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Probiotics are host-compatible microorganisms that can optimally alter the balance of intestinal microflora, inhibit the growth of harmful bacteria, improve digestion, and increase the body\'s resistance by strengthening the immune system. Studies show that probiotics have antioxidant properties. Antioxidants are compounds that reduce the risk of various cancers and diseases. These compounds, in fact, inhibit the activity of free radicals and prevent their oxidation. By inactivation of free radicals, the body cells are protected from the destructive effects of these compounds. Oxidative stress is a condition that occurs as a result of disturbing the antioxidant-prooxidant balance in the cell, which eventually leads to apoptosis and cell death. Consumption of probiotic strains with antioxidant activity can benefit human health by reducing oxidative damage. Since the use of probiotics helps hemostasis, improves immune responses, and prevents many disorders caused by oxidation in the host, in this chapter, we discuss the antioxidant effects of probiotics as functional foods.
National Institute of Genetic Engineering and Biotechnology, Iran
*Address all correspondence to: allahyar@nigeb.ac.ir
1. Introduction
Oxidative stress is a process that leads to an increase in the level of oxygen radicals within the cell, which in turn causes damage to vital macromolecules (such as lipids, proteins, and nucleic acids) in the body [1]. Reactive oxygen species (ROS) are reactive molecules that contain superoxide anion radicals, hydroxyl radicals, and hydrogen peroxide. By contrast, natural antioxidants contain enzymatic antioxidants, such as superoxide dismutase (SOD), glutathione reductase (GR), and glutathione peroxidase (GPx), as well as non-enzymatic antioxidants, such as various types of vitamins, glutathione, and carotenoids, which have been formed during the evolution of organisms to prevent damage caused by oxidative stress [2]. Synthetic antioxidant additives can be used to prevent the oxidation of cellular compounds and thus prevent damage due to oxidative stress. The use of synthetic antioxidants has been questioned due to some reported side effects. Therefore, the preparation and use of natural antioxidants instead of synthetic antioxidants have attracted much attention [3, 4]. Probiotics are non-pathogenic microorganisms so sufficient consumption of them is beneficial for gastrointestinal health [4]. They also show antioxidant properties in various ways [5, 6, 7, 8].
In all animals and plants, maintaining a normal oxygen concentration is essential. In contrast, an imbalance in oxygen concentration will lead to consequences, such as hypoxia (low oxygen) and oxidative stress (high oxygen), which can lead to tissue damage and even cell death. Cigarettes, herbicides, nitrogen oxide, ozone, radiation, and some metals affect oxygen concentration and oxidative stress conditions [9].
ROS originates from the metabolic process of oxygen used to induce oxidative stress [10]. The sources of ROS production are divided into exogenous and endogenous. Vital molecule changes due to reaction with ROS can be associated with various chronic diseases, such as atherosclerosis, osteoarthritis, diabetes, Alzheimer's disease, degenerative neurological diseases, and cardiovascular disease (Figure 1) [11, 12, 13, 14, 15, 16]. ROS concentration determines their role; so that in equilibrium, they can play a role as the second cellular messenger and regulator of biological processes, but an excessive increase of ROS concentration causes oxidative stress [17, 18].
Figure 1.
Reactive oxygen species (ROS) and associated diseases.
In 1991, the relationship between the induction of oxidants (ionizing radiation) and the activation of transcription factors was identified [19]. ROS affects the redox-sensitive elements of some transcription factors, such as hypoxia-inducible factors (HIFs) and kinases like phosphatidylinositol 3-kinase (PI3K); thus, it is possible to regulate these factors by oxygen free radicals [1, 20]. It is not easy to use antioxidants, because the body needs a sufficient concentration of ROS for specific purposes, but antioxidants alter the redox biology and interfere with the body's normal functioning.
According to researches, in metabolic diseases (such as obesity and diabetes), there is an imbalance in the intestinal microbiota, so people's health is associated with the intestinal microbiota. As a result, by balancing the altered microbial flora by consuming some cloning probiotics, the health status of individuals can be improved [21, 22, 23]. In addition, reducing undesirable metabolites and precancerous enzymes and stimulating the immune system (cellular and humoral) are other beneficial effects of probiotics to improve the gastrointestinal status and prevent colorectal cancer [2].
In the pharmaceutical and food industries, lactic acid bacteria (LAB) strains are widely used probiotics [24]. One of the beneficial effects of these probiotics on the body of patients is the improvement of the condition in metabolic diseases [22, 25] and ulcerative colitis (UC) [26, 27, 28]. Also, based on research on fish, improvement of oxidative status and promotion of immunity with probiotics, such as Lactobacillus lactis and Lactobacillus rhamnosus, are observed [29, 30].
Bifidobacteria are an example of another common bacterial probiotic. The beneficial effects of these probiotics include improving women with irritable bowel syndrome [31] and strengthening the immune system against tumors [32]. The presence of characteristics in Bacillus species has made them one of the most widely used probiotics in the food industry. One of these characteristics is the ability to produce protease, amylase, and lipase enzymes [33].
Based on the evidence, LAB strains are resistant to various types of ROS, such as superoxide anions, peroxide radicals, and hydroxyl radicals [34, 35]. Studies in recent decades show the antioxidant potential of probiotics; for example, the probiotic Bifidobacterium animalis 01 eliminates free radicals (such as hydroxyl and anion peroxide) in vitro and increases antioxidant activity in mice [6]. In addition, improving the state of oxidative stress by multivitamin probiotics in people with type 2 diabetes [36] and increasing the level of antioxidants and neutralizing the effects of ROS by Lactobacillus rhamnosus in athletes who expose their bodies to oxidative stress [37]. Some of the studies on the relationship between probiotics and various diseases are listed in Table 1.
