Connie: Good evening, dear friends. Thank you for tuning in to our program. It’s great to have you here with us. Today, we invited Dr. Hofstadter to our program. Thank you for joining us today, Dr. Hofstadter.
Dr. Hofstadter: Thanks for having me. Glad to be here. Hello, everyone.
Connie: In the past decades, probiotic strains have gained high interest as a supplement for both humans and animals, as people expect that probiotics might play an important role in overall health improvement. And after numerous dedicated research, the beneficial health effects of probiotics were confirmed for several gut and metabolic disorders including obesity, diabetes, gastroenteritis, et cetera. And today, we are going to discuss some interesting facts about probiotics.
Dr. Hofstadter: At the very beginning, I want to give a brief overview of probiotics. Probiotics are a type of active microorganisms that are beneficial to the host by colonizing the host’s body and changing the composition of a certain part of the host’s flora, by adjusting the host mucosa and system immune function or by adjusting the balance of the intestinal flora. They can promote nutrient absorption and maintain intestinal health. So in short, they are single microorganisms or mixed microorganisms with a clear composition that are beneficial to health.
Connie: In a nutshell, probiotics are the live microorganisms which when administered in an adequate amount confer health benefits to the host.
Dr. Hofstadter: Exactly.
Connie: What are the features of these probiotics?
Dr. Hofstadter: Well, there are several hallmark features. The first one would be that probiotics cannot tolerate gastric and bile salts. Secondly, they adhere to the host intestinal epithelial cells. Thirdly, probiotics can remove or reduce the adhesion of pathogenic bacteria. The next one would be probiotics can inhibit pathogenic bacteria. The last feature is that they are safe and non-pathogenic. Because of all these features, and their ability to restore a healthy human gut microbial ecosystem, a new class of probiotics, which is called bio-therapeutic probiotics, has been developed.
Connie: Some experiments have verified that these beneficial bacteria could be successfully administered for the prevention or treatment of a variety of pathological, metabolic, and neural disorders. So what are some benefits of probiotics to the human body?
Dr. Hofstadter: First of all, probiotics can synthesize digestive enzymes. Together with the digestive enzymes synthesized by the animal body, they participate in the digestion of nutrients in the intestine, stimulate the animal body to secrete digestive enzymes, reduce the depth of small intestinal crypts, increase the height of villi, increase the surface area of the small intestine, and they can promote intestinal nutrient absorption. Next, probiotics can improve the body’s immunity. That is mainly because the structure probiotics such as peptidoglycan, lipoteichoic acid, and other components can be used as antigens to directly exert immune activation effects, or through autocrine immune activators to stimulate the host immune system, and then you know, they will be able to enhance the immunity of animals and the activity of the body’s innate immune cells as well as natural killer cells. Probiotics also can activate dendritic cells, then stimulate the body to produce cytokines, and stimulate B cells to secrete antibodies. Moreover, probiotics can stimulate the intestinal tract to produce secretory globulin A to protect the health of the body. And finally, probiotics can improve the body’s antioxidant level. But I’m sure this is not the last benefit that probiotics can have on the human body.
Connie: That’s really impressive how much probiotics can benefit us. Just to expand a little. For the last benefit you mentioned, Why is it important to remove oxides from the body?
Dr. Hofstadter: As is known to all, oxides in the body, such as oxygen free radicals and hydroxyl free radicals, contain unpaired electrons, which are prone to redox reactions. Excessive oxides in the body will cause the body to produce oxidative damage. There is an antioxidant system in the body, which constantly removes the oxides synthesized by the body and maintains the dynamic balance of the oxides.
Connie: I see. In recent years, probiotics, as biological therapy, have attracted extensive interest in the treatment of different metabolic and brain diseases. Based on what you just mentioned, beneficial intestinal microbiota can produce several metabolites that have direct and indirect effects on host pathophysiology. Regulating the intestinal microbiota through probiotic intervention is becoming a new frontier for the possible management of a variety of clinical scenarios. Probiotic management balances the intestinal bacterial population and promotes its beneficial metabolism. What is a good example of therapeutic probiotics?
