Diverse Bioactive Molecules from the Genus <em>Lactobacillus</em>

Rodney H. Perez; Amily E. Ancuelo

doi:10.5772/intechopen.102747

Abstract

Lactobacilli are widespread microorganisms and are broadly employed in a variety of applications. It is one of the LAB genera that has been designated as Generally Regarded as Safe (GRAS) and many of its member species are included in the Qualified Presumption of Safety (QPS) list. Lactobacillus is commonly utilized as a starter culture in many fermented food products, probiotics, and has long been used as natural bio-preservatives to increase shelf life and improve food quality and safety. Aside from the many benefits, it delivers in the food sector, the use of lactobacillus strains in the clinical setting as a prophylactic and/or treatment for a variety of diseases has gained increasing attention. These uses of lactobacillus are all made possible through the diverse bioactive molecules it generates. Lactobacillus exerts its positive health and nutritional effects through a variety of mechanisms, including inhibition of pathogen adhesion or colonization, metabolic activity through the synthesis of metabolites and enzymes, and immune system modulation among others. The ability of many lactobacillus strains to mediate the bio-conversion of certain metabolites has also been shown in numerous studies. This chapter describes the recent findings on the impact of the diverse bioactive molecules produced by different lactobacillus strains, their mode of action, and their application in different industries.

Keywords

lactic acid bacteria
GRAS
lactobacillus
bioactive compounds
probiotics

Author Information

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Rodney H. Perez*
- National Institute of Molecular Biology and Biotechnology (BIOTECH), University of the Philippines Los Baños (UPLB), Laguna, Philippines
Amily E. Ancuelo
- National Institute of Molecular Biology and Biotechnology (BIOTECH), University of the Philippines Los Baños (UPLB), Laguna, Philippines

*Address all correspondence to: rhperez@up.edu.ph

1. Introduction

One of the most significant, and extensively used lactic acid bacteria (LAB) is lactobacillus. This genus comprises a large number of species that can be found in diverse environments, such as in plants, food products, and mucosal surfaces of the human body. Lactobacilli are characterized by the formation of lactic acid as the primary end product of carbohydrate metabolism. Species of lactobacillus are Gram-positive, homofermentative, thermophilic, and non-spore-forming rods. Lactobacillus species ferment a broad array of carbohydrates and can ferment extracellular fructans, starch, or glycogen depending on the strain. All organisms formerly assigned to the Lactobacillus delbrueckii group are now included in the emended description of the genus [1].

Among LAB, lactobacillus is one of the genera considered as Generally Regarded as Safe (GRAS) by the U.S. Food and Drug Administration (FDA) as they are a safe means to generate products for a variety of industries. The European Food Safety Authority (EFSA) also grants Qualified Presumption of Safety (QPS) status to many lactobacillus species. The EFSA notes that some LAB strains are susceptible to acquiring virulence and antibiotic resistance genes and have opportunistic properties and hence excluded in the QPS list [2]. Lactobacilli are broadly applied in the food industry as both technical starters in fermented goods and probiotics due to their unique health and nutritional benefits [3, 4]. These microorganisms play an indispensable role in many foods fermentation. For instance, many lactobacilli species have been identified as primary microorganisms in sauerkraut fermentation [5]. Lactobacilli also play a significant part in malolactic fermentation, critical in winemaking [6]. In Chinese Maotai-flavored liquor production, lactobacillus accelerates flavor component conversion from alcohol (ethanol) to acid (lactic acid and acetic acid) [7]. Lactic acid fermentation using L. plantarum was found optimal in improving pea protein isolates aroma and taste [8]. Fermentation with lactobacillus also improved the foaming capabilities of egg white [9]. Many lactobacillus strains are also important in the manufacture of many fermented meat and meat products. Moreover, probiotic lactobacillus was given special attention as well for its ability to stimulate or modulate the immune system [10]. It also has possible applications in health-related areas such as intestinal inflammation [11], prevention of urinary tract infection [12], and treatment against cancer cells [13].

Indigenous LAB is constantly exposed to extreme conditions such as varying temperature, pH, and nutrient levels [14]. As a result, native LAB has been linked to higher competitive metabolic capacities, which encourage their growth as a competitive microbiota for other microorganisms in their natural habitat. The synthesis of a large number of bioactive metabolites is one of these capacities. Among LAB genera, lactobacilli are known producers of diverse bioactive molecules that offer a wide range of benefits to food, agricultural, industrial and clinical fields. They have long been exploited in food and animal feed as natural preservatives. Their antimicrobial action is mostly due to the production of organic acids, hydrogen peroxide, inhibitory compounds, as well as competition for nutrients and the development of antimicrobial compounds like bacteriocin [15]. Several studies have shown that the organic acids produced by lactobacillus like lactic acid kill pathogens at sufficient concentrations, such as Campylobacter jejuni by disrupting its membrane [16]. It also secretes ethanol and fatty acid as antimicrobial molecules. It can produce acetic acid, formic acid, and other acids [17].

