The *Bifidobacterim bifidum* (BIB2) Probiotic Increased Immune System Factors in Men Sprint Athletes

*Ali Hossein Khani, Seyed Milad Mousavi Jazayeri, Elahe Ebrahimi and Ayoub Farhadi*

## **Abstract**

Foods supplemented with probiotics enhance athletes' immune system functions, improve body health and consequently decreases athlete's health maintenance costs. Probiotics improve immune system function against pathogens via affecting on innate immune system, humeral immunity and cytokines. The effects of consumption of Iranian probiotic *Bifidobactrium bifidum* (BIB2) on athletes' immune system functions were evaluated. The results showed studied immune system factors were significantly different between test and control groups, so that IgA, IgM, lymphocyte and monocytes percentage and CD4 measurements of test group were higher than control. The *Bifidobacterim bifidum* (BIB2) probiotic consumption can affect some immune system factors; therefore its ability to improved general health should be studied more.

**Keywords:** probiotics, CD4, IgA, IgM, monocyte, lymphocyte, sprint athletes, *Bifidobactrium bifidum* (BIB2)

### **1. Introduction**

There is a general belief among elite athletes and their coaches that overtraining causes resistance to infection. Epidemiological studies report that symptoms of respiratory tract infection increases in 1–2 weeks after strenuous endurance competitions. The highest percentages of patients were athletes who exceeded their training threshold level that is associated with the training load [1, 2]. The biological balance of body organs improves the health of the host, improving performance and increasing power of the immune system [3]. Probiotics are a group of living microorganisms that improve health by improving biological balance when added to foods or consumed as supplements. These organisms increase immune system function and enhance host defense against harmful microorganisms. The benefits of probiotics such as reducing toxins, increase immunity and resistance to infection, produce vitamins and nutrients, organic acids, reduce allergic reactions, respiratory infections, reduce the symptoms of irritable bowel syndrome, arthritis, rheumatoid and modulating immune responses have been shown in many studies [4, 5]. Overwhelming exercise undertaken by athletes or military personnel diminishes

immune system function and increase gastrointestinal complaints, as well as increasing the risk of disease and infections [6–8]. In many studies, reduced immunity after chronic fatigue has been seen in over trained athletes [9–11]. Nieman et al. (2000) showed that regular and continuous exercise enhances the strength of athletes' immune system; while undertaking heavy and alternate physical activities had the reverse impact. Also, some research shows that excessive exercise also damages the immune system is impaired [12, 13].

The humoral immunity in athletes is often studied by mucosal immunoglobulin measurements, especially the changes in the secretion of IgA and IgM from tissue was reported in sporting activities [13]. Due to reduction of immunoglobulins in sport activities (and increased risk of infection in the upper respiratory tract) investigating the IgA and IgM is important [14]. Because the antibodies secretion, the lymphocytes have a very important role in the immune system [15]. Monocytes are the largest cells in the bloodstream and involved in phagocytosis in the early stages of the immune response. Also, monocytes produce the cytokines that activate lymphocytes and consequently stimulate inflammation [16]. Immune system malfunctions might be caused by stress, sleep disorder, exercise, and negative energy balance. Hard exercises raise neutrophil count; however, they decrease lymphocyte count, natural killer cell activity (NK cell) via disturbance with oxidative burst, neutrophil function, immunoglobulin's level and antimicrobial proteins level in saliva.

The effects of probiotics bacteria in improving immune function and preventing disease have been shown in numerous studies [6, 17–19]. The *Lactobacillus* and *Bifidobacterium* produce bactericidal and bacteriostatic agents such as lactic acid that can prevent pathogenic bacteria growth. Therefore probiotics reduce tissue inflammation directly or with antagonistic effects on pathogens [20, 21]. It has been shown that probiotics stimulate interferon-A secretion and this leads to increasing host phagocytic capacity [22, 23]. Kotani et al. reported that consuming *Lactobacillus* rised salivary IgA secretion [24]. Therefore, in this study the effects of juice supplemented by *Bifidobacterium bifidum* probiotic (2 × 109 cfu/ml) on immune factors including IgA, IgM, lymphocytes, monocytes and CD4 cells count were in the men's sprint athletes was investigated. The results could play an important role for athletes to overcome many diseases and infections, especially respiratory infections.

Effects of fruit juices supplemented by *Bifidobacterium bifidum* **(**BIB2) probiotic (2\*109 cfu/ml) was assessed on immune system function of sprint athletes. Hence, 56 male athletes aged 21 ± 3 years and average weights of 78 ± 5 kg which divided into 2 groups: the first group received a glass (200 cc) juices containing probiotic daily for 12 weeks and control group received only simple juice (placebo) without probiotic. All volunteers had general health and did not smoke. Also they were asked not to use any probiotics products and antibiotics during the survey. The athletes had three times exercise per week. Before experiment, the probiotic characteristics and testing process were explained for all participants. All athletes voluntary participated in the experiment.

#### **1.1 Blood sample collection**

First, prior to the tests, the blood samples were collected from athletes after fasting, then once a month 24 h after 100 meters running, 8 ml of blood were collected from both studied groups in EDTA tubes. The bloods were centrifuged at 5000 rpm for 15 min and serums were collected. The blood cell counting was done using cell counter device (BC-2000 Mindray).

**87**

**Table 1.**

*\*Standard division.*

*The* Bifidobacterim bifidum *(BIB2) Probiotic Increased Immune System Factors in Men Sprint…*

The IgA and IgM were measured using ELISA methodology using human IgA and IgM ELISA Kit (ab137980 and ab137982) according to protocol suggested by manufacture (abcam Inc., USA) using ELISA reader (Biotech microplate reader

Flow cytometry is a technique for counting microscopic particles. The CD4 cells count was measured by flow cytometry technique using BD FACSCalibur system and anti-CD4 monoclonal antibody and results were reported based on the percent

The obtained data were analyzed using Graphpad Prism (version 6.01) software

The results of present study showed that consuming probiotic supplemented fruit juice increased serum IgA level and can be boosted immune system activities (**Table 1**). According to results shown in chart 1, CD4 cells count increased after consuming probiotics (**Figure 2**, **Table 1**) and it probably affects immune system

Probiotics or their products could have antimicrobial activities or they can prevent colonization of pathogens [4]. They probably have adjuvant effect so they may be stimulate phagocytosis done by leucocytes or may be increase IgA and defensins secretion. They could be attached to gut immune receptors, thus they inhibit competitively pathogenic virus's or bacteria's attachment. In addition, competition occurs for earning foods and nutrition so with suitable colonization of probiotics,

Indigenous bacteria are accepted to add to the immunological protection of the host by making a hindrance against colonization by pathogenic microbes. This hindrance can be upset by sickness and by utilization of antibiotics, in this way, permitting less demanding access of the host gut by pathogens. It is presently trusted

Before test 364.954 ± 25.98 356.234 ± 42.36 First month 398.065 ± 40.24 350.568 ± 36.78 Second month 431.365 ± 37.96 358.653 ± 42.63 P-value <0.05

**Test group Control group Means ± SD\* Means ± SD**

**Time IgA (cell/μl)**

*The CD4 means ± standard deviation in test and control group.*

of peripheral blood mononuclear cell (PBMC) in total suspension.

