Connie: My dear friends, thank you for joining us on this beautiful Saturday evening. It’s great to have you here with us. Also here with me, is our old friend, Dr. Leonard Hofstadter, who has been an editor of scientific journals for a long time. Thank you for being here, Dr. Hofstadter.

Dr. Hofstadter: Thanks for inviting me, Connie. Good evening, everyone. I’m very excited to be here.

Connie: Probiotics have many beneficial effects on human health. Dr. Hofstadter has explained the mechanism of these benefits from various aspects to us in previous episodes. In the last program, we discussed the contribution of probiotics in lowering cholesterol, preventing and treating cancer, and affecting irritable bowel syndrome through different mechanisms. And we have also talked about their beneficial effects and mechanisms in cancer therapeutics. But of course, probiotics can do much more. So in today’s episode, we are going to further explore their benefits. Where should we start, Dr. Hofstadter?

Dr. Hofstadter: Let’s start with allergies. I feel that in modern society, allergy has become a big problem. Over the past 50 to 60 years, the incidence rate of allergies in western society has greatly increased.

Connie: Yeah, I think so, allergies are bothering more and more people. How did it come about?

Dr. Hofstadter: In short, allergy is the response of the immune system to foreign substances. There are two types of allergies, antibody-mediated allergy, and cell-mediated allergy. Allergic reactions occur when a person is exposed to higher doses of stimulation, you know, those foreign substances called allergens, usually proteins. Allergens enter the human body through a variety of ways, such as breathing, eating and skin contact, or during insect bites, and can reach the immune system.

Connie: Tell us some factors of allergic diseases?

Dr. Hofstadter: There can be genetic factors, the correlation of allergen exposure, host and other environmental stimuli, such as intestinal microflora, and infectious factors. Taking genetic factors as an example, atopy is a genetic tendency that occurs in children or adolescents. When foreign bodies contact the immune system, they will induce the production of IgE antibodies and produce symptoms such as asthma, rhinoconjunctivitis, and atopic dermatitis.

Connie: As far as I know, some studies have shown that the occurrence of allergies and related diseases is due to insufficient exposure to environmental microorganisms. What do probiotics have to do here?

Dr. Hofstadter: It’s actually not difficult to understand. Allergy is related to the change of the proportion of T-helper 1 cytokines. And T-helper 2 cytokines stimulate the production of IgE and release different interleukin. The consumption of probiotics changes the GI microenvironment by changing the local microflora and the production of cytokines. Studies have shown that probiotics change toll-like receptors and various recognition proteins in the intestinal mucosa, stimulate dendritic cells and T-helper 1 cytokine response, and inhibit T-helper 2 response.

Connie: I see. Some experts said that probiotics play an active role in the treatment of allergic diseases. What is the mechanism behind it?

Dr. Hofstadter: In short, probiotics play a therapeutic role by developing mucosal barriers and stimulating the immune system. Some studies on atopic eczema and food allergy have shown that probiotics play an important role in reducing inflammation in allergic reactions.

Connie: I’ve heard that supplementing infants with Lactobacillus rhamnosus GG can halve the incidence of eczema.

Dr. Hofstadter: That’s right. In newborn infants, the first batch of bacteria occupying the GI tract can establish a stable niche. These bacteria are very important for regulating the immune system, so they also play an important role in the development of atopic diseases. Studies on atopic children have shown that probiotics can up-regulate anti-inflammatory cytokines such as interleukin-10. The symptoms of eczema can be reduced by adding Lactobacillus GG to the diet of newborns with hydrolyzed whey formula.

Connie: Can you summarize the various mechanisms by which probiotics affect allergies and change immune response?

Dr. Hofstadter: Sure. Probiotics can stimulate the specific response of B cells and T cells to allergens and mucosal IgA levels, so as to reduce the impact of allergic diseases. Other studies have also suggested that the connection between bacteria and host can stimulate the growth of T regulatory cells, produce cytokines such as interleukin-10, and change growth factors- β. Toll-like receptors, gene networks, various signaling molecules, and elevated IgA levels are involved in these interactions, making them quite complex.

