and deliver the protein of interest orally, intranasally, and vaginally. Moreover, recombinant LAB can be used to deliver functional proteins to these mucosal tissues in the treatment of many different pathologies, such as GIT-related diabetes, cancer, and viral infections [7]. These recombinant LAB, such as Lactococcus lactic and Lactobacillus plantarum, have generated increasing interest as they may provide advantages over different mucosal delivery systems [8]. Mucosal delivery of therapeutic and prophylactic molecules is achieved using LAB. One significant advantage of LAB as a vaccine delivery vehicle is that it delivers therapeutic and prophylactic molecules to mucosal surfaces. It can elicit antigen-specific secretory immunoglobulin A responses at mucosal surfaces [9]. In addition, LAB provides advantages for the production of therapeutic proteins due to their safety status and ability to survive passage through the GIT [10]. Therefore, creating a safe delivery environment of recombinant proteins for the treatment of a wide range of diseases may be a promising alternative [7]. Over the past two decades, the significant health benefits of recombinant LAB administered via the mucosa have been successfully indicated using mostly animal models. However, recently, it has been applied in clinical studies on humans [10]. Additionally, LAB as a live vector precisely replicates, produces and delivers the relevant protein, which can provide a significant reduction in the production cost of therapeutic agents [7]. Lactococcus and Lactobacillus are two crucial LAB genera used to generate recombinant molecules [10]. Moreover, Lactococcus lactis is one of the most commonly used species for cloning and producing recombinant proteins [7].

Developments

Lactobacillus plantarum has been shown to limit colon inflammation and promote oral tolerance induction. Moreover, Lactobacillus fermentum ME-3 has been demonstrated to have antimicrobial activity against intestinal pathogens and high antioxidative activity [11]. A new technology, mini cells and SimCells, can be produced from LAB. These cells can be loaded with a number of different chemotherapeutic drugs in nanosized drug delivery systems with specific ligands that target tumor cells with minimal toxicity to healthy cells. Lactobacillus fermentum, Lactobacillus farciminis, and Lactobacillus rhamnosus were able to produce AgNPs in different sizes of 11.2, 17, and 15.7 nm, respectively [12]. The intestinal system of animals contains a complicated ecosystem in which nutrients, microbiota, and host cells interact highly. Probiotics are part of the natural microbiota in the intestine and play a role in maintaining homeostasis. In livestock and poultry farming, LAB is considered a probiotic due to its curative effects on the health of the host and its important effects in the treatment of animal diseases. For these reasons, they are considered the alternative to antibiotics to advance animal health [13].

Antimicrobial Agents

The treatment of intestinal infections has two purposes: improving clinical symptoms (symptomatic treatment) and eliminating pathogenic microorganisms (etiological antimicrobial therapy). It has been determined that LAB may be effective in eliminating intestinal pathogens [14]. In addition, since LAB produce antimicrobial agents such as bacteriocins that help the biological preservation of food, they function as a strong antagonistic, inhibitory, and antimicrobial defence system against pathogens and spoilage microorganisms. LAB can synthesise bioactive metabolites such as bacteriocins (reuterin, reutericyclin, nisin enterocin pediocin, and lacticin), hydrogen peroxide, pyroglutamic acid, carbon dioxide, acetoin, diacetyl, ethanol, acetaldehyde, antifungal compounds (3-hydroxy fatty acids, propionate, phenyl-lactate, hydroxyphenyl-lactate, and cyclic dipeptides), and organic acids (lactic, acetic, formic, propionic, and butyric acids) as antimicrobial agents [1, 12, 13, 14, 15]. Hydrogen peroxide and antimicrobial peptides are substantial in competitive exclusion and probiotic features [16]. Lactocidin, the bacteriocin of Lactobacillus acidophilus, showed inhibitory effects against many pathogens such as Salmonella, Staphylococcus, Bacillus, Escherichia, Streptococcus and Proteus [15]. Hydrogen peroxide-producing LAB strains can effectively inhibit Staphylococcus aureus and Pseudomonas spp. Hydrogen peroxide, whose antimicrobial effect blocks glycolysis, is active only in the upper part of the GI tract and in the mouth where oxygen is present [16]. Furthermore, LAB generate an anti-inflammatory such as chemoattractants that can prevent lipopolysaccharide-induced production of proinflammatory cytokines in macrophages. L. plantarum A41 and L. fermentum SRK414 together can reduce the levels of inflammation-promoting cytokines such as TNFα, IL1b and IL8 [17].

LAB-metabolites can prevent the growth of spoilage and food-borne pathogenic microorganisms, and they are classified as natural antimicrobial agents [18]. Concerns about antibiotic resistance of important food pathogens and efforts to eliminate or reduce the use of synthetic additives as antimicrobial agents remain. It is of great importance to investigate new effective alternatives to ensure food quality and safety [19].

Conclusion

Natural and synthetic products are used as antimicrobial agents. Although synthetic products impact consumer health, they may raise safety and toxicity concerns. Thus, new natural products, such as metabolites of microorganisms, need to be discovered. Due to its advantages, such as good characterization and short production time, the proteins from which LAB is synthesized are of commercial interest compared to other therapeutic agents [5]. Furthermore, LAB- biosurfactants have broad applications in bioremediation, biodegradation, and the agricultural, cosmetic, and pharmaceutical industries [20]. Biosurfactants provide advantages over other synthetic counterparts due to their biodegradability, low toxicity, structural diversity, and ability to remain stable over a wide range of pH, temperature, and salinity [21].

More studies are needed since therapeutic agents may have different properties from strain to strain. However, LAB has excellent potential for biotechnological studies to solve problems in the medical and food sectors. Future perspectives on LAB studies may relate to discovering new metabolites, combining antibiotics and metabolites, and advances in genetics.