*DOI: http://dx.doi.org/10.5772/intechopen.84222*

**1.3 The CD4 cells count measurements**

**1.2 The IgA and IgM measurements**

ELX800).

**1.4 Statistical analysis**

with 0.05 significant levels.

**2. Results and discussion**

ability to defense against antigens.

we can conquer pathogenic bacteria.

*The* Bifidobacterim bifidum *(BIB2) Probiotic Increased Immune System Factors in Men Sprint… DOI: http://dx.doi.org/10.5772/intechopen.84222*

#### **1.2 The IgA and IgM measurements**

*Nutraceuticals - Past, Present and Future*

level in saliva.

tory infections.

voluntary participated in the experiment.

counter device (BC-2000 Mindray).

**1.1 Blood sample collection**

otic (2\*109

ages the immune system is impaired [12, 13].

immune system function and increase gastrointestinal complaints, as well as increasing the risk of disease and infections [6–8]. In many studies, reduced immunity after chronic fatigue has been seen in over trained athletes [9–11]. Nieman et al. (2000) showed that regular and continuous exercise enhances the strength of athletes' immune system; while undertaking heavy and alternate physical activities had the reverse impact. Also, some research shows that excessive exercise also dam-

The humoral immunity in athletes is often studied by mucosal immunoglobulin measurements, especially the changes in the secretion of IgA and IgM from tissue was reported in sporting activities [13]. Due to reduction of immunoglobulins in sport activities (and increased risk of infection in the upper respiratory tract) investigating the IgA and IgM is important [14]. Because the antibodies secretion, the lymphocytes have a very important role in the immune system [15]. Monocytes are the largest cells in the bloodstream and involved in phagocytosis in the early stages of the immune response. Also, monocytes produce the cytokines that activate lymphocytes and consequently stimulate inflammation [16]. Immune system malfunctions might be caused by stress, sleep disorder, exercise, and negative energy balance. Hard exercises raise neutrophil count; however, they decrease lymphocyte count, natural killer cell activity (NK cell) via disturbance with oxidative burst, neutrophil function, immunoglobulin's level and antimicrobial proteins

The effects of probiotics bacteria in improving immune function and preventing disease have been shown in numerous studies [6, 17–19]. The *Lactobacillus* and *Bifidobacterium* produce bactericidal and bacteriostatic agents such as lactic acid that can prevent pathogenic bacteria growth. Therefore probiotics reduce tissue inflammation directly or with antagonistic effects on pathogens [20, 21]. It has been shown that probiotics stimulate interferon-A secretion and this leads to increasing host phagocytic capacity [22, 23]. Kotani et al. reported that consuming *Lactobacillus* rised salivary IgA secretion [24]. Therefore, in this study the effects

immune factors including IgA, IgM, lymphocytes, monocytes and CD4 cells count were in the men's sprint athletes was investigated. The results could play an important role for athletes to overcome many diseases and infections, especially respira-

Effects of fruit juices supplemented by *Bifidobacterium bifidum* **(**BIB2) probi-

Hence, 56 male athletes aged 21 ± 3 years and average weights of 78 ± 5 kg which divided into 2 groups: the first group received a glass (200 cc) juices containing probiotic daily for 12 weeks and control group received only simple juice (placebo) without probiotic. All volunteers had general health and did not smoke. Also they were asked not to use any probiotics products and antibiotics during the survey. The athletes had three times exercise per week. Before experiment, the probiotic characteristics and testing process were explained for all participants. All athletes

cfu/ml) was assessed on immune system function of sprint athletes.

First, prior to the tests, the blood samples were collected from athletes after fasting, then once a month 24 h after 100 meters running, 8 ml of blood were collected from both studied groups in EDTA tubes. The bloods were centrifuged at 5000 rpm for 15 min and serums were collected. The blood cell counting was done using cell

cfu/ml) on

of juice supplemented by *Bifidobacterium bifidum* probiotic (2 × 109

**86**

The IgA and IgM were measured using ELISA methodology using human IgA and IgM ELISA Kit (ab137980 and ab137982) according to protocol suggested by manufacture (abcam Inc., USA) using ELISA reader (Biotech microplate reader ELX800).

#### **1.3 The CD4 cells count measurements**

Flow cytometry is a technique for counting microscopic particles. The CD4 cells count was measured by flow cytometry technique using BD FACSCalibur system and anti-CD4 monoclonal antibody and results were reported based on the percent of peripheral blood mononuclear cell (PBMC) in total suspension.

#### **1.4 Statistical analysis**

The obtained data were analyzed using Graphpad Prism (version 6.01) software with 0.05 significant levels.

### **2. Results and discussion**

The results of present study showed that consuming probiotic supplemented fruit juice increased serum IgA level and can be boosted immune system activities (**Table 1**). According to results shown in chart 1, CD4 cells count increased after consuming probiotics (**Figure 2**, **Table 1**) and it probably affects immune system ability to defense against antigens.

Probiotics or their products could have antimicrobial activities or they can prevent colonization of pathogens [4]. They probably have adjuvant effect so they may be stimulate phagocytosis done by leucocytes or may be increase IgA and defensins secretion. They could be attached to gut immune receptors, thus they inhibit competitively pathogenic virus's or bacteria's attachment. In addition, competition occurs for earning foods and nutrition so with suitable colonization of probiotics, we can conquer pathogenic bacteria.

Indigenous bacteria are accepted to add to the immunological protection of the host by making a hindrance against colonization by pathogenic microbes. This hindrance can be upset by sickness and by utilization of antibiotics, in this way, permitting less demanding access of the host gut by pathogens. It is presently trusted


#### **Table 1.**

*The CD4 means ± standard deviation in test and control group.*

#### **Figure 1.**

*Potential roles of probiotic bacteria in the human intestinal tract. Probiotic bacteria may act in a variety of ways to prevent the growth and colonization of pathogenic bacteria.*

**Figure 2.**

*The CD4 cells count (cell/μl) differences between test and control group in sprint athletes.*

that this hindrance can be kept up by giving enhancements containing live 'alluring' microbes: such supplements are called probiotics [24].

n expansion to making a barrier impact, a few of the metabolic products of probiotic bacteria (e.g. lactic acid and a class of anti-microbial proteins named bacteriocins, created by a few bacteria) may hinder growth of pathogenic organisms. Moreover, the alluring bacteria may compete for nutrients with the pathogens. At last, there's a few prove that probiotic microbes may improve the intestine immune reaction against pathogenic microscopic organisms (**Figure 1**).

Studies in rats and mice uncover that lactic acid bacteria managed orally increment the numbers of T lymphocytes, CD4þ cells and antibody-secreting cells, counting those within the intestinal mucosa, and improve lymphocyte expansion, normal killer cell activity, IL-1, TNF and IFN-g generation, antibody production (counting secretory IgA), phagocytic activity and the respiratory burst of macrophages and the DTH reaction [21].