Probiotics
Results
References
Lactobacillus plantarum PBS067, Lactobacillus reuteri PBS072 and Lactobacillus rhamnosus LRH020
Improving levels of inflammatory markers in patients with atopic dermatitis.
4. The mechanisms of action of probiotics in antioxidation
There are different types of probiotics, so a variety of resistance mechanisms in different probiotic strains to cope with oxidative stress can be expected (Figure 2).
Figure 2.
The action modes of probiotic bacteria in antioxidation.
4.1 Metal chelating ability
Some probiotics exert their antioxidant potential by preventing metal ions from oxidizing. They use chelators to trap metal ions. These chelators include bathophenanthroline disulfonic acid (BPS), desferrioxamine, and ethylene diamine tetraacetic acid (EDTA) [45].
Different strains of probiotic bacteria were studied for this antioxidant mechanism; for example, among the various strains capable of chelating iron (II) or copper (II), the strains of Lactobacillus casei KCTC 3260 and Streptococcus thermophilus 821 have a much higher ability to chelate iron (II) and copper (II) [46]. Also, the high potency of Lactobacillus helveticus CD6 intracellular cell-free extraction in chelating iron (II) ions can be mentioned [47].
These chelating agents are not fully understood in probiotic bacteria. However, studies have shown their role in inhibiting phosphate ester displacement enzymatic reactions, as well as the production of radicals (such as peroxyl radical and alkoxyl radical) due to the decomposition of hydroperoxide compounds [48].
4.2 Antioxidant enzymes system
Mitochondria are sources of superoxide production. Superoxide is one of the most prevalent ROS. To reduce the risk of this compound, an enzyme called superoxide dismutase (SOD), as one of the essential enzymes in antioxidant enzyme systems, is needed. This enzyme breaks down the high-risk compound superoxide and converts it into less dangerous compounds, such as hydrogen peroxide and water. Therefore, it can be said that SOD in animals and also in prokaryotes plays an important role in regulating ROS [49].
Types of SOD enzymes have been identified in mammals and bacteria, which are used against oxidative stress. Fe-SOD and Mn-SOD have been observed in bacteria [50]; for example, the Mn-SOD in Lactobacillus fermentum E-3 and E-18 was reported by Kalisar et al. [35]. While cytoplasmic and extracellular Zn-SOD and mitochondrial Mn-SOD have been observed in mammals [50].
SOD enzymes need suitable transporters, that can be used in the local delivery of these enzymes [51] because despite its antioxidant activity [52, 53, 54], the limited bioavailability of SOD (due to its short half-life in the circulating) has questioned its therapeutic application. The use of probiotic bacteria for this purpose led to successful results; for example, the use of probiotic bacteria as a transporter for topical delivery of SOD was effective in counteracting the oxidative stress induced by ROS in people with intestinal diseases. Also, according to a study, engineered strains of Lactobacillus casei BL23 (capable of producing SOD) improved the inflammatory status and increased enzymatic activity of mice with Crohn's disease, which shows the beneficial effect of using probiotic bacteria as a carrier [51].
Another enzyme that can be found in probiotic bacteria (except LAB) is called catalase (CAT), Which acts as an antioxidant under oxidative stress. CAT is involved in a reaction known as Fenton. In this reaction, CAT inhibits the production of hydroxyl radicals by the decomposition of hydrogen peroxide, in this way, exerts its antioxidant role [55]. To determine the antioxidant effect of the enzyme CAT, studies have been performed on bacteria that contain this enzyme. CAT-producing probiotic bacteria include Lactococcus lactis and the engineered strains of Lactobacillus casei BL23 [56].
Another action of probiotics inside the host is to enhance antioxidant activity by increasing the levels and activity of several enzymes. For example, according to studies, the probiotic Lactobacillus fermentum increases the levels of SOD, GPx, CAT and Cu, and Zn-SOD enzymes [57], yeast probiotics increase the activity of GPx enzyme [58], and Bacillus amyloliquefaciens SC06 probiotic increases the expression of genes such as CAT and glutathione S-transferase (GST) in the studied animals [7]. In addition, people with type 2 diabetes show increased antioxidant activity by taking the probiotics Lactobacillus acidophilus La5 and Bifidobacterium lactis Bb12, which is due to increased activity of antioxidant enzymes such as SOD and GPx in red blood cells [59].
4.3 Antioxidant metabolites
Probiotics can exert their antioxidant power in other ways, for example, they produce various metabolites with antioxidant properties. These metabolites include glutathione (GSH), butyrate, and folate.
The properties of folate include the acceptance of mono carbon units, its use in various metabolic pathways, and its necessity in DNA synthesis and regeneration, DNA methylation, and cell division [60].
Studies showed an increase in folate levels in the body of rats and humans after treatment with bifidobacteria [61, 62] and an increase in the level of this metabolite and vitamin B12 in people treated with the probiotic Lactobacillus acidophilus La1 [63]. Evidence also showed that patients with type 2 diabetes experience oxidative stress, and in the absence of metabolites, such as folate and vitamin B12, this condition is exacerbated. Therefore, host treatment with these types of probiotics can increase the levels of these antioxidant metabolites in patients [64]. In addition, according to the study, intact cells of Lactobacillus helveticus CD6 producing folate and intracellular cell-free extract of this probiotic have similar antioxidant power [47]. Vitamins, such as vitamin B1, can make cells more resistant to oxidative stress. According to research, consumption of some probiotics can lead to increased absorption of this vitamin in individuals, which helps protect cells against oxidative stress [65, 66, 67].
GSH is another example of a non-enzymatic antioxidant, which is involved in the removal of radicals (such as hydrogen peroxides, hydroxyl radicals, and peroxynitrite). GSH works in conjunction with the selenium-dependent enzyme glutathione peroxidase [68]. Probiotics may contain GSH, and have antioxidant properties under oxidative stress. According to studies, Lactobacillus fermentum E-3, E-18, and ME-3 are among the probiotics with large amounts of GSH [35, 69].