Lactobacilli exhibit their beneficial properties through a wide range of processes that include a large spectrum of bioactive compounds. In this chapter, the utility of these microorganisms and their bioactive compound by-products for the promotion of better health and nutrition are summed up. Lactobacilli and their by-products can be utilized in technology and product development geared towards sustainable approaches for the improvement of human conditions targeted by the United Nations 2030 Agenda and its Sustainable Development Goals. The well-established functions of lactobacilli and their bioactive molecules in food fermentation could play a key role in ensuring that people around the world have access to safe and nutritious food by improving the current food production, safety, and preservation. Its application in the clinical setting also has the potential to address major health concerns, including sexual, reproductive, newborn, and environmental diseases which will be discussed in the following sections. Thus, this chapter will center the attention on the different bioactive molecules from the genus lactobacillus, such as bacteriocins, bioactive peptides, SCFAs, vitamins, enzymes, EPs, immune-modulating compounds, bio-converted molecules, and its probiotic properties.

2. Bioactive compounds produced by lactobacillus

2.1 Bacteriocins

Bacteriocins are multifunctional, ribosomal-synthesized antimicrobial peptides. The bactericidal activity of bacteriocins is demonstrated against species that are closely related to the producer strain [18]. The bactericidal or bacteriostatic actions of bacteriocins produced by Gram-positive bacteria, including LAB, are mostly against Gram-positive bacteria including food-borne pathogens [19]. Bacteriocins inhibit their target cells by destabilizing the bacterial cell membrane and/or creating pores resulting in the death of the target cells through a fast-acting mode of action that is active even at very low concentrations [18]. Bacteriocins from Gram-positive bacteria are divided into three classes based on their structural and physicochemical properties: class I (lantibiotics), which are lanthionine-containing peptides; class II, comprise the non-lanthionine-containing bacteriocins [20].

The promise of bacteriocins, particularly from lactic acid bacteria, for various applications has instigated a great deal of interest in bacteriocin research. LAB bacteriocins are recognized for their activity over a wide pH range and are inherently tolerant to extreme thermal stress. The fact that these antimicrobial peptides are colorless, odorless, and tasteless, adds to their potential uses [18]. Bacteriocins also offer a number of advantages over traditional antibiotics. The most notable of which is that they are primary metabolites with relatively straightforward biosynthetic processes compared to conventional antibiotics, which are secondary metabolites. Thus, bioengineering may readily improve their activity or specificity towards their target bacteria [18].

Lactobacillus, is a LAB genus that has been shown to produce diverse bacteriocins (Table 1). A lactobacillus strain isolated from traditional Egyptian dairy products showed antimicrobial actions against different Gram-positive and Gram-negative bacteria [35]. The highest inhibitory activity of L. brevis (B23) was exhibited against Escherichia coli, Staphylococcus and Bacillus.

Class	Bacteriocin	Lactobacillus strain	Reference
I	Paraplantaricin TC318	L. paraplantarum OSY-TC318	[21]
	Plantaricin C	L. plantarum LL441	[22]
	Lactocin S	L. sakei L45	[23]
IIa	Plantaricin 423	L. plantarum 423	[24]
	Plantaricin LPL-1	L. plantarum LPL-1	[25]
	Rhamnocin 519	L. rhamnosus CJNU 0519	[26]
IIb	Gassericin S	L. gasseri LA327	[27]
	Gassericin T	L. gasseri LA327	[27]
	Gassericin M	L. gasseri LM19	[28]
IIc	Acidocin B	L. acidophilus M46	[29]
	Plantaricyclin A	L. plantarum NI326	[30]
	Plantacyclin B21AG	L. plantarum WCFS1	[31]
IId	Sakacin D98a	L. sakei D98	[32]
	Sakacin D98c	L. sakei D98	[32]
	Bactofencin A	L. salivarus DPC6502	[33]
III	Helveticin-M	L. crispatus	[34]

Table 1.

Diverse bacteriocins produced by various strains of Lactobacillus.

A lactobacillus strain has also been described to produce multiple bacteriocins. Lactobacillus sakei 5 from malted barley was found to produce three bacteriocins [36]. Genetic and functional analysis revealed that this strain generates a plasmid-encoded bacteriocin sakacin P, as well as two novels, chromosomally encoded bacteriocins, sakacin T and sakacin X. This strain may be a viable candidate for usage in the brewing sector since it inhibits bacterial strains known to cause severe spoiling problems in this industry.

A strain isolated from human breast milk, Lactobacillus gasseri LM19, was also found to produce several bacteriocins, including a novel bacteriocin, gassericin M [28]. In a complex environment that mimicked human colon circumstances, L. gasseri LM19 not only survived but also expressed seven bacteriocin genes and generated short-chain fatty acids. The gut origin of L. gasseri LM19 enabled it to thrive in GI tract conditions and display antagonistic properties against other gut bacteria, such as enteropathogens [28]. Different bacteriocin-producing L. plantarum strains have also been found in a variety of foods, including meat [37], fermented milk [38], cheese [39], and sourdough [40].