Hard and continues physical activities CAN decrease immune system function and it can lead to infectious diseases [25]. Probiotics have an important role to improve and boost an individual's health via pathogen growth prevention, amino

**89**

**Table 2.**

*\*Standard division.*

transmission [35].

*The* Bifidobacterim bifidum *(BIB2) Probiotic Increased Immune System Factors in Men Sprint…*

acids and vitamins production, detoxification, cholesterol reduction and allergic reaction inhibition [26]. In the present study, the effects of *Bifidobactrium bifidum* (BIB2) probioticwe on immune system factors of IgA and CD4 were evaluated. Results revealed significant differences between the control and test group, so that swimmers received probiotic juice had higher IgA level and CD4 cells (P < 0.05) count than control group (**Tables 1** and **2**, **Figures 2** and **3**). These increment might accelerate microphage activities and phagocytosis, in turn, boost immune system against respiratory infections and diseases [27]. Lee et al. reported that intake of *Lactobacillus casei* and *Bifidobacterium* improved immune system functions and

West et al. reported that probiotic consumption lead to mucosal immune system

improvement and also increased CD4 and dendritic cells [29]. In other research conducted by Ohashi et al. in the same field showed that increasing IgA level and cytokine secretion occurred during probiotic consumption [30]. Furthermore, it has been showed that probiotic consumption caused potent increasing in lymphocyte and NK cells count in peripheral blood samples and they improved immune system and general health while NK cells count reduction was determined during hard exercises [31, 32]. These results mentioned above were completely in accordance with our findings. Other studies have been done in the field of relationship between CD4 cells and probiotic consumption [33–35]. For example, Jensen et al. reported that consumption of *Bifidobactrium bifidum* probiotic increased CD4 cell, improved immune system functions and had anti-inflammatory effects [34]. Besides, findings obtained by Selbovitz et al. about the effects of probiotic on individuals suffered from acquired immune deficiency syndrome (AIDS) showed that probiotics could boost immune defense against viruses and could prevent virus

*Lactobacillus* and *Bifidobacterium* are normal inhabitants of the human adult gastrointestinal tract. Complex interactions occur between probiotic bacteria and the different constituents of the intestinal ecosystem (resident microflora and epithelial and immune cells). Mucosal epithelial surfaces, such as the gastrointestinal tract or respiratory tract that host a wide variety of different microorganisms from the external environment, are suitable sites for the onset of infection with pathogens. These levels are not protected. Different mechanisms of defense are involved in permanent and effective monitoring. Secretive secretion system plays an important role in this regard. IgA secretion (sIgA) is the dominant enzyme of the antibody in the secretion of the mammalian intestine. Most IgA is produced from suprapathic plasma cells that produce IgA polymer with the J chain (pIgA).

**Time IgA (μg/dl) IgM (μg/dl)**

*The IgA and IgM means ± standard deviation in test and control group.*

Before test 230 ± 47 210 ± 56 143 ± 28 129 ± 73 First month 237 ± 48 185 ± 78 147 ± 75 132 ± 84 Second month 248 ± 75 193 ± 65 150 ± 62 135 ± 46 Third month 253 ± 83 194 ± 42 152 ± 43 133 ± 73 P-value <0.05

**Test group Control group Test group Control group Means ± SD\* Means ± SD Means ± SD Means ± SD**

*DOI: http://dx.doi.org/10.5772/intechopen.84222*

decreased respiratory infections among athletes [28].

#### *The* Bifidobacterim bifidum *(BIB2) Probiotic Increased Immune System Factors in Men Sprint… DOI: http://dx.doi.org/10.5772/intechopen.84222*

acids and vitamins production, detoxification, cholesterol reduction and allergic reaction inhibition [26]. In the present study, the effects of *Bifidobactrium bifidum* (BIB2) probioticwe on immune system factors of IgA and CD4 were evaluated. Results revealed significant differences between the control and test group, so that swimmers received probiotic juice had higher IgA level and CD4 cells (P < 0.05) count than control group (**Tables 1** and **2**, **Figures 2** and **3**). These increment might accelerate microphage activities and phagocytosis, in turn, boost immune system against respiratory infections and diseases [27]. Lee et al. reported that intake of *Lactobacillus casei* and *Bifidobacterium* improved immune system functions and decreased respiratory infections among athletes [28].

West et al. reported that probiotic consumption lead to mucosal immune system improvement and also increased CD4 and dendritic cells [29]. In other research conducted by Ohashi et al. in the same field showed that increasing IgA level and cytokine secretion occurred during probiotic consumption [30]. Furthermore, it has been showed that probiotic consumption caused potent increasing in lymphocyte and NK cells count in peripheral blood samples and they improved immune system and general health while NK cells count reduction was determined during hard exercises [31, 32]. These results mentioned above were completely in accordance with our findings. Other studies have been done in the field of relationship between CD4 cells and probiotic consumption [33–35]. For example, Jensen et al. reported that consumption of *Bifidobactrium bifidum* probiotic increased CD4 cell, improved immune system functions and had anti-inflammatory effects [34]. Besides, findings obtained by Selbovitz et al. about the effects of probiotic on individuals suffered from acquired immune deficiency syndrome (AIDS) showed that probiotics could boost immune defense against viruses and could prevent virus transmission [35].

*Lactobacillus* and *Bifidobacterium* are normal inhabitants of the human adult gastrointestinal tract. Complex interactions occur between probiotic bacteria and the different constituents of the intestinal ecosystem (resident microflora and epithelial and immune cells). Mucosal epithelial surfaces, such as the gastrointestinal tract or respiratory tract that host a wide variety of different microorganisms from the external environment, are suitable sites for the onset of infection with pathogens. These levels are not protected. Different mechanisms of defense are involved in permanent and effective monitoring. Secretive secretion system plays an important role in this regard. IgA secretion (sIgA) is the dominant enzyme of the antibody in the secretion of the mammalian intestine. Most IgA is produced from suprapathic plasma cells that produce IgA polymer with the J chain (pIgA).


#### **Table 2.**

*The IgA and IgM means ± standard deviation in test and control group.*

*Nutraceuticals - Past, Present and Future*

that this hindrance can be kept up by giving enhancements containing live 'alluring'

Studies in rats and mice uncover that lactic acid bacteria managed orally increment the numbers of T lymphocytes, CD4þ cells and antibody-secreting cells, counting those within the intestinal mucosa, and improve lymphocyte expansion, normal killer cell activity, IL-1, TNF and IFN-g generation, antibody production (counting secretory IgA), phagocytic activity and the respiratory burst of macro-

Hard and continues physical activities CAN decrease immune system function and it can lead to infectious diseases [25]. Probiotics have an important role to improve and boost an individual's health via pathogen growth prevention, amino

n expansion to making a barrier impact, a few of the metabolic products of probiotic bacteria (e.g. lactic acid and a class of anti-microbial proteins named bacteriocins, created by a few bacteria) may hinder growth of pathogenic organisms. Moreover, the alluring bacteria may compete for nutrients with the pathogens. At last, there's a few prove that probiotic microbes may improve the intestine immune

*Potential roles of probiotic bacteria in the human intestinal tract. Probiotic bacteria may act in a variety of* 

microbes: such supplements are called probiotics [24].