During the fermentation of a series of indigestible substances, the microbiota makes a short-chain fatty acid (SCFA) called butyrate [70]. Butyrate has an antioxidant role under oxidative stress by inducing antioxidants. Some probiotics can produce butyrate; for example, based on evidence, MIYAIRI 588 strain of Clostridium butyricum with the production of butyrate has been able to improve rats with non-alcoholic fatty liver and exposed to oxidative stress [71].
4.4 Antioxidant signaling pathway mediated by probiotic bacteria
4.4.1 Nrf2-Keap1-ARE
Under oxidative stress, the expression of genes involved in the detoxification of ROS can be mediated through a pathway called Nrf2-Keap1-ARE (Figure 3) [72, 73]. In this pathway, the binding of Nrf2 to the antioxidant response element (ARE) sequences in the nucleus leads to the expression of factors related to the detoxification of ROS [74, 75, 76]. The activation or inhibition of Nrf2 depends on the amount of ROS. When the amount of ROS is low, the cytoplasmic inhibitor Keap1 binds to Nrf2, causing its proteasome degradation by polyubiquitination [77]; however, under oxidative stress, the functional structure of Keap1 changes due to the influence of the amino acid cysteine, which leads to the activation of Nrf2 and its entry into the nucleus and binding to the ARE sequences [74, 75, 76, 78].
Figure 3.
Nrf2-keap1-ARE pathway mediated by probiotics.
Probiotics can exert their antioxidant effects by regulating the Nrf2-Keap1-ARE pathway. According to research, probiotics such as Lactobacillus Plantarum FC225, Lactobacillus Plantarum CA16, and Lactobacillus Plantarum SC4 can increase the level of Nrf2 in the liver cells of hypertensive mice [79, 80]. The effect of Clostridium butyricium MIYAIRI 588 [71] and Bacillus amyloliquefaciens SC06 on increasing the level and regulation of Nrf2 expression in the studied animals has been shown [7].
4.4.2 NFκB
In inflammatory conditions, the expression of inflammatory cytokines is mediated by the transcription factor NFκB. This factor is activated by ROS. It can be said that NFκB is the first transcription factor that responds to oxidative stress [19]. Evidence suggests that probiotics may inhibit NFκB by their antioxidant power, and thus play a role in preventing inflammation. Inhibition of NFκB and stimulation of heat shock proteins (Hsps) in colon epithelial cells by probiotic mixture VSL # 3 and also the effect of Bacillus sp. strain LBP32 in the prevention of inflammation in RAW 264.7 macrophages are examples of the antioxidant effect of probiotics by inhibiting NFκB [81, 82].
4.4.3 MAPK
Among the four subfamilies of mitogen-activated protein kinases (MAPKs), c-jun N-terminal kinase (JNKs) and p38-MAPK are key enzymes involved in response to various stresses (UV irradiation and osmotic shock), and extracellular regulated protein kinases (ERKs) have an important role in anabolic metabolisms [83, 84]. These are the best-known mitogen-activated protein kinases [85].
Based on studies, some probiotics, such as Lactobacillus GG, can activate MAPK in the young adult mouse colon (YAMC) cells. Soluble agents in the conditioned media from the probiotic Lactobacillus GG (Lactobacillus GG-CM) in these cells stimulate Hsp25 and Hsp72. MAPK signaling pathways are involved in the expression and stimulation of Hsps in treated cells, so inhibition of p38 and JNK in the YAMC and then treatment with the probiotic Lactobacillus GG-CM stops the expression of Hsp72 [86]. In addition, the soluble proteins p40 and p75 produced by the probiotic Lactobacillus rhamnosus GG via the MAPK pathway can correct the dysfunction of epithelial cell barriers caused by a potent oxidant [85].
4.4.4 PKC
The control of the phosphorylation function of hydroxyl groups of serine and threonine residues in proteins is associated with Protein kinase C (PKC). PKC is also cellular messenger molecule that plays a role in various pathways, including regulation of cell growth and death and response to stresses. This molecule is very sensitive to redox modification, as well [87, 88, 89]. On the other hand, some probiotics can affect PKC activity. Corresponding to the previous report (Seth et al., 2008), inhibition of Ro-32-0432 (PKC inhibitor) by soluble proteins p40 and p75 produced by L. rhamnosus GG improves H2O2-induced epithelial barrier disorder [85].
4.5 Regulation of the ROS producing enzymes
Production of ROS through enzymatic reactions and various chemical processes in the host body is essential [90]; because they play an important role in defense and messaging functions [91]. The human NADPH oxidase (NOX) complex, as the main source of reactive oxygen species [92, 93, 94], has seven homologs (NOX1–5, dual oxidase 1 (DUOX1), and DUOX2) [91]. Membrane-bound NOX2 catalytic subunits and p22phox in combination with cytosolic agents (e.g., p40phox, p47phox, p67phox, and small GTPase RAC1, called by neutrophils) cause a respiratory burst (Figure 4) [95, 96]. However, oxidative stress occurs if there is an imbalance in the production of ROS or a decrease in the level of oxygen-scavenging proteins, which leads to tissue damage and cell death [93].
Figure 4.
NADPH oxidase (NOX) complex regulated by probiotics.
Probiotics are able to affect the production of ROS by the NOX complex. Based on researches, the probiotic Bacillus amyloliquefaciens SC06 reduces the activity of NOX and expression of p47phox (H2O2-induced IPEC-1) and the probiotics Lactobacillus fermentum CECT5716, Lactobacillus coryniformis CECT5711 (K8) and Lactobacillus gasseri CECT5714 (LC9) reduce NOX activity and decrease the mRNA expression of NOX-1 and NOX-4 enzymes (in hypertensive rats), as a result, they reduce the production level of ROS [7, 97].