Aside from its usefulness in the food industry, bacteriocin-producing lactobacillus was also investigated for its use in the clinical setting, particularly in preventing and treating vaginal disorders. Lactobacillus is bacteria naturally found in the healthy human vagina [41] and urethra [42]. A low count of lactobacillus is inversely related to high numbers of E. coli in the vagina and a history of recurrent urinary tract infection [43]. A new bacteriocin generated by L. acidophilus KS400 was identified and characterized, as well as its antimicrobial properties against urogenital pathogens [44]. These species have been shown to colonize the epithelial surface and release antimicrobial compounds that regulate the vaginal microflora.

2.2 Bioactive peptides

Digestive proteases and peptidases from human’s release food-encrypted bioactive peptides that can be absorbed by the gut and then reach peripheral organs. However, the enzymatic activity of LAB largely contributes to their release, either into the food matrix or in the gut. Due to the limited length of the overall genome, the biosynthetic abilities of LAB are very limited especially in amino acid synthesis [45]. Therefore, LAB evolved a complex and sophisticated proteolytic system allowing them to get amino acids from the proteins present in the external environment [46]. The proteolytic system of LAB converts protein substrates into free amino acids and small peptides, which enables them to carry out their intrinsic physiological mechanisms such as regulation of intracellular pH, production of metabolic energy, stress tolerance, and biosynthesis of proteins [47].

Numerous bioactive peptides lack activity when protein is encrypted, but display their interesting biological functions when released proteolytically. They have been shown to hold health-promoting qualities as antimicrobials, hypocholesterolemic, opioid antagonists, angiotensin-converting enzyme inhibitors, anti-thrombotic, immuno-modulators, cytomodulators, and antioxidants [48]. The utilization of LAB such as lactobacillus in the synthesis and valorization of new bioactive peptides is a useful method. The proteolytic activity of lactobacillus is strain- and species-dependent: each species has a distinct proteinase composition, encompassing a wide range of proteolytic activities [49].

Over the past years, lactobacillus species have presented great potential as producers of bioactive peptides through fermentation using different protein matrices (Table 2). LAB proteolytic system is capable of producing bioactive peptides from a variety of food proteins, particularly casein, which is the major nitrogen source in their environment. [59]. L. helveticus CICC6024 was employed to effectively ferment milk-casein under fixed fermentation processes to facilitate an efficient bioactive peptide synthesis [60].

Lactobacillus strain	Bioactive peptides	Protein Source	Reference
L. casei	Antihypertensive peptides	Milk	[50]
L. casei	Antimicrobial, antioxidant and ACE-inhibitory peptides	Whey and skim milk	[51]
L. plantarum
L. rhamnosus
L. helveticus	Antioxidative, opioid, stimulating, hypotensive, immunomodulating, antibacterial, and antithrombotic peptides	κ-casein	[52]
L. helveticus	ACE-inhibitory peptides	Milk	[53]
L. helveticus R0389	ACE-inhibitory and immunomodulating peptides	Casein	[54]
L. rhamnosus R0011	ACE-inhibitory and immunomodulating peptides	Casein	[54]
Lactobacillus GG	Immunostimulatory, opioid, and ACE-inhibitory peptides	UHT Milk	[55]
L. plantarum 55	Anti-inflammatory, antihemolytic, antioxidant, antimutagenic, and antimicrobial peptides	Milk	[56]
L. plantarum C2	Anti-oxidant and ACE-inhibitory peptides	Soy milk	[57]
L. sanfranciscensis I4	Anti-oxidant and anti-inflammatory peptides	Italian sourdough	[58]
L. farciminis A19
L. rossiae A20

Table 2.

Bioactive peptides generated by Lactobacillus using different protein matrices.

Other lactobacillus strains have also been found to be capable of releasing bioactive peptides from food proteins. Milk inoculated with L. helveticus and casein hydrolysates generated by L. helveticus CP790 extracellular proteinase both contain antihypertensive peptides [61]. Antihypertensive substances were also recovered from an L. casei cell extract used in fermented milk production [50]. Two fermented kinds of milk containing ACE-inhibitory peptides were generated using L. delbrueckii subsp. bulgaricus and Lactococcus lactis subsp. cremoris strains [62]. Bioactive peptides have been discovered in UHT milk fermented by the probiotic Lactobacillus GG strain and digested by pepsin and trypsin enzymes. These bioactive peptides exhibit varying degrees of immunostimulatory, opioid, and ACE-inhibitory properties [55]. Cultures of L. plantarum, L. casei, and L. rhamnosus from a fecal sample of a human infant were employed as a proteolytic starter culture for the fermentation of skim milk and whey to release small peptides that have antimicrobial, antioxidant, and ACE inhibitory activities. These encrypted bioactive peptides can be utilized as a functional food and/or, dietary supplement, to provide particular health advantages.

Single-activity milk-derived bioactive peptides have been widely reported. The anti-inflammatory, antihemolytic, antioxidant, antimutagenic, and antimicrobial activities of crude extracts and peptide fractions obtained from fermented milk with specific L. plantarum strains were assessed [56]. L. plantarum 55 was found to generate encrypted peptides with extensive capabilities as dietary bioactive components for the development of nutraceutical biotechnological products.