*ways to prevent the growth and colonization of pathogenic bacteria.*

phages and the DTH reaction [21].

reaction against pathogenic microscopic organisms (**Figure 1**).

*The CD4 cells count (cell/μl) differences between test and control group in sprint athletes.*

**88**

**Figure 2.**

**Figure 1.**

#### **Figure 3.**

*The IgA concentration (mg/dl) differences between test and control group in sprint athletes.*

Epithelial cells express the specific Ig receptor (pIgR). They are very important for the selective transfer of immunoglobulins to the lumen of the intestine. Immunoglobulin classes IgG and IgM are also present in the intestinal secretions, but vary in amounts and isotypes based on animal species. SIgA has many benefits. The dimer and tetrameric forms of IgA contain 4 to 8 antigen binding sites and have several "rewards" agents similar to IgM. IgA is more resistant to the activity of proteolytic enzymes that occur in gastrointestinal secretions [18]. IgA-antigen complexes do not activate the complement with inflammatory outcomes. Thanks to the content of mannan oligosaccharide side chains, sIgA could inhibit the adherence of bacteria with type I fimbriae to epithelial cells regardless of any specific antibody response. The typical response of the secretory immune system is the production of specific secretory IgA antibodies against luminal antigens to prevent other later responses on the epithelial surface. This process is called the immune exclusion and provides non-inflammatory protection in the mucous membrane. The integrity of the epithelial layer, the production of mucus, glycolipid, cytoprotein peptides and antibiotic-like agents are other host protection systems [29]. Protective microflora makes boundary impacts against risky pathogens and makes administrative specialists, such as brief and biofine fatty acids of bacteria. This impact moreover incorporates competition for receptors and metabolic foundations. It is more stamped but less caught on by the part of intestinal microflora within the modulation of homeostasis. The mucosal layer of the digestive tract is known as one of the biggest immune organs known to all sorts of immune cells [12]. It is conceivable to characterize anatomically the acceptance and effector parts of the immune reaction interior of the mucosal immune system. The most acceptance places are Peyer's patches restricted along the total little digestive tract. Lymphoid and accessory cells of Peyer's patches are secured by the follicular epithelium with M cells that serve as antigen preparing cells within the intestinal divider. Lymphocyte migration is important for the transport of immunological information between the different compartments of the intestinal immune system. The dendritic cells are the primary antigen particular cells depleting from the guts after mesenteric lymph node resection, afterward specially T-cells recycled through the intestine wall. After movement into the intestinal lamina propria, the lymphocytes may enter the space between the epithelial cells where they are present as intra-epithelial lymphocytes.

**91**

with IEC or other T-cells [36].

*The* Bifidobacterim bifidum *(BIB2) Probiotic Increased Immune System Factors in Men Sprint…*

These intra-epithelial lymphocytes (IEL) may collectively constitute up to 27% of the epithelial cell populace and 40% of the peripheral T-cell populace. A tall extent of these cells is CD8+ (77% in pigs, 24% in sheep). They vary from blood T-cells. For case, they are CD90–, CD5– and carry an isoform of CD45 not found on peripheral blood T-cells. The division of the intestine wall from 5-day-old pigs come about in a 10-fold lower add up to lymphocyte surrender compared with grown-up pigs

intra-epithelial lymphocytes and 35.2 × 106

per g of tissue were gathered. Intestinal epithelial cells (IEC). They also contribute to the "education" of thymus independent subpopulations of intra-epithelial lymphocytes. Bacterial dependent activation of intestinal epithelial cells requires a direct contact with IEC and likely the interaction of surface molecules. For the start of the nearby resistant reaction and the actuation of particular T-cells, the entry of luminal antigens over the epithelial boundary is vital. Peyer's patches, or other lymphoid totals secured with a specialized epithelium layer with M cells are the most put for antigen section and T-cell actuation. The other sorts of immune cells such as macrophages, dendritic cells and enterocytes are moreover included within the handling of antigen at the mucosal level. T-lymphocytes from the intestinal lamina propria are ceaselessly beneath the antigen impact in vivo. They are actuated (IL-2 receptor expression, CD95) and viably respond to infection. Permanent antigen stimulation is responsible for the proliferation, maturation, and migration of T-cells to distant tissues where they act as effector cells in the immune response. T-cells produce lymphokines responsible for the aggregation of other types of immune cells (B cells, inflammatory cells) and for the modification of their microenvironment. One of the most important lymphokines is interferon γ (IFN-γ) produced by activated T-cells. It activates effector cells such as macrophages or epithelial cells (IEC) [29]. Murine IEC express MHC class II and ICAM-1 molecules and they display the antigen to T lymphocytes. This work is altered by the physiological or pathological status of the host. IEC are able to create in vitro a wide range of pro-inflammatory cytokines such as IL-8, MCP-1, TNF-α and GM-CSF in case they are affected by intrusive pathogenic bacteria. IL-8 and MCP are chemokines that pull in and actuate neutrophils and monocytes. TNF-α activate immune and inflammatory cells and GM-CSF incorporates a synergistic impact on cell actuation. The infiltration of the tissue with inflammatory effector cells to annihilate pathogens is continuously associated with a certain level of tissue harm. Subsequently the actuation is strictly controlled by external signals such as IFN-γ or TNF-α and by surface molecules like CD54 or CD95, which are able to enact or to discourage the actuation of IEC. There's a clear contrast between Gram-negative non-pathogenic microbes and lactic-acid bacteria (LAB) in their interaction with IEC. In coordinate interaction with IEC both types of bacteria actuate IFN-γ, but the stimulating impact of LAB is confined to the cellular surface molecule expression. The molecular mechanism responsible for these impacts of Gram-negative bacteria and LAB is not caught on. The capacity of Gram-negative bacteria to improve the expression of IFN-γ receptors on IEC increments the affectability of these cells to enactment with IFN-γ. On the other hand, LAB can stimulate IEC for successive actuation with this lymphokine, which is critical in local immune homeostasis. Permanent antigen stimulation of mucosal surfaces could create inflammatory lesions of the tissue. The homeostatic mechanisms should be active in the mucous layer to prohibit such undesirable effects. Apoptosis as programmed cell death shows one of the homeostatic mechanisms. Most of the T-lymphocytes in lamina propria are cells carrying a surface molecule – Fas that shifts apoptotic signals when it reacts with Fas ligand expressed on activated T-cells. Some T-cells also express Fas and Fas ligands that are potentially reactive

add up to lymphocytes

*DOI: http://dx.doi.org/10.5772/intechopen.84222*

where 26.8 × 106

#### *The* Bifidobacterim bifidum *(BIB2) Probiotic Increased Immune System Factors in Men Sprint… DOI: http://dx.doi.org/10.5772/intechopen.84222*