On the other hand, ROS can be produced during prostaglandin biosynthesis. For example, cyclo-oxygenase (COX) participates in process of prostaglandin biosynthesis [98]. In some diseases, such as atherosclerosis, COX-2 expression is increased [99]. Therefore, it can be said that the production of vascular prostanoids is caused by overexpression of the COX-2 enzyme [100]. Studies have shown that some probiotics can reduce the expression of COX-2 in the host; for example, the commercial probiotic Lacidofil, when used in mice infected with Helicobacter pylori [101]. Furthermore, it has been established that the expression of COX-2 is reduced by Lactobacillus acidophilus in Catla thymus macrophages [102].
Improper functioning of cytochrome P450 (CYP) enzymes is associated with overproduction of ROS and oxidative stress conditions [103]; because they are involved in the metabolism of xenobiotic substances [104]. Some probiotics reduce the expression of these enzymes. Matuskova et al. reported Lactobacillus casei is involved in reducing the expression of CYP1A1 enzyme in the intestines of male rats [105].
4.6 Modulation of the intestinal microbiota
Studies have shown that some probiotics can be used to treat intestinal diseases [106, 107] because they have the ability to improve the oxidative stress created by changing the composition of the microbiota. In fact, probiotics show their antioxidant properties by settling in the gastrointestinal tract [108, 109] to regulate the altered microbiota composition and prevent the proliferation of harmful bacteria. Based on researches, Lactobacillus and Bifidobacterium are among the probiotics that prevent the growth of pathogenic bacteria by lowering the pH of the intestine; as a result, a balance is established in the composition of the microbiota [110, 111]. In addition, some probiotics produce toxic compounds (such as organic acids, bactericides, and biosurfactants) against pathogenic microorganisms [112]. For example, Lactobacillus rhamnosus GG, suppresses different bacteria by producing antimicrobial compounds [113]. As previously mentioned, the use of probiotics leads to improving oxidative stress by modulating the composition of gut microbiota and reducing the abundance of harmful bacteria.
Probiotics are microorganisms, when consumed in appropriate doses, can be beneficial to humans in a variety of biological manners. In the last few years, probiotics with antioxidant potential that have the ability to cope with oxidative stress have received much attention. Therefore, extensive studies have shown that the use of these probiotics can improve health in patients who experience different oxidative stress conditions. Known mechanisms that probiotics use to counteract with reactive oxygen species include chelating metal ions, affecting enzymes, metabolites, antioxidant signaling pathways, and modulating intestinal microbial composition. However, more research is required on the type of probiotics and their dosage. Ultimately, probiotics can regard as the therapeutic potential for inflammatory disease.
1.Schieber M, Chandel NS. ROS function in redox signaling and oxidative stress. Current Biology. 2014;24(10):R453-R462
2.Mishra V, Shah C, Mokashe N, Chavan R, Yadav H, Prajapati J. Probiotics as potential antioxidants: A systematic review. Journal of Agricultural and Food Chemistry. 2015;63(14):3615-3626
3.Luo D, Fang B. Structural identification of ginseng polysaccharides and testing of their antioxidant activities. Carbohydrate Polymers. 2008;72(3):376-381
4.Williams NT. Probiotics. American Journal of Health Pharmacy. 2010;67(6):449-458
5.Lin MY, Yen CL. Antioxidative ability of lactic acid bacteria. Journal of Agricultural and Food Chemistry. 1999;47(4):1460-1466
6.Shen Q , Shang N, Li P. In vitro and in vivo antioxidant activity of bifidobacterium animalis 01 isolated from centenarians. Current Microbiology. 2011;62(4):1097-1103
7.Wang Y, Wu Y, Wang Y, Fu A, Gong L, Li W, et al. Bacillus amyloliquefaciens SC06 alleviates the oxidative stress of IPEC-1 via modulating Nrf2/Keap1 signaling pathway and decreasing ROS production. Applied Microbiology and Biotechnology. 2017;101(7):3015-3026
8.Persichetti E, De Michele A, Codini M, Traina G. Antioxidative capacity of Lactobacillus fermentum LF31 evaluated invitro by oxygen radical absorbance capacity assay. Nutrition. 2014;30(7-8):936-938
9.Halliwell B, Cross CE. Oxygen-derived species: Their relation to human disease and environmental stress. Environmental Health Perspectives. 1994;102(Suppl. 10):5-12
10.Cross CE, Halliwell B, Borish ET, Pryor WA, Ames BN, Saul RL, et al. Oxygen radicals and human disease. Annals of International Medicine. 1987;107(4):526-545
11.Ames BN, Shigenaga MK, Hagen TM. Oxidants, antioxidants, and the degenerative diseases of aging. Proceedings of the National Academy of Sciences of the United States of America. 1993;90(17):7915-7922
12.Eftekharzadeh B, Maghsoudi N, Khodagholi F. Stabilization of transcription factor Nrf2 by tBHQ prevents oxidative stress-induced amyloid β formation in NT2N neurons. Biochimie. 2010;92(3):245-253