2.3 Short-chain fatty acids (SCFAs)

The small and large intestines of humans lack several carbohydrate-digesting enzymes that can be produced by probiotic bacteria. However, the probiotic bacteria ferment these undigested carbohydrates and produce energy that is utilized by the host to carry out various functions. The undigested sugars are converted into short-chain fatty acids (SCFAs) such as butyrate, acetate, and propionate. The typical reaction of SCFAs production and overall stoichiometry has been summarized and is shown as follows [63]:

59 C6H12O6+38 H2O→60 CH3COOH+18 CH3CH2CH2COOH +22 CH3CH2COOH+96 CO2+134 H2+HeatE1

SCFAs from lactobacillus have been proven to have therapeutic effects against several diseases through their antimicrobial potential (Table 3). For example, L. reuteri produces SCFAs to inhibit colon cancer cell proliferation [69]. Several L. reuteri strains were shown to synthesize SCFAs and demonstrated growth inhibitory activity against colorectal cancer cells. Thus, the anti-cancer action and the ability to generate anti-carcinogenic active substances of L. reuteri indicate that it may be used as a bio-therapeutic. Moreover, the impact of L. paracasei CNCM I-1572 on clinical and gut microbiota-related parameters in irritable bowel syndrome (IBS) was also investigated [65]. L. paracasei CNCM I-1572 was shown to regulate the structure and function of gut microbiota and decrease immunological activation in IBS by substantially increasing the SCFAs acetate and butyrate and a corresponding decrease in the pro-inflammatory cytokine interleukin-15. Several lactobacillus strains were also investigated for their application to treat bacterial vaginosis [64]. The strain L. plantarum ZX27 was found to produce more short-chain fatty acids and lactic acid and inhibited Gardnerella vaginalis growth and adherence.

Lactobacillus strain	SCFA	Spectrum	Reference
L. delbrueckii DM8909	Acetatic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, and isovaleric acid	Gardnerella vaginalis	[64]
L. plantarum ATCC14917
L. plantarum ZX27
L. paracasei CNCM I-1572	Acetatic acid and butyric acid	Ruminococcus bromii and Ruminococcus callidus	[65]
L. paracasei subsp. paracasei NTU 101	Acetic acid, propionic acid, and butyric acid	Clostridium perfringens and Enterobacteriaceae	[66]
L. plantarum G72	Formic acid, acetic acid, propionic acid, and butyric acid	Listeria monocytogenes, Salmonella typhimurium, E. coli, and S. aureus	[67]
L. rhamnosus	Acetic acid, propionic acid	E. coli	[68]
L. reuteri NCIMB -11,951, −701,359, −701,089, −702,655, and − 702,656	Acetic acid, propionic acid, and butyric acid	Caco-2 colon cancer cells	[69]
L. salivarius ssp. salicinius JCM 1230	Propionic acid, and butyric acid	Salmonella	[70]
L. agilis JCM 1048	Propionic acid, and butyric acid	Salmonella	[70]

Table 3.

Antimicrobial spectrum of the SCFAs produced by Lactobacillus strain.

SCFAs are generated by bacteria in the gastrointestinal system, which relies on non-digestible carbohydrates for energy. SCFA production is necessary to increase the acidity of the gut environment, which inhibits many harmful microorganisms. Production of SCFAs has been shown as one mechanism of lactobacillus strains to inhibit the development of metabolic syndrome by its influence on microbiota modulation [71]. The production of SCFAs and antimicrobial activity of L. plantarum G72 for its potential application in improving the diet of pregnant women.

2.4 Vitamins

Vitamins are essential micronutrients that are required for the metabolism of every organism. Humans are incapable of producing vitamins, resulting in vitamin deficiencies, malnutrition, and stunted growth from infants to the elderly. Thus, they must be acquired exogenously (i.e., in the form of diet). All vitamins can be classified into two groups: water-soluble vitamins and fat-soluble vitamins. Water-soluble B-group vitamins are generated by several bacteria and are consumed in the gut. Fat-soluble vitamins, on the other hand, are taken in the digestive tract using lipids as micelles. Plants and animals are natural providers of vitamins, although certain vitamins are chemically produced.

Lactic acid bacteria, especially lactobacillus, are known to be good producers of vitamins. Lactobacillus decreases the overall growth of bacteria-caused diseases by generating these nutritional components (Table 4). Lactobacillus strains from traditional yogurt were able to produce B-group vitamins [73]. L. paracasei subsp. tolerance JCM 1171 (T), L. acidophilus KU, and L. fermentum showed the highest amount of Vitamin B₆ and B₉, B₃, and B₂, respectively. L. plantarum LZ95 originally from infant feces and CY2 from fresh milk were identified to be capable of producing a high level of extracellular vitamin B₁₂ as well [75]. Moreover, co-fermentation of glycerol and fructose in soy-yogurt by L. reuteri has been demonstrated to enhance vitamin B₁₂ synthesis [77].