These intra-epithelial lymphocytes (IEL) may collectively constitute up to 27% of the epithelial cell populace and 40% of the peripheral T-cell populace. A tall extent of these cells is CD8+ (77% in pigs, 24% in sheep). They vary from blood T-cells. For case, they are CD90–, CD5– and carry an isoform of CD45 not found on peripheral blood T-cells. The division of the intestine wall from 5-day-old pigs come about in a 10-fold lower add up to lymphocyte surrender compared with grown-up pigs where 26.8 × 106 intra-epithelial lymphocytes and 35.2 × 106 add up to lymphocytes per g of tissue were gathered. Intestinal epithelial cells (IEC). They also contribute to the "education" of thymus independent subpopulations of intra-epithelial lymphocytes. Bacterial dependent activation of intestinal epithelial cells requires a direct contact with IEC and likely the interaction of surface molecules. For the start of the nearby resistant reaction and the actuation of particular T-cells, the entry of luminal antigens over the epithelial boundary is vital. Peyer's patches, or other lymphoid totals secured with a specialized epithelium layer with M cells are the most put for antigen section and T-cell actuation. The other sorts of immune cells such as macrophages, dendritic cells and enterocytes are moreover included within the handling of antigen at the mucosal level. T-lymphocytes from the intestinal lamina propria are ceaselessly beneath the antigen impact in vivo. They are actuated (IL-2 receptor expression, CD95) and viably respond to infection. Permanent antigen stimulation is responsible for the proliferation, maturation, and migration of T-cells to distant tissues where they act as effector cells in the immune response. T-cells produce lymphokines responsible for the aggregation of other types of immune cells (B cells, inflammatory cells) and for the modification of their microenvironment. One of the most important lymphokines is interferon γ (IFN-γ) produced by activated T-cells. It activates effector cells such as macrophages or epithelial cells (IEC) [29]. Murine IEC express MHC class II and ICAM-1 molecules and they display the antigen to T lymphocytes. This work is altered by the physiological or pathological status of the host. IEC are able to create in vitro a wide range of pro-inflammatory cytokines such as IL-8, MCP-1, TNF-α and GM-CSF in case they are affected by intrusive pathogenic bacteria. IL-8 and MCP are chemokines that pull in and actuate neutrophils and monocytes. TNF-α activate immune and inflammatory cells and GM-CSF incorporates a synergistic impact on cell actuation. The infiltration of the tissue with inflammatory effector cells to annihilate pathogens is continuously associated with a certain level of tissue harm. Subsequently the actuation is strictly controlled by external signals such as IFN-γ or TNF-α and by surface molecules like CD54 or CD95, which are able to enact or to discourage the actuation of IEC. There's a clear contrast between Gram-negative non-pathogenic microbes and lactic-acid bacteria (LAB) in their interaction with IEC. In coordinate interaction with IEC both types of bacteria actuate IFN-γ, but the stimulating impact of LAB is confined to the cellular surface molecule expression. The molecular mechanism responsible for these impacts of Gram-negative bacteria and LAB is not caught on. The capacity of Gram-negative bacteria to improve the expression of IFN-γ receptors on IEC increments the affectability of these cells to enactment with IFN-γ. On the other hand, LAB can stimulate IEC for successive actuation with this lymphokine, which is critical in local immune homeostasis. Permanent antigen stimulation of mucosal surfaces could create inflammatory lesions of the tissue. The homeostatic mechanisms should be active in the mucous layer to prohibit such undesirable effects. Apoptosis as programmed cell death shows one of the homeostatic mechanisms. Most of the T-lymphocytes in lamina propria are cells carrying a surface molecule – Fas that shifts apoptotic signals when it reacts with Fas ligand expressed on activated T-cells. Some T-cells also express Fas and Fas ligands that are potentially reactive with IEC or other T-cells [36].

*Nutraceuticals - Past, Present and Future*

Epithelial cells express the specific Ig receptor (pIgR). They are very important for the selective transfer of immunoglobulins to the lumen of the intestine. Immunoglobulin classes IgG and IgM are also present in the intestinal secretions, but vary in amounts and isotypes based on animal species. SIgA has many benefits. The dimer and tetrameric forms of IgA contain 4 to 8 antigen binding sites and have several "rewards" agents similar to IgM. IgA is more resistant to the activity of proteolytic enzymes that occur in gastrointestinal secretions [18]. IgA-antigen complexes do not activate the complement with inflammatory outcomes. Thanks to the content of mannan oligosaccharide side chains, sIgA could inhibit the adherence of bacteria with type I fimbriae to epithelial cells regardless of any specific antibody response. The typical response of the secretory immune system is the production of specific secretory IgA antibodies against luminal antigens to prevent other later responses on the epithelial surface. This process is called the immune exclusion and provides non-inflammatory protection in the mucous membrane. The integrity of the epithelial layer, the production of mucus, glycolipid, cytoprotein peptides and antibiotic-like agents are other host protection systems [29]. Protective microflora makes boundary impacts against risky pathogens and makes administrative specialists, such as brief and biofine fatty acids of bacteria. This impact moreover incorporates competition for receptors and metabolic foundations. It is more stamped but less caught on by the part of intestinal microflora within the modulation of homeostasis. The mucosal layer of the digestive tract is known as one of the biggest immune organs known to all sorts of immune cells [12]. It is conceivable to characterize anatomically the acceptance and effector parts of the immune reaction interior of the mucosal immune system. The most acceptance places are Peyer's patches restricted along the total little digestive tract. Lymphoid and accessory cells of Peyer's patches are secured by the follicular epithelium with M cells that serve as antigen preparing cells within the intestinal divider. Lymphocyte migration is important for the transport of immunological information between the different compartments of the intestinal immune system. The dendritic cells are the primary antigen particular cells depleting from the guts after mesenteric lymph node resection, afterward specially T-cells recycled through the intestine wall. After movement into the intestinal lamina propria, the lymphocytes may enter the space between the epithelial cells where they are present as intra-epithelial lymphocytes.

*The IgA concentration (mg/dl) differences between test and control group in sprint athletes.*

**90**

**Figure 3.**

Consumption of *Bifidobactrium bifidum* probiotic improves immune system defense ability against viruses such as influenza and enteroviruses [37, 38]. Also, these results were confirmed by Hu et al. [39]. Our findings indicated that consumption of *Bifidobactrium bifidum* **(**BIB2) probiotic increases CD4 cells count and they possibly improve the immune system response. According to results of present study and researches have been mentioned before, daily consumption of probiotics products could improve general health of individuals without any side effects. The results of this study show that probiotic juice containing *Bifidobactrium bifidum* probiotic supplementation affecting athletes sprint immune factors and showed significant differences with the control group. According to the survey was taken before the tests the participants feel a better perception of juice Probiotics than the Probiotics capsules.

In the present study athletes who consume probiotic showed the monocyte and lymphocyte cells significantly higher than control group (**Figures 4** and **5**, **Table 3**). Kekkonen et al. showed that in runners who take probiotics lower respiratory infections and gastrointestinal symptoms were reported, but the study did not find any effect of changes in monocyte cells that are inconsistent with our results [6].