Dr. Hofstadter: I would say it is the use of probiotics in the treatment of foodborne diseases. We all know that common food poisoning, intestinal infectious diseases, zoonotic infectious diseases, parasitic diseases, and diseases caused by chemical toxic and harmful substances all belong to the category of foodborne diseases. Probiotics can reduce the degree of foodborne diseases by enhancing patients’ intestinal immune function, interfering with pathogen infection and maintaining the activity of intestinal beneficial microorganisms.
Connie: You sure just added more benefits. So we know that foodborne diseases can also be treated by some traditional methods. What are their drawbacks compared to probiotic therapy?
Dr. Hofstadter: Right. I think you mean different physical, chemical, and biological methods when you said traditional treatment methods. Although these methods are effective in the treatment of foodborne diseases, they are not 100 percent effective. And these methods also increase side effects. So I would say the most promising treatment of foodborne diseases depends on probiotics.
Connie: So, have there been any probiotics applied in foodborne diseases?
Dr. Hofstadter: Yeah. Lactic acid bacteria, especially species of Lactobacillus and Bifidobacterium, are the most communal probiotic strains used in milk fermentation. Lactic acid bacteria refer to a class of non-spore-free, Gram-stain-positive bacteria whose main product of fermented sugar is lactic acid. Lactic acid bacteria are the most common probiotics, which have been widely used and are considered safe for humans and animals.
Connie: That sounds great. We have just listed countless benefits of probiotics. Now I want to explore this more in-depth. How do probiotics work? What is the mechanism behind that enables probiotics to fight against infectious diseases like foodborne diseases?
Dr. Hofstadter: Well. To put it simply, probiotics prevent infectious disease by four major proposed mechanisms of action, including competition, antimicrobial secretions, increased intestinal barrier function and immunomodulation.
Connie: Maybe we can start with “competition”. What does it mean?
Dr. Hofstadter: Yeah. You know that there are some interactions between bacteria and bacteria. These bacterial–bacterial interactions were mediated by competitions for nutrient absorption and bacterial adhesion sites. The competition between the bacteria causes exclusion or reduced growth of one bacterial species. Certain probiotic bacterial species cause inhibition of the establishment of pathogenic bacteria through the release of antimicrobial substances, specific adhesion of protein interaction with surface protein and mucin. In addition, probiotic bacteria can impose steric hindrance to the attachment of pathogenic bacteria at enterocyte pathogen receptors.
Connie: Can you be more specific and illustrate the point using some examples?
Dr. Hofstadter: Sure. For example, Lactobacillus acidophilus and Lactobacillus delbrueckii can competitively bind to Ferric hydroxide, rendering it unavailable for pathogens. Lactobacillus probiotic EcN releases siderophores that chelate and helps in the competitive uptake of iron ferrous or ferric via seven different uptake systems. Listeria infection in C2Bbe1 epithelial cell lines was observed to be inhibited by probiotic Lactobacillus due to combined production of antimicrobial acid and unidentified protein, whereas antimicrobial action of Bifidobacterium attributed to release of extracellular protein compound.
Connie: Interesting. So you mean that competition for the same receptor, degradation of carbohydrate receptor, receptor analogs, biofilm, and biosurfactant production can inhibit the settlement of pathogens in the host. Then what about “antimicrobial secretion”?
Dr. Hofstadter: Right. Probiotic bacteria can secrete various metabolites like organic acids including acetic or lactic acid, H2O2 and bacteriocins. The secretion can limit the growth of pathogens. Lactic acid bacteria increased the acidity of the surrounding medium by secreting lactic acid and acetic acid, making it unfavorable for the growth of various pathogens. Organic acid enters inside pathogen and dissociates in the cytoplasm, causing the breakdown of proton motive force leading to inhibition of nutrient transport and lysis of the cell.