Lactobacillus strain	Vitamins	Reference
L. fermentum KGL2	Vitamin B₂, B₉, and B₁₂	[72]
L. plantarum KGL3A
L. fermentum KGL4
L. rhamnosus RNS4
L. fermentum WTS4
L. paracasei subsp. tolerance JCM 1171^T	Vitamin B₂, B₃, B₆, and B₉	[73]
L. acidophilus KU
L. fermentum
L. plantarum CRL2130	Vitamin B₂	[74]
L. plantarum LZ227	Vitamin B₂ and B₉
L. plantarum LZ95	Vitamin B₁₂ (adenosylcobalamin and methylcobalamin)	[75]
L. plantarum CY2	Vitamin B₁₂ (adenosylcobalamin and methylcobalamin)	[75]
L. plantarum BHM10	Vitamin B₁₂	[76]
L. plantarum BCF20	Vitamin B₁₂	[76]
L. reuteri	Vitamin B₁₂	[77]
L. rossiae DSM 15814^T	Vitamin B₁₂	[78]

Table 4.

Example of Lactobacillus strains known to produce vitamins.

Some vitamins, particularly riboflavin and folate derivatives, have been shown to help combat certain diseases. Vitamin-producing lactic acid bacteria, particularly strains that produce folate and riboflavin in combination with immune-stimulating strains, could be used as effective alternative types of treatment in patients suffering from a variety of inflammatory diseases [79]. Riboflavin-producing L. plantarum CRL2130, through oral administration, exhibited its ability to prevent trinitrobenzene sulfonic acid-induced colitis in mice, reducing pro-inflammatory cytokines [74].

2.5 Enzymes

Lactic acid bacteria perform metabolic processes due to the synthesis of enzymes. Enzymes play a critical role in biological reactions by acting as biocatalysts, mediating all anabolic and catabolic pathways, and lowering the activation energy of biochemical reactions. The digestive enzymes in the lysosomes, for example, enhance the digestion of a wide range of substances absorbed from outside the cell in the gastrointestinal tract (GIT). These enzymes work together to convert carbohydrates, proteins, and lipids into monomers that can be absorbed by human cells. Examples of digestive enzymes include amylase, lactase, pepsin, trypsin, pancreatic amylase, lipase, nuclease, maltase, and lactase [80].

Lactobacillus strains are well-known enzyme producers (Table 5). Amylases are one of the most often utilized enzymes in industry. These enzymes hydrolyze starch molecules into polymers made up of glucose units [90]. Lactobacillus amylases are considered safe since they are non-pathogenic and the end product of their fermentation is lactate, a commonly utilized flavoring ingredient in the food industry [91]. Several lactobacillus strains such as L. brevis, L. casei, and L. fermentum, were shown to produce a significant quantity of amylase [81]. The amylolytic potential of lactobacillus strains from wet-milled cereals, cassava flour, and fruits has been studied. L. plantarum (AMZ5) showed amylolytic potential through starch hydrolysis as it exhibited remarkable starch degradation capacity. [92].

Lactobacillus strain	Enzymes	Reference
L. brevis	Amylase	[81]
L. fermentum	Amylase	[81]
L. brevis C10CpSA3b6	β-glucanase	[82]
L. crispatus I12pSA3b6
L. brevis I23pSA3b6
L. fermentum I25pSA3b6
L. brevis I211pSA3b6
L. brevis I218pSA3b6
L. bulgaricus	β-galactosidase enzyme	[83]
L. casei	Amylase and invertase	[81]
L. casei LFTI® L26	ACE-inhibitory enzyme	[84]
Lactobacillus delbrueckii QS306	ACE-inhibitory enzyme	[85]
L. helveticus IMAU80872, IMAU80852, and IMAU80851	ACE-inhibitory enzyme	[86]
L. plantarum	α-galactosidase enzyme	[87]
Lactobacillus rhamnosus	β-galactosidase enzyme	[88]
Lactobacillus sp. G3_4_1TO2	Amylase	[89]

Table 5.

Example of enzyme-producing Lactobacillus strains.

Angiotensin-converting enzyme (ACE, EC 33.4.15.1, CD143) has a significant impact on the regulation of arterial blood pressure [93]. Inhibiting this enzyme can cause antihypertensive effects. Because of its role in the renin-angiotensin and kinin-nitric oxide systems, ACE-inhibitors are an ideal physiological target for clinical hypertension treatment [86]. However, ACE inhibitors that are currently available are synthetic pharmacological medicines that are not recommended for usage in healthy or low-risk populations due to side effects such as dry cough, skin rashes, and angioneurotic edema. As a result, producing safe and natural ACE inhibitors is critical for future hypertension therapy and prevention [94]. Previous studies show that ACE inhibitors are already been isolated from different products such as milk [95], cheese [96], yogurt [84], and other dairy products. The L. helveticus strains IMAU80872, IMAU80852, and IMAU80851 from fermented milk possessed a high ACE-inhibitory activity [86]. ACE inhibitory peptides were also isolated and identified from milk fermented with L. delbrueckii QS306 [85]. Moreover, ACE-inhibitory peptides account for the majority of bioactive peptides generated during yogurt fermentation processes. A strong link between L. casei LFTI® L26 growth and ACE inhibition in all yogurt samples was discovered during the initial stages of storage, compared to control yogurt, which reduced substantially after storage [84]. These previous researches prove that bioactive ACE-inhibitory producing lactobacillus strains have a great deal of potential for the improvement and production of functional dairy food products with antihypertensive effects.

