200 ◾ Fundamental Food Microbiology
pathogenic bacteria from circulation, and activation of macrophages to produce cytokines TNF-α,
IL-6, IL-12, and IL-18 to induce immune responses. Humoral response includes increased production of mucosal secretory IgA to prevent attachment of pathogens and antiviral IgG to eliminate viral infection, such as during rotavirus-induced diarrhea.
Reducing Allergic Diseases
Establishment of normal gut flora, which starts after birth and continues up to two years of age, may
be important in the development in later life of a counter-regulatory ability against several specific
immune responses. The normal flora of the GI tract enters the body through food, water, air, and
other environmental sources. Raising infants in an oversanitary environment and feeding semisterile
processed foods may interfere with the establishment of normal microflora in the GI tract. This may
cause the immune system of infants to develop an inflammatory response to many food antigens.
Probiotics containing beneficial gut bacteria can have a suppressive effect to such reaction by stimulating the production of anti-inflammatory cytokines and reducing allergic reactions in sensitive
individuals. Many studies suggest that infants with atopic diseases (allergies) have lower counts of
lactobacilli, bifidobacteria, and Bacteriodes; however, further experimental evidences are needed to
establish a strong relationship between gut microbiota and atopic diseases in children. 4
Bioengineered Probiotics
The antimicrobial effect of probiotics is generic and redundant, and sometimes the effect is unsatisfactory. Thus probiotics are engineered to express foreign proteins usually from the pathogen of
interest to create a competitive environment to exclude the target pathogen from interacting with
the host cells. 9,10 The concept started in the last decade when scientists from Stanford University
expressed a HIV-1 surface protein receptor (Gp120) on Lactobacillus jensenii. 11 This recombinant
Lactobacillus expressing Gp120 interacted with the host T cell marker CD4 and thus was able to
prevent direct viral interaction with the cells in the genital tract of the host. A similar approach
was used to develop a toxin receptor mimicry system in a probiotic to combat enteric infections. A
toxin receptor, such as an oligosaccharide from a host cell, was expressed in probiotic bacteria and
during infection; bacterial toxins bound strongly to the receptor expressed on the probiotic surface
thus prevented toxic effects and protected host. This approach was able to control infection caused
by enteric pathogens Escherichia coli, Vibrio cholera, Clostridium difficile, and Clo. perfringens in
animal models. Helicobacter pylori infection was also reduced by expressing urease, an adhesion
factor in host gastric cells, in probiotic bacteria, creating a competitive environment to exclude
Hel. pylori colonization. Similarly, expression of Listeria adhesion protein on probiotics was able
to reduce Listeria monocytogenes infection. A probiotic expressing Esc. coli fimbrial antigen also
provided protection against this pathogen.
Probiotics as Vaccine Carriers for infectious Agents
Many probiotics’ natural habitat is the intestine; thus they are an ideal delivery vehicle for a vaccine agent to the mucosal surface. 12,13 Probiotics were engineered to deliver varieties of antigens.
The first recombinant probiotic oral vaccine was developed by expressing the tetanus toxin antigen
in Lactococcus lactis to protect the host against tetanus. A Lactococcus lactis strain was engineered
pathogenic bacteria from circulation, and activation of macrophages to produce cytokines TNF-α,
IL-6, IL-12, and IL-18 to induce immune responses. Humoral response includes increased production of mucosal secretory IgA to prevent attachment of pathogens and antiviral IgG to eliminate viral infection, such as during rotavirus-induced diarrhea.
Reducing Allergic Diseases
Establishment of normal gut flora, which starts after birth and continues up to two years of age, may
be important in the development in later life of a counter-regulatory ability against several specific
immune responses. The normal flora of the GI tract enters the body through food, water, air, and
other environmental sources. Raising infants in an oversanitary environment and feeding semisterile
processed foods may interfere with the establishment of normal microflora in the GI tract. This may
cause the immune system of infants to develop an inflammatory response to many food antigens.
Probiotics containing beneficial gut bacteria can have a suppressive effect to such reaction by stimulating the production of anti-inflammatory cytokines and reducing allergic reactions in sensitive
individuals. Many studies suggest that infants with atopic diseases (allergies) have lower counts of
lactobacilli, bifidobacteria, and Bacteriodes; however, further experimental evidences are needed to
establish a strong relationship between gut microbiota and atopic diseases in children. 4
Bioengineered Probiotics
The antimicrobial effect of probiotics is generic and redundant, and sometimes the effect is unsatisfactory. Thus probiotics are engineered to express foreign proteins usually from the pathogen of
interest to create a competitive environment to exclude the target pathogen from interacting with
the host cells. 9,10 The concept started in the last decade when scientists from Stanford University
expressed a HIV-1 surface protein receptor (Gp120) on Lactobacillus jensenii. 11 This recombinant
Lactobacillus expressing Gp120 interacted with the host T cell marker CD4 and thus was able to
prevent direct viral interaction with the cells in the genital tract of the host. A similar approach
was used to develop a toxin receptor mimicry system in a probiotic to combat enteric infections. A
toxin receptor, such as an oligosaccharide from a host cell, was expressed in probiotic bacteria and
during infection; bacterial toxins bound strongly to the receptor expressed on the probiotic surface
thus prevented toxic effects and protected host. This approach was able to control infection caused
by enteric pathogens Escherichia coli, Vibrio cholera, Clostridium difficile, and Clo. perfringens in
animal models. Helicobacter pylori infection was also reduced by expressing urease, an adhesion
factor in host gastric cells, in probiotic bacteria, creating a competitive environment to exclude
Hel. pylori colonization. Similarly, expression of Listeria adhesion protein on probiotics was able
to reduce Listeria monocytogenes infection. A probiotic expressing Esc. coli fimbrial antigen also
provided protection against this pathogen.
Probiotics as Vaccine Carriers for infectious Agents
Many probiotics’ natural habitat is the intestine; thus they are an ideal delivery vehicle for a vaccine agent to the mucosal surface. 12,13 Probiotics were engineered to deliver varieties of antigens.
The first recombinant probiotic oral vaccine was developed by expressing the tetanus toxin antigen
in Lactococcus lactis to protect the host against tetanus. A Lactococcus lactis strain was engineered