Connie: In addition to allergen stimulation in the environment, some foods can also cause allergic reactions. How do probiotics deal with food allergies?

Dr. Hofstadter: Right. Food allergy is pretty common too. Probiotics can treat food allergy by increasing the internal barrier of the intestine, reducing intestinal wall inflammation, and reducing the concentration of IgE in serum. I mean, both the non-immune and immune defense barriers of the intestine can be affected by probiotics. This can lead to increased inflammation in food allergies. Probiotics also help alleviate allergies associated with milk proteins because they can degrade proteins in milk into smaller peptides or amino acids.

Connie: I get it. And next, I wanted to talk about Antibiotic-associated diarrhea, which is caused by the imbalance of gastrointestinal flora caused by antibiotics. This disease can start with mild diarrhea and, if not treated, may further lead to a life-threatening disease that is named pseudomembranous colitis. What antibiotics are associated with this disease?

Dr. Hofstadter: Antibiotics that act on bacteria, such as adriamycin, clindamycin, and cephalosporin, are associated with a higher possibility of antibiotic-associated diarrhea. In most cases, the causes behind diarrhea are unclear, although, in patients with the most severe forms and persistent diseases, such as people with inflammatory bowel disease, cystic fibrosis, and cancer, the pathogenic factor is Clostridium difficile.

Connie: Good that the use of antibiotics is controlled. It has been observed that the use of probiotics and their fermented products such as yogurt reduces the frequency of antibiotic-associated diarrhea. Any theory supports this result?

Dr. Hofstadter: Yeh, there is the theory that the occurrence of antibiotic-associated diarrhea is due to microbial imbalance caused by the use of antibiotics, and the interference of probiotics also changes the intestinal microflora. Lactobacillus Acidophilus, L.bulgaricus, L.rhamnosus, and Saccharomyces Boulardii have been used to inhibit antibiotic-associated diarrhea.

Connie: Diarrhea is common in infants. Nosocomial diarrhea is a major problem among children all over the world. Can probiotics help alleviate this problem?

Dr. Hofstadter: It has been reported that Streptococcus thermophilus, Lactobacillus rhamnosus GG, and Bifidobacterium are effective for treating neonatal diarrhea. They are mainly used to eliminate acute diarrhea. Probiotics commonly used in the treatment of children’s diarrhea include lactobacillus, Lactobacillus casei, Lactobacillus Leipzig, Bifidobacterium, Brucella, and Streptococcus thermophilus.

Connie: As we have learned before, probiotics also compete with pathogens for binding sites with the inner wall of the intestine to prevent infection. In addition, probiotics reduce the growth of pathogens by producing some metabolites like bacteriocin. Have any studies used these mechanisms and get good results?

Dr. Hofstadter: Of course. Several studies have shown that probiotics can prevent pathogens from attaching to intestinal cells. This blockade is thought to intervene by increasing the expression of intestinal mucin MUC2 and MUC3. In a meta-analysis of 21 studies that include 4780 children and adults, Streptococcus brucelli reduced the risk of antibiotic-associated diarrhea from 19 percent to 8.5 percent, with a risk ratio of 0.47. Moreover, one study included 82 randomized clinical trials using different probiotics and observed a hazard ratio of 0.58 for antibiotic-associated diarrhea. Researchers found that combining probiotics can also reduce the incidence of diarrhea caused by Clostridium difficile.

Connie: Sounds promising. A group of diseases described as chronic inflammation of the GI tract have also received a lot of attention in recent years. Can you remind us what they are and what harm they can bring us?