13.Harrison D, Griendling KK, Landmesser U, Hornig B, Drexler H. Role of oxidative stress in atherosclerosis. The American Journal of Cardiology. 2003;91(3):7-11
14.Ostrakhovitch EA, Afanas’ev IB. Oxidative stress in rheumatoid arthritis leukocytes: Suppression by rutin and other antioxidants and chelators. Biochemical Pharmacology. 2001;62(6):743-746
15.Griendling KK, FitzGerald GA. Oxidative stress and cardiovascular injury Part I: Basic mechanisms and in vivo monitoring of ROS. Circulation. 2003;108(16):1912-1916
16.Ceriello A, Motz E. Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited. Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24(5):816-823
17.Morrell CN. Reactive oxygen species: Finding the right balance. Circulation Research. 2008;103(6):571-572
18.Finkel T. Signal transduction by reactive oxygen species. The Journal of Cell Biology. 2011;194(1):7-15
19.Schreck R, Rieber P, Baeuerle PA. Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-kappa B transcription factor and HIV-1. The EMBO Journal. 1991;10(8):2247-2258
21.Wang J, Tang H, Zhang C, Zhao Y, Derrien M, Rocher E, et al. Modulation of gut microbiota during probiotic-mediated attenuation of metabolic syndrome in high fat diet-fed mice. ISME Journal. 2015;9(1):1-15
22.Homayouni-Rad A, Soroush AR, Khalili L, Norouzi-Panahi L, Kasaie Z, Ejtahed HS. Diabetes management by probiotics: current knowledge and future pespective. International Journal Vitamin Nutrition Research. 2017;1(1):1-3
23.Gomes AC, Bueno AA, De Souza RGMH, Mota JF. Gut microbiota, probiotics and diabetes. Nutrition Journal. 2014;13(1):1-13
24.Holzapfel WH, Schillinger U. Introduction to pre- and probiotics. Food Research International. 2002;35(2-3):109-116
25.Huang HY, Korivi M, Tsai CH, Yang JH, Tsai YC. Supplementation of lactobacillus plantarum K68 and fruit-vegetable ferment along with high fat-fructose diet attenuates metabolic syndrome in rats with insulin resistance. Evidence-based Complementary and Alternative Medicine. 2013;2013
26.Zocco MA, Dal Verme LZ, Cremonini F, Piscaglia AC, Nista EC, Candelli M, et al. Efficacy of Lactobacillus GG in maintaining remission of ulcerative colitis. Alimentary Pharmacology & Therapeutics. 2006;23(11):1567-1574
27.Saez-Lara MJ, Gomez-Llorente C, Plaza-Diaz J, Gil A. The role of probiotic lactic acid bacteria and bifidobacteria in the prevention and treatment of inflammatory bowel disease and other related diseases: A systematic review of randomized human clinical trials. BioMed Research International. 2015;22
28.Liu YW, Su YW, Ong WK, Cheng TH, Tsai YC. Oral administration of Lactobacillus plantarum K68 ameliorates DSS-induced ulcerative colitis in BALB/c mice via the anti-inflammatory and immunomodulatory activities. International Immunopharmacology. 2011;11(12):2159-2166
29.Dawood MAO, Koshio S, Ishikawa M, Yokoyama S, El Basuini MF, Hossain MS, et al. Effects of dietary supplementation of Lactobacillus rhamnosus or/and Lactococcus lactis on the growth, gut microbiota and immune responses of red sea bream, Pagrus major. Fish Shellfish Immunology. 2016;49:275-285
30.Dawood MAO, Koshio S, Ishikawa M, El-Sabagh M, Esteban MA, Zaineldin AI. Probiotics as an environment-friendly approach to enhance red sea bream, Pagrus major growth, immune response and oxidative status. Fish & Shellfish Immunology. 2016;57:170-178
31.Whorwell PJ, Altringer L, Morel J, Bond Y, Charbonneau D, O’Mahony L, et al. Efficacy of an encapsulated probiotic Bifidobacterium infantis 35624 in women with irritable bowel syndrome. The American Journal of Gastroenterology. 2006;101(7):1581-1590
32.Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K, Earley ZM, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science (80-). 2015;350(6264):1084-1089
33.Lei K, Li YL, Yu DY, Rajput IR, Li WF. Influence of dietary inclusion of Bacillus licheniformis on laying performance, egg quality, antioxidant enzyme activities, and intestinal barrier function of laying hens. Poultry Science. 2013;92(9):2389-2395
34.Stecchini ML, Del Torre M, Munari M. Determination of peroxy radical-scavenging of lactic acid bacteria. International Journal of Food Microbiology. 2001;64(1-2):183-188
35.Kullisaar T, Zilmer M, Mikelsaar M, Vihalemm T, Annuk H, Kairane C, et al. Two antioxidative lactobacilli strains as promising probiotics. International Journal of Food Microbiology. 2002;72(3):215-224
36.Asemi Z, Zare Z, Shakeri H, Sabihi SS, Esmaillzadeh A. Effect of multispecies probiotic supplements on metabolic profiles, hs-CRP, and oxidative stress in patients with Type 2 Diabetes. Annals of Nutrition & Metabolism. 2013;63(1-2):1-9
37.Martarelli D, Verdenelli MC, Scuri S, Cocchioni M, Silvi S, Cecchini C, et al. Effect of a probiotic intake on oxidant and antioxidant parameters in plasma of athletes during intense exercise training. Current Microbiology. 2011;62(6):1689-1696
38.Michelotti A, Cestone E, De Ponti I, Giardina S, Pisati M, Spartà E, et al. Efficacy of a probiotic supplement in patients with atopic dermatitis: A randomized, double-blind, placebo-controlled clinical trial. European Journal of Dermatology. 2021;31(2):225-232
