**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*.

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


#### **Table 1.**

*Diverse bacteriocins produced by various strains of* Lactobacillus.

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 *Diverse Bioactive Molecules from the Genus* Lactobacillus *DOI: http://dx.doi.org/10.5772/intechopen.102747*

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].

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].


#### **Table 2.**

*Bioactive peptides generated by* Lactobacillus *using different protein matrices.*

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 shortchain 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]:

$$\begin{array}{c} \text{59}\ \text{C}\_6\text{H}\_{11}\text{O}\_6 + \text{38}\ \text{H}\_2\text{O} \rightarrow \text{60}\ \text{CH}\_3\text{COOH} + \text{18}\ \text{CH}\_3\text{CH}\_2\text{CH}\_2\text{COOH} \\ \text{4-22}\ \text{CH}\_3\text{CH}\_2\text{COOH} + \text{96}\ \text{CO}\_2 + \text{134}\ \text{H}\_2 + \text{Heat} \end{array} \tag{1}$$

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 shortchain fatty acids and lactic acid and inhibited *Gardnerella vaginalis* growth and adherence.

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.


#### **Table 3.**

*Antimicrobial spectrum of the SCFAs produced by* Lactobacillus *strain.*

#### **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].

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


#### **Table 4.**

*Example of* Lactobacillus *strains known to produce vitamins.*

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 *Diverse Bioactive Molecules from the Genus* Lactobacillus *DOI: http://dx.doi.org/10.5772/intechopen.102747*


#### **Table 5.**

*Example of enzyme-producing* Lactobacillus *strains.*

*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].

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 EPsproducing 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.

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.


#### **Table 6.**

*Example of exopolysaccharides produced by* Lactobacillus *strains.*

#### **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.

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].


#### **Table 7.**

*Immune-modulating compound/mechanism by* Lactobacillus.

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**).

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.


**Table 8.**

*Bio-converted metabolites produced by* Lactobacillus.

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.