West et al. reported the protective effect of probiotics on respiratory infections. In professional athletes who practice a lot in the long and intensive period, body temperature increased, the secretion of IgA confusion is created and therefore interferes in mucosal immunity [29]. Cox investigated the effect of probiotic *Lactobacillus fermentum* for 4 months on the Champ elite endurance. Unlike the results of this study did not observe any change in serum IgA, which can be because of the species and strains of bacteria [7]. Ashraf et al. showed that probiotics strengthen the immune system without causing an inflammatory response and immune modulators and directly affects the mucosal immune system. They suggested that probiotics as a natural and healthy food can increase stress resistance and immunity [40]. Probiotics can increase IgA antibody secretion, increase in phagocytic activity of macrophages and enhance the specific immune effects [41]. In study by Sakai et al. the effect of *Lactobacillus gasseri* on stimulating the production of IgA was shown [42].

Zhao and colleagues showed that *Lactobacillus plantarum* and *Bacillus subtilis* increase activity of lysozyme, superoxide (SOD) and the concentration of IgM

**93**

**Figure 6.**

**Figure 5.**

*\*Standard division.*

**Table 3.**

*The* Bifidobacterim bifidum *(BIB2) Probiotic Increased Immune System Factors in Men Sprint…*

*DOI: http://dx.doi.org/10.5772/intechopen.84222*

*The lymphocyte percentage differences between test and control group in sprint.*

*The monocyte and lymphocytes means ± standard deviation in test and control group.*

*The IgM concentration (mg/dl) count differences between test and control group in sprint athletes.*

**Time Monocyte (%) Lymphocyte (%)**

Before test 3.85± 0.36 3.78 ± 0.42 32.7 ± 5.6 34.3 ± 4.8 First month 4.30± 0.65 3.77 ± 0.25 34.7 ± 6.4 33.6 ± 7.2 Second month 5.10± 0.42 3.78 ± 0.24 35.5 ± 5.7 33.1 ± 6.4 Third month 5.60± 1.2 3.91 ± 0.90 36.2 ± 7.3 33.7 ± 6.8 P-value <0.05

**Test group Control group Test group Control group Means ± SD\* Means ± SD Means ± SD Means ± SD**

**Figure 4.** *The monocytes percentage differences between test and control group in sprint athletes.*

*The* Bifidobacterim bifidum *(BIB2) Probiotic Increased Immune System Factors in Men Sprint… DOI: http://dx.doi.org/10.5772/intechopen.84222*

#### **Figure 5.**

*Nutraceuticals - Past, Present and Future*

Consumption of *Bifidobactrium bifidum* probiotic improves immune system defense ability against viruses such as influenza and enteroviruses [37, 38]. Also, these results were confirmed by Hu et al. [39]. Our findings indicated that consumption of *Bifidobactrium bifidum* **(**BIB2) probiotic increases CD4 cells count and they possibly improve the immune system response. According to results of present study and researches have been mentioned before, daily consumption of probiotics products could improve general health of individuals without any side effects. The results of this study show that probiotic juice containing *Bifidobactrium bifidum* probiotic supplementation affecting athletes sprint immune factors and showed significant differences with the control group. According to the survey was taken before the tests the participants feel a better perception of juice Probiotics than the Probiotics capsules. In the present study athletes who consume probiotic showed the monocyte and lymphocyte cells significantly higher than control group (**Figures 4** and **5**, **Table 3**). Kekkonen et al. showed that in runners who take probiotics lower respiratory infections and gastrointestinal symptoms were reported, but the study did not find any effect of changes in monocyte cells that are inconsistent with our results [6].

West et al. reported the protective effect of probiotics on respiratory infections. In professional athletes who practice a lot in the long and intensive period, body temperature increased, the secretion of IgA confusion is created and therefore interferes in mucosal immunity [29]. Cox investigated the effect of probiotic *Lactobacillus fermentum* for 4 months on the Champ elite endurance. Unlike the results of this study did not observe any change in serum IgA, which can be because of the species and strains of bacteria [7]. Ashraf et al. showed that probiotics strengthen the immune system without causing an inflammatory response and immune modulators and directly affects the mucosal immune system. They suggested that probiotics as a natural and healthy food can increase stress resistance and immunity [40]. Probiotics can increase IgA antibody secretion, increase in phagocytic activity of macrophages and enhance the specific immune effects [41]. In study by Sakai et al. the effect of

*Lactobacillus gasseri* on stimulating the production of IgA was shown [42].

*The monocytes percentage differences between test and control group in sprint athletes.*

Zhao and colleagues showed that *Lactobacillus plantarum* and *Bacillus subtilis* increase activity of lysozyme, superoxide (SOD) and the concentration of IgM

**92**

**Figure 4.**

*The lymphocyte percentage differences between test and control group in sprint.*


#### **Table 3.**

*The monocyte and lymphocytes means ± standard deviation in test and control group.*

#### **Figure 6.**

*The IgM concentration (mg/dl) count differences between test and control group in sprint athletes.*


#### **Table 4.**

*Comparsion the means of monocyte percentage between test and control group (n = 3) in sprint athletes.*


#### **Table 5.**

*Comparsion the means of lymphocyte percentage between test and control group (n = 3) in sprint athletes.*

that was consistent with our results [43]. In the present study in the athletes who drank juice containing the probiotic, the IgM was significantly higher than control group (**Figure 6** and **Table 2**). Probiotic bacteria in reaction with macrophage cells in tight junctions of epithelial cells, immune cells and dendritic cells led to the development of immune function, then macrophages and dendritic cells also generate immune responses through it. The dendritic cells spread their teeth between intestinal epithelial cells in the intestinal wall and use the probiotics to regulate immune function. The reaction of probiotic with intestinal epithelial cells induces the secretion of antimicrobial factors and cytokines and leading to activation of B and T lymphocytes in the lymphoid tissue of the gastrointestinal tract [6, 44, 32] (**Tables 4** and **5**).

### **3. Conclusion**

The advantageous impacts of probiotics have been illustrated in numerous diseases. One of the major mechanisms of probiotic activity is through the control of resistant reaction. A few of the prevalently utilized probiotic microorganisms are *Lactobacillus rhamnosus*, *Lactobacillus reuteri*, bifidobacteria and certain strains of *Lactobacillus casei, Lactobacillus acidophilus*-group, *Bacillus coagulans*, *Escherichia coli* strain Nissle 1917, certain enterococci, particularly *Enterococcus faeciumSF68*,

**95**

**Author details**

Ali Hossein Khani1

and Ayoub Farhadi4

University, Guilan, Iran

*The* Bifidobacterim bifidum *(BIB2) Probiotic Increased Immune System Factors in Men Sprint…*

and the yeast *Saccharomyces boulardii*. Bacterial spore formers, generally of the class Bacillus dominate the scene. These probiotics are included to foods, especially

As shown below a number of mechanisms are thought to be associated with

1.Production of inhibitory substances such as H2O2, bacteriocins, organic acids,

The results of this study show that the probiotic *Bifidobactrium bifidum* BIB2) juice supplementation can significantly affect some immune system factors including IgA, IgM, lymphocytes, monocytes and CD4 cell count in sprint athletes

fermented drain items, either separately or in combinations.

2.Blocking of adhesion sites for pathogenic bacteria.

5.Modulate inflammatory immune responses [45].