39.Cannarella LAT, Mari NL, Alcântara CC, Iryioda TMV, Costa NT, Oliveira SR, et al. Mixture of probiotics reduces inflammatory biomarkers and improves the oxidative/nitrosative profile in people with rheumatoid arthritis. Nutrition. 2021;1:89
40.Macnaughtan J, Figorilli F, García-López E, Lu H, Jones H, Sawhney R, et al. A double-blind, Randomized Placebo-controlled trial of probiotic lactobacillus casei shirota in stable cirrhotic patients. Nutrients. 2020;12:6
41.Hajifaraji M, Jahanjou F, Abbasalizadeh F, Aghamohammadzadeh N, Abbasi MM, Dolatkhah N. Effect of probiotic supplements in women with gestational diabetes mellitus on inflammation and oxidative stress biomarkers: A randomized clinical trial. Asia Pacific Journal of Clinical Nutrition. 2018;27(3):581-591
42.Akkasheh G, Kashani-Poor Z, Tajabadi-Ebrahimi M, Jafari P, Akbari H, Taghizadeh M, et al. Clinical and metabolic response to probiotic administration in patients with major depressive disorder: A randomized, double-blind, placebo-controlled trial. Nutrition. 2016;32(3):315-320
43.Chong HX, Yusoff NAA, Hor YY, Lew LC, Jaafar MH, Choi SB, et al. Lactobacillus plantarum DR7 improved upper respiratory tract infections via enhancing immune and inflammatory parameters: A randomized, double-blind, placebo-controlled study. Journal of Dairy Science. 2019;102(6):4783-4797
44.Ito M, Kusuhara S, Yokoi W, Sato T, Ishiki H, Miida S, et al. Streptococcus thermophilus fermented milk reduces serum MDA-LDL and blood pressure in healthy and mildly hypercholesterolaemic adults. Beneficial Microbes. 2017;8(2):171-178
45.Gutteridge JMC, Richmond R, Halliwell B. Inhibition of the iron-catalysed formation of hydroxyl radicals from superoxide and of lipid peroxidation by desferrioxamine. The Biochemical Journal. 1979;184(2):469-472
46.Lee J, Hwang KT, Chung MY, Cho DH, Park CS. Resistance of Lactobacillus casei KCTC 3260 to Reactive Oxygen Species (ROS): Role for a Metal Ion Chelating Effect. Journal of Food Science. 2005;70(8):m388-m391
47.Ahire JJ, Mokashe NU, Patil HJ, Chaudhari BL. Antioxidative potential of folate producing probiotic Lactobacillus helveticus CD6. Journal of Food Science and Technology. 2011;50(1):26-34
48.Halliwell B, Murcia MA, Chirico S, Aruoma OI. Free radicals and antioxidants in food and in vivo: What they do and how they work. Critical Reviews in Food Science & Nutrition. 1 Jan 1995;35(1-2):7-20
49.Landis GN, Tower J. Superoxide dismutase evolution and life span regulation. Mechanisms of Ageing and Development. 2005;126(3):365-379
50.Davies K. Oxidative stress, antioxidant defenses, and damage removal, repair, and replacement systems. IUBMB Life. 2000;50(4-5):279-289
51.LeBlanc JG, del Carmen S, Miyoshi A, Azevedo V, Sesma F, Langella P, et al. Use of superoxide dismutase and catalase producing lactic acid bacteria in TNBS induced Crohn’s disease in mice. Journal of Biotechnology. 2011;151(3):287-293
52.Koc M, Taysi S, Buyukokuroglu ME, Bakan N. Melatonin protects rat liver against irradiation-induced oxidative injury. Journal of Radiation Research. 2003;44(3):211-215
53.Seguí J, Gironella M, Sans M, Granell S, Gil F, Gimeno M, et al. Superoxide dismutase ameliorates TNBS-induced colitis by reducing oxidative stress, adhesion molecule expression, and leukocyte recruitment into the inflamed intestine. Journal of Leukocyte Biology. 2004;76(3):537-544
54.Mollà M, Gironella M, Salas A, Closa D, Biete A, Gimeno M, et al. Protective effect of superoxide dismutase in radiation-induced intestinal inflammation. International Journal of Radiation Oncology, Biology, Physics. 2005;61(4):1159-1166
55.Ho YS, Xiong Y, Ma W, Spector A, Ho DS. Mice lacking catalase develop normally but show differential sensitivity to oxidant tissue injury *. The Journal of Biological Chemistry. 2004;279(31):32804-32812
56.De Moreno De LeBlanc A, LeBlanc JG, Perdigón G, Miyoshi A, Langella P, Azevedo V, et al. Oral administration of a catalase-producing Lactococcus lactis can prevent a chemically induced colon cancer in mice. Journal of Medical Microbiology. 2008;57(1):100-105
57.Wang AN, Yi XW, Yu HF, Dong B, Qiao SY. Free radical scavenging activity of Lactobacillus fermentum in vitro and its antioxidative effect on growing–finishing pigs. Journal of Applied Microbiology. 2009;107(4):1140-1148
58.Aluwong T, Kawu M, Raji M, Dzenda T, Govwang F, Sinkalu V, et al. Effect of yeast probiotic on growth, antioxidant enzyme activities and malondialdehyde concentration of broiler chickens. Antioxidants. 2013;2(4):326-339
59.Ejtahed HS, Mohtadi-Nia J,Homayouni-Rad A, Niafar M, Asghari-Jafarabadi M, Mofid V. Probiotic yogurt improves antioxidant status in type 2 diabetic patients. Nutrition. 2012;28(5):539-543
60.Pompei A, Cordisco L, Amaretti A, Zanoni S, Matteuzzi D, Rossi M. Folate production by bifidobacteria as a potential probiotic property. Applied and Environmental Microbiology. 2007;73(1):179-185