The β-galactosidase enzyme, one of the glycosidases, is widely used in the dairy industry as well. These are produced by most lactobacillus species. Lactose, the primary carbohydrate in milk, is hydrolyzed by this enzyme into glucose and galactose, which may be absorbed via the intestinal epithelium. β-galactosidase involves two enzymatic activities: one hydrolyzes lactose and also cleaves cellobiose, cellotriose, cellotetrose, and to some extent cellulose, while the other splits β-glycosides [97]. High β-galactosidase activity observed in L. rhamnosus [88] and L. bulgaricus [83] has also been reported.

2.6 Exopolysaccharides (EPs)

Exopolysaccharides (EPs) are high–molecular, long-chain linear biopolymers containing side chains of homopolysaccharide or heteropolysaccharide carbohydrate units linked with α-glycosidic and β-glycosidic bonds [98]. The enzymes such as glycosyltransferase and glycoside hydrolase convert the sugar nucleotide precursors into EPs. EPs are “food-grade biopolymers,” or extracellular biopolymers with a high molecular weight that are acquired from natural sources and produced during the metabolism of microorganisms [99].

Lactobacillus is one of the species of LAB that is frequently regarded as EPs-producing microorganisms (Table 6). An EPs termed as LPC-1 from L. plantarum C88 showed strong antioxidant activity and exhibited strong hydroxyl radical scavenging activity [107]. A novel EPs was also isolated from L. plantarum KX041 culture from a traditional Chinese pickle juice sample [109]. The EPs had a molecular weight of 38.67 KDa, which exhibited high thermal stability. EPS generated by L. plantarum has a good prospect to be utilized as natural antioxidants or functional additives in the food sector.

Lactobacillus strain	Exopolysaccharide	Reference
L. delbrueckii ssp. bulgaricus SRFM-1	Glucose and galactose	[100]
L. gasseri FR4	Glucose, mannose, galactose, rhamnose and fucose	[101]
L. helveticus MB2–1	Glucose, mannose, galactose, rhamnose, and arabinose (c-EPS)	[102]
L. kefiri MSR101	Galactose and glucose (MSR101)	[103]
L. mucosae (DPC) 6426	β-glucan	[104]
L. pentosus 14FE	Glucose	[105]
L. pentosus 68FE
L. plantarum 47FE
L. plantarum 301102S	Glucose and mannose	[106]
L. plantarum C88	Galactose and glucose (LPC-1)	[107]
L. plantarum H31	Glucose and mannose	[108]
L. plantarum KX041	Arabinose, mannose, glucose, and galactose	[109]

Table 6.

Example of exopolysaccharides produced by Lactobacillus strains.

There has been a growing interest in using EPs-producing LAB for a variety of biological purposes. Among them, the anticancer action of EPs has attracted increasing attention. The EPs produced by L. kefiri MSR101 (MSR101 EPS) and its ability to inhibit the growth of HT-29 colon cancer cells were explored [103]. Structural analysis showed that MRS101 EPS is a heteropolysaccharide having a repeating unit of glucose and galactose and has a partial crystalline nature. In-vitro anticancer tests also showed significant anticancer action of MRS101 EPS against HT-29 cells. Moreover, a novel cell-bound exopolysaccharide (c-EPS) isolated from L. helveticus MB2–1 [102] showed high structural stability and may be used to make films and edible nanostructures for drug and food additive encapsulation. In vitro anticancer testing revealed that c-EPS exhibited substantial anticancer effects against human HepG-2 liver cancer, BGC-823 gastric cancer, and notably HT-29 colon cancer cells.

The utilization of probiotic microorganisms has been linked to a lower risk of cardiovascular disease, the leading cause of mortality and disability. The effect of dietary treatment of exopolysaccharide-producing probiotic lactobacillus on lipid metabolism and gut microbiota was investigated using apolipoprotein E (apoE)–deficient mice [104]. Dietary supplementation with a β-glucan–producing probiotic strain L. mucosae Dairy Product Culture Collection (DPC) 6426 resulted in lipid metabolism regulation in the mouse model of atherosclerosis. Several strains of L. delbrueckii subsp. bulgaricus isolated from homemade yogurt were also shown to produce EPs that can help cholesterol reduction [110]. The cholesterol removal mechanism, which involves binding or adhering to the bacterium cells, particularly to the EPS generated by the bacteria and enclosing the bacterial cells as a capsule, may be useful and relevant in human serum cholesterol management.

2.7 Immune-modulating compounds

Different lactobacillus strains synthesize immune-modulating compounds that confer various health effects (Table 7). These most widely utilized probiotic agents promote intestinal microbiota and gut health and regulate the immune system in consumers. The immune system is modulated by probiotic bacteria, which control the synthesis of antibodies, interleukins, cytokines, and lymphocytes [121]. The probiotic bacteria interact with intestinal epithelial cells and generate immunomodulatory molecules, which activate the host immune response. By stimulating the production of interleukin-10 (IL-10) and immunoglobulin A antibodies (IgA), probiotics regulate immunity and inflammatory gene expression, reducing the host immunological response to infections [122]. IgA production, which is stimulated by dendritic cells, naive T cells, and B cells, promotes immune-modulatory effects as well and helps to eliminate pathogenic bacteria.