Dr. Hofstadter: Oh they are inflammatory bowel disease, mainly Crohn’s disease and ulcerative colitis. Crohn’s disease can be seen anywhere along the intestinal wall, mainly damaging the lower part of the small intestine. The damage to the colon is called ulcerative colitis. In ulcerative colitis, inflammation is limited to the intestinal epithelium, while in Crohn’s disease, the inflammation affects the entire intestinal wall. Some common symptoms in both cases include abdominal pain, weight loss, intestinal ulcer, bleeding, and diarrhea, but intestinal wall narrowing, fistula and fissure are common in Crohn’s disease.

Connie: We know that the use of specific strains of lactic acid bacteria has been reported to significantly enhance the signs of inflammatory bowel disease, cystitis, and ulcerative colitis. How does that happen?

Dr. Hofstadter: Lactic acid bacteria reduce intestinal pH by producing organic acids. Organic acids can enhance intestinal fluidity and relieve constipation. The production of short-chain fatty acids has a positive effect on inflammatory bowel disease, mainly acetic acid, butyric acid, and propionic acid.

Connie: Oh ok. The consumption of probiotics can promote the production of short-chain fatty acids. So do you think it’s possible to treat inflammatory bowel disease by taking probiotics?

Dr. Hofstadter: In fact, intestinal microflora or probiotics have a positive regulatory effect on inflammatory intestinal diseases. Inflammatory bowel disease can be treated by supplementing probiotics, prebiotics, and synbiotics. short-chain fatty acids are considered to play a crucial role in maintaining colonic homeostasis. It is well known that they can improve colon function and have anti-inflammatory effects. So you know, by eating more dietary fiber alone or with probiotics, the body can promote the production of single-chain fatty acids, and there you could have an effective remedy.

Connie: That’s interesting. At present, many diseases are closely related to the oxidation reaction in the body. People are also keen to find effective and safe antioxidant methods. What are some serious consequences of oxidation?

Dr. Hofstadter: Right. During normal metabolism, free radicals are produced in the human body. But when our cells are exposed to foreign compounds in food and the external environment, the production of free radicals will increase significantly. Free radicals cannot be effectively neutralized by the antioxidant system of organisms. The oxidation of membrane lipids, enzymes, proteins and DNA leads to fatal changes, such as cell death. Free radicals cause damage at the cellular and subcellular levels, which will lead to serious consequences, like the development of cancer, heart disease, allergy, arteriosclerosis, and many other diseases. Patients with Alzheimer’s disease have also been detected of great damage to basic molecules in the brain caused by oxidation.

Connie: Now I really want to know what antioxidants are out there? Can you list some common ones?

Dr. Hofstadter: Vitamin C, vitamin E, carotenoids, phytoestrogens, folic acid, flavonoids, and selenium are all antioxidants.

Connie: It’s well known that probiotics can capture reactive oxygen species. Does this mean that probiotics are also potential antioxidants?

Dr. Hofstadter: You’re right. Several bacteria found in fermented milk have antioxidant activity and have a positive impact on human health. Clinical studies also support the antioxidant activity of goat fermented milk with Lactobacillus fermentum. Lactobacillus bulgaricus and Streptococcus thermophilus inhibit lipid peroxidation by scavenging hydroxyl or hydrogen peroxide. You know, yogurt can enhance the antioxidant capacity of lipoprotein, improve the antioxidant activity of blood, and reduce the levels of oxidized low-density lipoprotein and peroxylipoprotein.

Connie: I’m going to have a yogurt later tonight. Lactic acid bacteria also exist in the human intestines and stomach. What role do they play in antioxidation?

Dr. Hofstadter: They can produce some antioxidant factors in the GI tract. These bacteria eliminate excess oxygen free radicals by producing superoxide dismutase or glutathione. Various studies continue to use lactic acid bacteria as an option for food supplements to improve the antioxidant activity of the human body.

Connie: Throughout all these episodes so far, we have basically discussed most of the beneficial effects of probiotics on humans. And let’s save more discussions for next week. So much for our content today. Thank you everyone for listening. I hope you enjoyed today’s show. And thank you, Dr. Hofstadter for providing us with your great insight. We will see you next week.

Dr. Hofstadter: Thanks for having me. I hope we will see you next time.