61.Pompei A, Cordisco L, Amaretti A, Zanoni S, Raimondi S, Matteuzzi D, et al. Administration of folate-producing bifidobacteria enhances folate status in Wistar rats. The Journal of Nutrition. 2007;137(12):2742-2746
62.Strozzi GP, Mogna L. Quantification of folic acid in human feces after administration of Bifidobacterium probiotic strains. Journal of Clinical Gastroenterology. 2008;42(Suppl. 3):2
63.Mohammad MA, Molloy A, Scott J, Hussein L. Plasma cobalamin and folate and their metabolic markers methylmalonic acid and total homocysteine among Egyptian children before and after nutritional supplementation with the probiotic bacteria Lactobacillus acidophilus in yoghurt matrix. International Journal of Food Sciences and Nutrition. 1 Jan 2006;57(7-8):470-480
64.Al-Maskari MY, Waly MI, Ali A, Al-Shuaibi YS, Ouhtit A. Folate and vitamin B12 deficiency and hyperhomocysteinemia promote oxidative stress in adult type 2 diabetes. Nutrition. 2012;28(7-8):e23-e26
65.Nandi D, Patra RC, Swarup D. Effect of cysteine, methionine, ascorbic acid and thiamine on arsenic-induced oxidative stress and biochemical alterations in rats. Toxicology. 2005;211(1-2):26-35
66.Mehta R, Dedina L, O’Brien PJ. Rescuing hepatocytes from iron-catalyzed oxidative stress using vitamins B1 and B6. Toxicology in Vitro. 2011;25(5):1114-1122
67.Fabian E, Majchrzak D, Dieminger B, Meyer E, Elmadfa I. Influence of probiotic and conventional yoghurt on the status of vitamins B1, B2 and B6 in young healthy women. Annals of Nutrition & Metabolism. 2008;52(1):29-36
68.Zilmer M, Soomets U, Rehema A, Langel Ü. The glutathione system as an attractive therapeutic target. Drug Design Review Online. 2005;2(2):121-127
69.Kullisaar T, Songisepp E, Aunapuu M, Kilk K, Arend A, Mikelsaar M, et al. Complete glutathione system in probiotic Lactobacillus fermentum ME-3. Applied Biochemical Microbiology. 2010;46(5):481-486
70.Kau AL, Ahern PP, Griffin NW, Goodman AL, Gordon JI. Human nutrition, the gut microbiome and the immune system. Nature. 2011;474(7351):327-336
71.Endo H, Niioka M, Kobayashi N, Tanaka M, Watanabe T. Butyrate-producing probiotics reduce nonalcoholic fatty liver disease progression in rats: New insight into the probiotics for the gut-liver axis. PLoS One. 2013;8(5):e63388
72.Kobayashi M, Li L, Iwamoto N, Nakajima-Takagi Y, Kaneko H, Nakayama Y, et al. The antioxidant defense system Keap1-Nrf2 comprises a multiple sensing mechanism for responding to a wide range of chemical compounds. Molecular and Cellular Biology. 2009;29(2):493-502
73.Jones RM, Desai C, Darby TM, Luo L, Wolfarth AA, Scharer CD, et al. Lactobacilli modulate epithelial cytoprotection through the Nrf2 pathway. Cell Reports. 2015;12(8):1217-1225
74.Zhang DD. Mechanistic studies of the Nrf2-Keap1 signaling pathway. Drug Metabolism Reviews. 1 Jan 2006;38(4):769-789
75.Klaassen CD, Reisman SA. Nrf2 the rescue: Effects of the antioxidative/electrophilic response on the liver. Toxicology and Applied Pharmacology. 2010;244(1):57-65
76.Maher J, Yamamoto M. The rise of antioxidant signaling—The evolution and hormetic actions of Nrf2. Toxicology and Applied Pharmacology. 2010;244(1):4-15
77.Zhang DD, Lo S-C, Cross JV, Templeton DJ, Hannink M. Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex. Molecular and Cellular Biology. 2004;24(24):10941-10953
78.Motohashi H, Yamamoto M. Nrf2–Keap1 defines a physiologically important stress response mechanism. Trends in Molecular Medicine. 2004;10(11):549-557
79.Wang LX, Liu K, Gao DW, Hao JK. Protective effects of two Lactobacillus plantarum strains in hyperlipidemic mice. World Journal of Gastroenterology. 2013;19(20):3150-3156
80.Gao D, Gao Z, Zhu G. Antioxidant effects of Lactobacillus plantarum via activation of transcription factor Nrf2. Food & Function. 2013;4(6):982-989
81.Diao Y, Xin Y, Zhou Y, Li N, Pan X, Qi S, et al. Extracellular polysaccharide from Bacillus sp. strain LBP32 prevents LPS-induced inflammation in RAW 264.7 macrophages by inhibiting NF-κB and MAPKs activation and ROS production. International Immunopharmacology. 2014;18(1):12-19
82.Petrof EO, Kojima K, Ropeleski MJ, Musch MW, Tao Y, De Simone C, et al. Probiotics inhibit nuclear factor-κB and induce heat shock proteins in colonic epithelial cells through proteasome inhibition. Gastroenterology. 2004;127(5):1474-1487
83.Widmann C, Gibson S, Jarpe MB, Johnson GL. Mitogen-activated protein kinase: Conservation of a three-kinase module from yeast to human. Physiological Reviews. 1999;79(1):143-180
84.Kyriakis JM, Avruch J. Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiological Reviews. 2001;81(2):807-869
85.Seth A, Yan F, Polk DB, Rao RK. Probiotics ameliorate the hydrogen peroxide-induced epithelial barrier disruption by a PKC-and MAP kinase-dependent mechanism. American Journal of Physiology-Gastrointestinal and Liver Physiology. Apr 2008;294(4):G1060-9
86.Tao Y, Drabik KA, Waypa TS, Musch MW, Alverdy JC, Schneewind O, et al. Soluble factors from Lactobacillus GG activate MAPKs and induce cytoprotective heat shock proteins in intestinal epithelial cells. American Journal of Physiology-Cell Physiology. Apr 2006;290(4):C1018-30