Lactobacillus strain	Immune-modulating compound/mechanism	Reference
L. acidophilus DSM 32241	Increase in IgA and IgG levels	[111]
L. helveticus DSM 32242
L. paracasei DSM 32243
L. plantarum DSM 32244
L. brevis DSM 27961
L. brevis B13–2	Activated RAW 264.7 murine macrophages	[112]
L. fermentum BioE LF11	Inhibited secretion of lipopolysaccharide-induced pro-inflammatory cytokines IL-6 and TNF-α in RAW264.7 macrophages in vitro	[113]
L. plantarum BioE LPL59
L. paracasei BioE LP08
L. fermentum CECT5716	Modulation of intestinal cytokines IL-10 and IL-12	[114]
L. fermentum JDFM216	Increased sIgA	[115]
L. gasseri	Increased IFN-levels	[116]
L. fermentum
L. plantarum
L. paracasei subsp. paracasei G15	Lowered circulating LPS and inflammation cytokines, such as IL-1β and IL-8, and alleviated the inflammatory status and islet β-cell dysfunction	[117]
L. casei Q14		[117]
L. paracasei KBL382	Increased IL-10 and growth factor-β	[118]
L. plantarum ST-III	Decrease the number of inflammatory cells	[119]
L. rhamnosus GR-1	TLR4	[120]

Table 7.

Immune-modulating compound/mechanism by Lactobacillus.

Numerous uropathogenic bacteria can interfere with the ability of the host to eliminate pathogens by subverting cellular functions. Probiotic L. rhamnosus GR-1 affected the immunological response of E. coli challenged of bladder cells by increasing NF-kappaB activation and TNF release [120]. The urogenital probiotic L. rhamnosus GR-1 regulated NF-kappaB activation by boosting TLR4 levels on bladder cells and modifying subsequent cytokine release from urothelial cells. These lactobacilli might help pathogen identification and infection control by affecting immunological factors like TLR4, which are crucial in the fight against infections.

Immune modulation and alterations in intestinal microbiota have been associated with probiotic administration, with implications for atopic dermatitis (AD). Oral administration of L. paracasei KBL382 was shown to significantly decrease AD-related skin lesions, epidermal thickening, immunoglobulin E levels in the blood, and immune cell infiltration [118]. Immunomodulatory activity in mice of L. fermentum JDFM216 was also shown to alter gut microbiota composition thus providing the advantage of improved health through better cognition, physiological behavior, and immunity [115].

The probiotic potential of lactic acid bacteria strains isolated from Korean infant feces and Kimchi was also investigated [116]. The production of lymphocyte interferon (IFN) and cell proliferation were measured to assess the immunological modulatory activities of the strains. L. gasseri, L. fermentum, and L. plantarum strains all showed elevated IFN- levels and lymphocyte proliferation. In an in vivo model that assesses the impact of immune modifying lactobacilli on host life span using Caenorhabditis elegans as a model organism, feeding with L. plantarum CJLP133 and L. fermentum LA12 extended the average life span of the model host. Moreover, L. brevis B13–2 induced the expression of numerous cytokines (TNF-, IL-1, and IL-6) and iNOS [112].

2.8 Probiotic properties

Probiotics are live microorganisms that, when given in sufficient amounts, provide health benefits to the host. They create a favorable environment for the proper functioning of different metabolic activities in the gut, such as protein, carbohydrate, vitamin, and enzyme synthesis. Acids and the proteolytic activity of lactic acid bacteria inhibit harmful microorganisms in the intestine [123].

Colonized probiotic bacteria have a wide array of beneficial effects on the host cell, all of which are mediated via a large number of bioactive molecules. One of the mechanisms of probiotics includes competitive inhibition of the harmful bacteria by changing the pH and limiting the availability of oxygen, which leads to a less favorable environment in the intestine [123]. Probiotics also produce specific toxins with relatively narrow killing ranges, such as bacteriocins. It can also manufacture key micronutrients including vitamins, amino acids, and enzymes, boosting dietary nutrient bioavailability. Probiotics play an important role in stimulating the host immune system and enhancing the metabolic activity of carbohydrates as well [124].

Lactobacillus strains are essential components of the human and animal microbiome, and their varied impacts on host health have attracted a lot of interest [125]. Lactobacillus is one of the widely existing probiotic microorganisms. Probiotic lactobacilli have a significant and positive impact on the growth of the host, particularly in terms of enhancing body weight and size. The administration of probiotics L. casei variety rhamnosus to children with acute diarrhea showed a decrease in fecal lactoferrin and calprotectin concentrations and recovered faster as they exhibited significantly better appetite and oral intake, body weight gain, abdominal pain, bloating, and bowel movements [126]. An interleukin-22 (IL22)-secreting L. reuteri was shown to ameliorate non-alcoholic fatty liver disease [127].