3.Compete with and inhibit growth of potential pathogens,

4.Degradation of toxins as well as the blocking of toxin receptors,

\*, Seyed Milad Mousavi Jazayeri2

Central Tehran Branch, Islamic Azad University, Tehran, Iran

Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

\*Address all correspondence to: h.khani.ali@gmail.com

provided the original work is properly cited.

Sari Agricultural Sciences and Natural Resources University, Sari, Iran

1 Department of Cellular and Molecular Biology, Young Researchers and Elite Club,

2 Department of Microbiology, Science and Research Branch, Islamic Azad

3 Department of Microbiology, Faculty of Advanced Sciences and Technology,

4 Laboratory for Molecular Cytogenetic, Faculty of Animal Sciences and Fisheries,

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

, Elahe Ebrahimi3

*DOI: http://dx.doi.org/10.5772/intechopen.84222*

probiotic beneficial effects:

compared to control group.

and so on.

and the yeast *Saccharomyces boulardii*. Bacterial spore formers, generally of the class Bacillus dominate the scene. These probiotics are included to foods, especially fermented drain items, either separately or in combinations.

As shown below a number of mechanisms are thought to be associated with probiotic beneficial effects:


The results of this study show that the probiotic *Bifidobactrium bifidum* BIB2) juice supplementation can significantly affect some immune system factors including IgA, IgM, lymphocytes, monocytes and CD4 cell count in sprint athletes compared to control group.

## **Author details**

*Nutraceuticals - Past, Present and Future*

that was consistent with our results [43]. In the present study in the athletes who drank juice containing the probiotic, the IgM was significantly higher than control group (**Figure 6** and **Table 2**). Probiotic bacteria in reaction with macrophage cells in tight junctions of epithelial cells, immune cells and dendritic cells led to the development of immune function, then macrophages and dendritic cells also generate immune responses through it. The dendritic cells spread their teeth between intestinal epithelial cells in the intestinal wall and use the probiotics to regulate immune function. The reaction of probiotic with intestinal epithelial cells induces the secretion of antimicrobial factors and cytokines and leading to activation of B and T lymphocytes in the lymphoid tissue of the gastrointestinal tract [6, 44, 32]

*Comparsion the means of lymphocyte percentage between test and control group (n = 3) in sprint athletes.*

Before test 32.7 ± 5.6a,\*\* 34.3 ± 4.8a First month 37.4 ± 6.4a 33.6 ± 7.2b Second month 35.5 ± 5.7a 33.1 ± 6.4b Third month 36.2 ± 7.3a 33.7 ± 6.8b P-value <0.05

*Comparsion the means of monocyte percentage between test and control group (n = 3) in sprint athletes.*

**Time Lymphocyte (%)**

*\*\*Means with same superscript letters in each row are significantly (P < 0.05) different.*

**Time Monocyte (%)**

Before test 3.85 ± 0.36\*\* 3.78 ± 0.42\* First month 4.30 ± 0.65\* 3.77 ± .025\* Second month 5.01 ± 0.42\* 3.78 ± 0.24\* Third month 5.60 ± 1.2 3.91 ± 0.90\* P-value <0.05

*\*\*Means with same superscript letters in each row are significantly (P < 0.05) different.*

**Test group Control group Means ± SD\* Means ± SD**

**Test group Control group Means ± SD\* Means ± SD**

The advantageous impacts of probiotics have been illustrated in numerous diseases. One of the major mechanisms of probiotic activity is through the control of resistant reaction. A few of the prevalently utilized probiotic microorganisms are *Lactobacillus rhamnosus*, *Lactobacillus reuteri*, bifidobacteria and certain strains of *Lactobacillus casei, Lactobacillus acidophilus*-group, *Bacillus coagulans*, *Escherichia coli* strain Nissle 1917, certain enterococci, particularly *Enterococcus faeciumSF68*,

**94**

(**Tables 4** and **5**).

*\*Standard division.*

*\*Standard division.*

**Table 4.**

**Table 5.**

**3. Conclusion**

Ali Hossein Khani1 \*, Seyed Milad Mousavi Jazayeri2 , Elahe Ebrahimi3 and Ayoub Farhadi4

1 Department of Cellular and Molecular Biology, Young Researchers and Elite Club, Central Tehran Branch, Islamic Azad University, Tehran, Iran

2 Department of Microbiology, Science and Research Branch, Islamic Azad University, Guilan, Iran

3 Department of Microbiology, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

4 Laboratory for Molecular Cytogenetic, Faculty of Animal Sciences and Fisheries, Sari Agricultural Sciences and Natural Resources University, Sari, Iran

\*Address all correspondence to: h.khani.ali@gmail.com

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Laboratory Course. Ontario, Canada: The University of Western Ontario; 2012

[16] Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology. Elsevier Health Sciences. 2014

[17] Spence L, Brown WJ, Pyne DB, Nissen MD, Sloots TP, McCormack JG, et al. Incidence, etiology, and symptomatology of upper respiratory illness in elite athletes. Medicine and Science in Sports and Exercise. 2007;**39**(4):577

[18] Lenoir-Wijnkoop I, Sanders ME, Cabana MD, Caglar E, Corthier G, Rayes N, et al. Probiotic and prebiotic influence beyond the intestinal tract. Nutrition Reviews. 2007;**65**(11):469-489

[19] Wanke M, Szajewska H. Lack of an effect of Lactobacillus reuteri DSM 17938 in preventing nosocomial diarrhea in children: A randomized, double-blind, placebo-controlled trial. The Journal of Pediatrics. 2012;**161**(1):40-43. e1

[20] Servin AL. Antagonistic activities of lactobacilli and bifidobacteria against microbial pathogens. FEMS Microbiology Reviews. 2004;**28**(4):405

[21] Gourbeyre P, Denery S, Bodinier M. Probiotics, prebiotics, and synbiotics: Impact on the gut immune system and allergic reactions. Journal of Leukocyte Biology. 2011;**89**(5):685

[22] Biswas D, Wideman NE, O'Bryan CA, Muthaiyan A, Lingbeck JM, Crandall PG, et al. Pasteurized blueberry (*Vaccinium corymbosum*) juice inhibits growth of bacterial pathogens in milk but allows survival of probiotic bacteria. Journal of Food Safety. 2013;**32**(2):204

[23] Arunachalam KD. Role of bifidobacteria in nutrition, medicine and technology. Nutrition Research. 1999;**19**(10):1559

[24] Kotani Y, Shinkai S, Okamatsu H, Toba M, Ogawa K, Yoshida H, et al. Oral intake of *Lactobacillus pentosus* strain b 240 accelerates salivary immunoglobulin A secretion in the elderly: A randomized, placebocontrolled, double-blind trial. Immunity and Ageing. 2010;**7**:11

[25] Glaser R, Kiecolt-Glaser JK. Handbook of Human Stress and Immunity. The University of Michigan: Academic Press; 1994

[26] Gareau MG, Sherman PM, Walker WA. Probiotics and the gut microbiota in intestinal health and disease. Nature Reviews Gastroenterology and Hepatology. 2010;**7**(9):503