Connie: Well. I have also found that probiotic bacteria can also produce some antibiotics. Some researches showed that Lactobacillus reuteri strain ATCC55730 can secrete broad-spectrum antibiotic reuterin, which is effective against Gram-positive and Gram-negative pathogen, viruses, fungi, yeast, and protozoa.
Dr. Hofstadter: That is true. What’s more impressive is that Lactobacillus bacteria can also produce pH and heat stable ribosomally synthesized bacteriocins, non-cytotoxic, bactericidal and bacteriostatic peptides. Unlike antibiotics, bacteriocins were very target specific in their action. Bacteriocins are antimicrobial peptides that disrupt cell walls by forming pores and block the synthesis of the cell wall of the target cell.
Connie: We all know that intestinal epithelial cells are composed of absorption cells, goblet cells and a small number of endocrine cells. It is a single-layer column, and the small intestine contains Paneth cells and undifferentiated cells. Besides, intestinal epithelial cells serve as the primary defense line and are foremost for probiotic action. What can probiotics do to increase intestinal barrier function?
Dr. Hofstadter: Well. Probiotics can enhance the intestinal barrier function mainly through stimulating the production of defensins peptides, improving immune response, improving the functionality of tight junctions, inhibiting epithelial cell apoptosis and generating cytoprotective molecules. I will give you some examples, like the application of Streptococcus thermophilus and Lactobacillus acidophilus. These two strains can significantly reduce the entero-invasive E. coli adhesion, invasion and physiological dysfunction in vitro experiments with HT-29 and Caco-2 cell lines. This occurs due to increased trans-epithelial resistance complemented with maintenance enhancement of tight junctions, phosphorylation and cytoskeleton. Also, Probiotic strains stimulate the release of small peptides known as defensins from epithelial cells, which can stimulate gut barrier function as well as inhibit the growth of bacteria, fungi, and viruses.
Connie: That is amazing. Now move on to our last topic, which is probiotics participate in immunomodulation.
Dr. Hofstadter: Yeah before we start the new discussion, I want to briefly introduce the mechanism of how pathogens are identified by the host. Pathogens have molecular patterns associated with their cell membrane which are recognized by pattern recognition receptors of the host. When the host pattern recognition receptor comes in contact with pathogen associated molecular pattern, it leads to induction of inflammatory response and activation of innate immunity. Various immune cells, including granulocytes, dendritic cells, macrophages, T cells and B cells, and cytokines, including tumor necrosis factor-α, interleukin 8, 6, 15, 1β, are involved in this response.
Connie: Does this have anything to do with the probiotics being involved in immune regulation?
Dr. Hofstadter: Well. Probiotic lactic acid bacteria are widely described to modulate innate as well as adaptive immunity, so that they can enhance immune response and prevent pathogenic infections. Lactic acid bacteria can cause induction of cytokine production, so they can activate innate as well as adaptive immune systems. L delbrueckii supplementation increased the anti-inflammatory cytokines in intestine interleukin 10 and tumor necrosis factor-β and decreased pro-inflammatory interleukin 8 cytokines in carp infected with Aeromonas hydrophila. Another example is that the application of L. Plantarum B2984 to Salmonella infected pigs encouraged the production of immunoglobulin M and immunoglobulin A.
Connie: I see. So, the probiotic application can directly re-establish the normal gut microflora. Thereby eliminating pathogens, reducing the incidence of infection, and maintaining healthy well-being without causing any ill effects such as antibiotic resistance.
Dr. Hofstadter: Exactly. This is the key message we are discussing.
Connie: Patients with foodborne diseases have a common feature, which is that they come on through eating behavior. So strengthening food hygiene supervision and management, advocating reasonable nutrition, controlling food pollution and improving food hygiene quality can most effectively prevent the occurrence of foodborne diseases. So much for our content today. Thanks, Dr. Hofstadter for providing such a meaningful discussion. And thanks, everyone for listening. We will continue our discussion next Saturday at the same time. See you then!
Dr. Hofstadter: Thanks, everyone. I hope we will see you next time.