2.9 Bio-converted metabolites

Dietary phytochemicals commonly occur in plant-based foods such as fruits and vegetables. These plant components with distinct bioactivities towards animal biochemistry and metabolism are being thoroughly investigated for their potential to deliver health advantages [128]. Phytochemicals often found as glyconjugates have lower bioactivity and bioavailability than their aglycone derivatives, which are smaller and less polar [129]. As a result, deglycosylation of plant glyconjugates (PGs) is recognized as a key factor in modulating their biological activity [130]. An L. acidophilus strain isolated from the human gut can activate dietary-relevant PG [131]. L. acidophilus was able to deglycosylate and externalize salicyl alcohol thus making it available for oxidation to salicylic acid by other microbial strains. This exhibits the ability of Lactobacillus to produce or mediate in the production of bio-converted metabolites (Table 8).

Lactobacillus strain	Bio-converted metabolites	Reference
L. acidophilus NCFM	Salicin	[131]
L. acidophilus	Resveratrol	[131]
L. acidophilus	Resveratrol	[132]
L. casei
L. plantarum
L. delbrueckii	β-maltooligosaccharides of glycitein and daidzein	[133]
L. intestinalis	Equol	[134]
L. kimchi JB301	Resveratrol	[135]
L. mucosae EPI2	Equol	[136]
L. plantarum	Daidzein	[137]
L. sakei subsp. sakei
L. coryniformis
L. plantarum K2–12	Daidzein and genistein	[138]
L. curvatus JD0–31	Daidzein and genistein	[138]
Lactobacillus sp. Niu-O16	S-equol	[139]

Table 8.

Bio-converted metabolites produced by Lactobacillus.

Resveratrol is a phytochemical found naturally in the grape skin and seeds, wine, berries, and medicinal plants [140]. It has antioxidant, anti-inflammatory, immunomodulatory, glycemic and lipid regulating, neuroprotective, and cardiovascular protective characteristics that can help protect against a wide range of chronic diseases [141]. The bioavailability and bioactivity of resveratrol are limited due to its presence in plants in glycosidic form as piceid. To get adequate amount and activity, deglycosylation of piceid to resveratrol from plant sources is necessary. A study by Basholli-Salihu et al. [132]investigated the enzymatic ability of probiotics to transform picied to resveratrol. Cell extracts of several probiotic strains from Bifidobacterium and Lactobacillus spp., including B. infantis, Bifidobacterium bifidum, L. acidophilus, L. casei, and L. plantarum have been shown to efficiently convert piceid to resveratrol. L. acidophilus effectively converts polydatin to resveratrol as well [131].

L. mucosae EPI2 was shown to convert daidzein to equol. Daidzein is a naturally occurring isoflavone but has lesser bioactivity than its deglycosylated form equol. Equol has significantly stronger estrogenic than daidzein [136]. Bovine rumen strain Lactobacillus sp. Niu-O16, in a mixed culture with human intestinal strain Eggerthella sp. Julong 732, has also been proven to successfully synthesize S-equol from daidzein through dihydrodaidzein under anaerobic conditions [139]. High amounts of equol have been shown to efficiently lower the risk of cancer.

3. Conclusion

This chapter summarizes the current knowledge of the existence of diverse bioactive molecules produced by the genus lactobacillus. The diverse bioactive compounds synthesized by lactobacillus confer health and nutritional benefits to humans and animals. These compounds include bacteriocin, bioactive peptides, short-chain fatty acids, vitamins, enzymes, exopolysaccharides immune-modulating compounds, and bio-converted molecules. Collectively, the physiological function and health of the consumers are enhanced and improved by these molecules.

Conflict of interest

The authors declare no conflict of interest.

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Diverse Bioactive Molecules from the Genus Lactobacillus

Lactobacillus - A Multifunctional Genus

Abstract

Keywords

Author Information

Rodney H. Perez*

Amily E. Ancuelo

1. Introduction

2. Bioactive compounds produced by lactobacillus

2.1 Bacteriocins

Table 1.

2.2 Bioactive peptides

Table 2.

2.3 Short-chain fatty acids (SCFAs)

Table 3.

2.4 Vitamins

Table 4.

2.5 Enzymes

Table 5.

2.6 Exopolysaccharides (EPs)

Table 6.

2.7 Immune-modulating compounds

Table 7.

2.8 Probiotic properties

2.9 Bio-converted metabolites

Table 8.

3. Conclusion

Conflict of interest

References

Bacteriocins: Applications in Food Preservation and Therapeutics

Diverse Bioactive Molecules from the Genus Lactobacillus

Lactobacillus - A Multifunctional Genus

Abstract

Keywords

Author Information

Rodney H. Perez*

Amily E. Ancuelo

1. Introduction

2. Bioactive compounds produced by lactobacillus

2.1 Bacteriocins

Table 1.

2.2 Bioactive peptides

Table 2.

2.3 Short-chain fatty acids (SCFAs)

Table 3.

2.4 Vitamins

Table 4.

2.5 Enzymes

Table 5.

2.6 Exopolysaccharides (EPs)

Table 6.

2.7 Immune-modulating compounds

Table 7.

2.8 Probiotic properties

2.9 Bio-converted metabolites

Table 8.

3. Conclusion

Conflict of interest

References

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Lactobacillus