[27] Sharma R, Kapila R, Kapila S. Probiotics as anti-immunosenescence agents. Food Reviews International. 2013;**29**(2):201

[28] Lee J-W, Shin J-G, Kim EH, Kang HE, Yim IB, Kim JY, et al. Immunomodulatory and antitumor effects in vivo by the cytoplasmic fraction of *Lactobacillus casei* and *Bifidobacterium longum*. Journal of Veterinary Science. 2004;**5**(1):41

[29] West N, Pyne D, Peake J, Cripps A. Probiotics, immunity and exercise: A review. Exercise Immunology Review. 2009;**15**(107):e26

[30] Ohashi Y, Ushida K. Healthbeneficial effects of probiotics: Its mode of action. Animal Science Journal. 2009;**80**(4):361

[31] Yamada Y, Aoyama A, Tocco G, Boskovic S, Nadazdin O, Alessandrini A, et al. Differential effects of denileukin diftitox IL-2 immunotoxin on NK and regulatory T cells in nonhuman primates. The Journal of Immunology. 2012;**188**(12):6063

[32] Golden-Mason L, Cox AL, Randall JA, Cheng L, Rosen HR.

**96**

*Nutraceuticals - Past, Present and Future*

[1] Margonis K, Fatouros IG, Jamurtas AZ, Nikolaidis MG,

Medicine. 2007;**43**(6):901-910

2006;**101**(6):1664-1672

[3] Prasanna P, Grandison AS, Charalampopoulos D. Bifidobacteria in milk products: An overview of physiological and biochemical properties, exopolysaccharide production, selection criteria of milk products and health benefits. Food Research International. 2014;**55**:247-262

[4] Gareau MG, Sherman PM, Walker WA. Probiotics and the gut microbiota in intestinal health and disease. Nature Reviews Gastroenterology and Hepatology.

[5] Sanders ME, Guarner F, Guerrant R, Holt PR, Quigley EM, Sartor RB, et al. An update on the use and investigation of probiotics in health and disease. Gut.

2010;**7**(9):503-514

2013;**62**(5):787-796

[6] Kekkonen R, Vasankari T, Vuorimaa T, Ekblom T, Hintsa A, Kautiainen H, et al. The effect of probiotics on respiratory infections and gastrointestinal symptom episodes during the marathon training period in marathon runners. International Journal of Sport Nutrition and Exercise

Metabolism. 2007;**17**(4):352-363

[7] Cox AJ, Pyne DB, Saunders PU, Fricker PA. Oral administration of the probiotic Lactobacillus fermentum

[2] Fry AC, Schilling BK, Weiss LW, Chiu LZ. β2-Adrenergic receptor downregulation and performance decrements during high-intensity resistance exercise overtraining. Journal of Applied Physiology.

Douroudos I, Chatzinikolaou A, et al. Oxidative stress biomarkers responses to physical overtraining: Implications for diagnosis. Free Radical Biology and VRI-003 and mucosal immunity in endurance athletes. British Journal of Sports Medicine. 2010;**44**(4):222-226

[8] Bishop N, Gleeson M. Acute and chronic effects of exercise on markers of mucosal. Immunity.

[9] Svendsen IS, Hem E, Gleeson M. Effect of acute exercise and hypoxia on markers of systemic and mucosal immunity. European Journal of Applied

[10] Reid V, Gleeson M, Williams N, Clancy R. Clinical investigation of athletes with persistent fatigue and/or recurrent infections. British Journal of Sports Medicine. 2004;**38**(1):42-45

[11] Cox AJ, Gleeson M, Pyne DB, Callister R, Hopkins WG, Fricker PA. Clinical and laboratory evaluation of upper respiratory symptoms in elite athletes. Clinical Journal of Sport Medicine. 2008;**18**(5):438-445

[12] Nieman DC. Is infection risk linked to exercise workload? Medicine and Science in Sports and Exercise. 2000;**32**(7 Suppl):S406-S411

[14] Moreira A, Mortatti AL, Arruda AF, Freitas CG, de de Arruda M, Aoki MS. Salivary IgA response and upper respiratory tract infection symptoms during a 21-week competitive season in young soccer players. The Journal of Strength & Conditioning Research.

[15] Barbeau ML. Transactional Distances in an Online Histology

2014;**28**(2):467-473

2014;**3**(2):3

[13] Barret S, Storey A, Harrison M. The effect of exercise mode on salivary IgA secretion in high level triathletes. Journal of Science and Cycling.

2009;**1**(14):4444-4456

Physiology. 2016:1-11

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[42] Sakai F, Hosoya T, Ono-Ohmachi A, Ukibe K, Ogawa A, Moriya T, et al. *Lactobacillus gasseri* SBT2055 induces TGF-β expression in dendritic cells and activates TLR2 signal to produce IgA in the small intestine. PLoS One. 2014;**9**(8):e105370

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**99**

**Chapter 6**

**Abstract**

supplement.

bioactive compounds

**1. Introduction**

Marine Sources

*Charu Gupta and Dhan Prakash*

Nutraceuticals from Microbes of

Therapeutic compounds can be derived from various natural sources like plants,

animals, marine organisms, and microorganisms. Although the marine biota accounts for around 50% of the total world biodiversity, but their potential as a rich source of bioactive products and their applications in both pharmaceutical and nutraceutical industries have only recently been identified through several scientific studies. Marine biotechnology is an upcoming area that involves about the study of marine microorganisms and animals including algae, sponges, and coral as a novel source of bioactive substances that can be used in the treatment of various human diseases like cancer, anemia, diarrhea, obesity, diabetes, atopic dermatitis, Crohn's disease, etc. They are also potential sources of natural antioxidants, colors, immunosuppressants, enzyme inhibitors, hypocholesterolemic agents, vitamins, enzymes, and antibiotics. However, marine microorganisms have not yet been given the attention they deserve and a very limited scientific data is available on bioactive potential of marine microorganisms. There is still scope for a higher magnitude of research and investigation to explore the potential of both marine organisms and marine microorganisms as producers of novel drugs. This chapter deals with the exploitation of microbes from marine sources as potential sources for various nutraceuticals and their possibilities for applications in variety of diseases and as functional food

**Keywords:** microbes, nutraceuticals, marine organisms, functional food,

It is well-known that more than 70% of our planet's surface is covered by oceans. Experts estimate that the biological diversity in marine environment is higher than in tropical rain forests. Marine water contains enormous amounts of biodiversity which makes it as a source of huge amounts and wide varieties of novel bioactive compounds. The majority of the marine microbiota is soft bodied and follows a sedentary life style, thus requiring the other means of defense systems mainly by producing certain biochemical compounds that are generally toxic to the other animals. These toxic substances also aid them in detecting their harmful predators, and help them to protect themselves from their competitors or they can even paralyze their enemies. The biodiversity of marine microflora is overwhelming and there is an urgent need to explore and exploit their potential as biotherapeutic agents. These biotherapeutic compounds are usually synthesized as secondary metabolites by the marine microflora and fauna. The disadvantage is that since these natural

## **Chapter 6**

*Nutraceuticals - Past, Present and Future*

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