87.Blumberg PM. Complexities of the protein kinase C pathway. Molecular Carcinogenesis. 1991;4(5):339-344
88.Stabel S, Parker PJ. Protein kinase C. Pharmacology & Therapeutics. 1991;51(1):71-95
89.Gopalakrishna R, Chen ZH, Gundimeda U. Modifications of cysteine-rich regions in protein kinase C induced by oxidant tumor promoters and enzyme-specific inhibitors. Methods in Enzymology. 1995;252(C):132-146
90.Lin CC, Hsieh HL, Shih RH, Chi PL, Cheng SE, Chen JC, et al. NADPH oxidase 2-derived reactive oxygen species signal contributes to bradykinin-induced matrix metalloproteinase-9 expression and cell migration in brain astrocytes. Cell Communication and Signaling. Dec 2012;10(1):1-5
91.Aguirre J, Lambeth JD. Nox enzymes from fungus to fly to fish and what they tell us about Nox function in mammals. Free Radical Biology & Medicine. 2010;49(9):1342-1353
92.Rahman I, Biswas SK, Kode A. Oxidant and antioxidant balance in the airways and airway diseases. European Journal of Pharmacology. 2006;533(1-3):222-239
93.Lin CC, Yang CC, Wang CY, Tseng HC, Pan CS, Hsiao LD, et al. NADPH oxidase/ROS-dependent VCAM-1 induction on TNF-α-challenged human cardiac fibroblasts enhances monocyte adhesion. Frontier in Pharmacology. 28 Jan 2016;6:310
94.Lee IT, Yang CM. Inflammatory signalings involved in airway and pulmonary diseases. Mediators of Inflammation. 2013;2013
95.Holmström KM, Finkel T. Cellular mechanisms and physiological consequences of redox-dependent signalling. Nature Reviews. Molecular Cell Biology. 2014;15(6):411-421
96.Bedard K, Krause KH. The NOX family of ROS-generating NADPH oxidases: Physiology and pathophysiology. Physiological Reviews. 2007;87(1):245-313
97.Gómez-Guzmán M, Toral M, Romero M, Jiménez R, Galindo P, Sánchez M, et al. Antihypertensive effects of probiotics Lactobacillus strains in spontaneously hypertensive rats. Molecular Nutrition & Food Research. 2015;59(11):2326-2336
98.Hussain T, Gupta S, Mukhtar H. Cyclooxygenase-2 and prostate carcinogenesis. Cancer Letters. 2003;191(2):125-135
99.Schonbeck U, Sukhova GK, Graber P, Coulter S, Libby P. Augmented expression of cyclooxygenase-2 in human atherosclerotic lesions. The American Journal of Pathology. 1999;155(4):1281-1291
100.Belton O, Byrne D, Kearney D, Leahy A, Fitzgerald DJ. Cyclooxygenase-1 and -2-dependent prostacyclin formation in patients with atherosclerosis. Circulation. 2000;102(8):840-845
101.Brzozowski T, Konturek PC, Mierzwa M, Drozdowicz D, Bielanski W, Kwiecien S, et al. Effect of probiotics and triple eradication therapy on the cyclooxygenase (COX)-2 expression, apoptosis, and functional gastric mucosal impairment in Helicobacter pylori-infected Mongolian gerbils. Helicobacter. 2006;11(1):10-20
102.Patel B, Kumar P, Banerjee R, Basu M, Pal A, Samanta M, et al. Lactobacillus acidophilus attenuates Aeromonas hydrophila induced cytotoxicity in catla thymus macrophages by modulating oxidative stress and inflammation. Molecular Immunology. 2016;75:69-83
103.Zangar RC, Davydov DR, Verma S. Mechanisms that regulate production of reactive oxygen species by cytochrome P450. Toxicology and Applied Pharmacology. 2004;199(3):316-331
104.Bondy SC, Naderi S. Contribution of hepatic cytochrome P450 systems to the generation of reactive oxygen species. Biochemical Pharmacology. 1994;48(1):155-159
105.Matušková Z, Šiller M, Tunková A, Anzenbacherová E, Zachařová A, Hogenová HT, et al. Effects of Lactobacillus casei on the expression and the activity of cytochromes P450 and on the CYP mRNA level in the intestine and the liver of male rats. Neuroendocrinology Letters. 2011;32(1):22167211
106.O’Toole PW, Cooney JC. Probiotic bacteria influence the composition and function of the intestinal microbiota. Interdisciplinary Perspectives on Infectious Diseases. 2008;2008:1-9
107.Butel MJ. Probiotics, gut microbiota and health. Médecine et Maladies Infectieuses. 2014;44(1):1-8
108.Bhardwaj A, Kaur G, Gupta H, Vij S, Malik RK. Interspecies diversity, safety and probiotic potential of bacteriocinogenic Enterococcus faecium isolated from dairy food and human faeces. World Journal of Microbiology and Biotechnology. 2010;27(3):591-602
109.Bhardwaj A, Malik RK, Chauhan P. Functional and safety aspects of enterococci in dairy foods. Indian Journal of Microbiology. 2008;48(3):317-325
110.Doron S, Gorbach SL. Probiotics: Their role in the treatment and prevention of disease. Expert Review of Anti-Infective Therapy. 2006;4(2):261-275
111.Alvarez-Olmos MI, Oberhelman RA. Probiotic agents and infectious diseases: A modern perspective on a traditional therapy. Clinical Infectious Diseases. 2001;32(11):1567-1576
112.Vanderhoof JA, Young RJ. Current and potential uses of probiotics. Annals of Allergy, Asthma & Immunology. 2004;93(5):S33-S37
113.Silva M, Jacobus NV, Deneke C, Gorbach SL. Antimicrobial substance from a human Lactobacillus strain. Antimicrobial Agents and Chemotherapy. 1987;31(8):1231
Written By
Arezu Heydari, Farshid Parvini and Najaf Allahyari Fard
Submitted: 27 February 2022Reviewed: 07 March 2022Published: 11 April 2022
Open access peer-reviewed chapter
