Connie: Dear friends, thank you for joining us this Saturday night. And thank you, Dr. Hofstadter, for joining us again tonight.

Dr. Hofstadter: Thank you for inviting me. Good evening, everyone. It is quite nice to see you again. I’m very excited to be here.

Connie: In the last program, Dr. Hofstadter shared with us the basic information about probiotics and related categories. The development history of probiotics spans many years, and can be traced back to 800 years ago. With a more clear and in-depth understanding of probiotics, this term is gradually known by more people. Probiotics are simply referred to microorganisms or their components that are beneficial to the health of the host. Some prebiotics, synbiotics and epigenetics belong to the category of probiotics. Different kinds of microorganisms are used as probiotics with beneficial effects on human health. Most of these bacterial groups belong to lactic acid bacteria. Today, Dr. Hofstadter will discuss the potential applications of probiotics.

Dr. Hofstadter: Great. Let’s get started right away. The potential role of probiotics has attracted great attention from microbiologists, clinicians, nutritionists, and food technologists, who are committed to developing probiotics or probiotic-based foods or supplements for consumers. And we already know some of the excellent properties of probiotics, such as anti-pathogenic, anti-inflammatory, anti-cancer, anti-allergic, and anti-obesity activities, and their effects on the brain and central nervous system.

Connie: Can we first talk about the antibacterial activity of probiotics?

Dr. Hofstadter: Sure. One of the most researched effects of probiotics is to regulate the intestinal microbiota against pathogenic microorganisms. Probiotics produce various metabolites, such as short-chain fatty acids like Lactic acid, acetic acid, formic acid, butyric acid and propionic acid. According to reports, these fatty acids can inhibit pathogens such as Salmonella, Salmonella typhimurium and Clostridium difficile.

Connie: Are there any other benefits of fatty acids for the intestines?

Dr. Hofstadter: It has been reported that single-chain fatty acids can maintain proper pH conditions in the colon. Not only that, single-chain fatty acids can significantly promote the metabolism of foreign compounds and carcinogen residues in the intestine.

Connie: In addition to short-chain fatty acids, what other substances can probiotics produce to inhibit pathogen infection?

Dr. Hofstadter: Probiotics can also produce various inhibitory compounds to reduce pathogens. These compounds include peptides, bacteriocins, organic acids, hydrogen peroxide, diacetyl and hydrogen peroxide.

Connie: What are the effects of metabolites produced by probiotics on cells?

Dr. Hofstadter: They can regulate the pathways of cell proliferation, differentiation, and apoptosis. Probiotics also promote the host’s immune regulation pathways against pathogens, such as the secretion of anti-inflammatory compounds.

Connie: So, what aspects are involved in the anti-inflammatory activity of probiotics?

Dr. Hofstadter: To answer this question, let me first give you some background on two diseases: Ulcerative colitis and Crohn’s disease, which are the most common chronic inflammatory diseases and are classified as inflammatory bowel diseases. They can cause digestive disorders and intestinal inflammation in patients with abdominal pain. The main pathogens that cause Crohn’s disease are Salmonella, Campylobacter jejuni, Clostridium difficile, and Adenovirus. So getting into the relation between these diseases and probiotics. In overcoming human cadmium-related problems, Streptococcus rhamnosus, Escherichia coli, and Streptococcus brucei have been reported as potential therapeutic probiotic strains. In contrast, ulcerative colitis mainly affects the lining of the colon and rectum. Supplementing various probiotics, such as Streptococcus brucei, Lactobacillus casei and Bifidobacterium, has been shown to regulate the balance of intestinal microbes. So, now you know, protiobics can be used as an alternative therapy for the treatment of inflammatory bowel disease.

Connie: What is the reason for their effect on inflammatory bowel disease?

Dr. Hofstadter: The intervention of probiotics on inflammatory bowel disease is believed to be due to the competition with symbiotic pathogenic bacteria and its impact on the overall immune response system.

Connie: Now moving on to our next topic. Can you tell us under what background was the anti-tumor activity of probiotics developed?

Dr. Hofstadter: We all know that proteomics, genomics, and molecular pathology have been used as technical tools to study the mechanism of cancer. This has increased public awareness of cancer. At the same time, new drugs or molecules with attractive anti-cancer properties have been discovered using biotechnology and nanotechnology. However, the tolerance to its load and side effects has been the main limitation of most drugs. In this context, probiotics with anti-cancer effects have attracted great interest in preparing effective anti-cancer targets with minimal or no side effects.

Connie: Is there a specific mechanism to describe the anti-tumor activity of probiotics?

Dr. Hofstadter: Many mechanisms of action have been proposed, but the specific one is still unclear.

Connie: I heard that probiotics play a vital role in maintaining the dynamic balance in the colon and maintaining sustainable physical and chemical conditions. Are there any examples to support this statement?

Dr. Hofstadter: Yes, some studies have reported that the pH drop caused by excessive bile acids in the stool may be a direct cytotoxic factor that affects the colonic epithelium and leads to the occurrence of colon cancer. Probiotics are a solution to this problem. Probiotics can maintain the balance of the intestinal environment, adjust pH and bile acid distribution, and bind and degrade potential carcinogens. Not only that, probiotics produce single-chain fatty acids that can act as signal molecules that affect the immune system, cell proliferation, and apoptosis.

Connie: Back to the anti-cancer effects of probiotics, any relevant clinical trials going on?

Dr. Hofstadter: There are many new reports on the anti-tumor activity of different probiotic strains. So far, in vitro studies have shown that probiotics can play an important role in neutralizing cancer. However, these have not been supported by in vivo data. So we still need to verify their anti-tumor effect in in vivo models and progress in animal and clinical trials.

Connie: Let’s hope that we will soon see in vivo studies to back the in vitro studies on probiotics’ anti-tumor effects. Next, let’s discuss the anti-allergic activity of probiotics.

Dr. Hofstadter: In recent years, allergic reactions caused by different food ingredients and by immune disorders have been on the rise globally. It creates a serious economic and social burden. The indispensable molecular mechanisms of the etiology of allergic diseases, as well as new treatment strategies, are essential to prevent allergic reactions to food ingredients. In this context, the role of microflora in allergies is now widely studied. However, the role of probiotics as a treatment has not been noticed until recently.

Connie: Have the probiotics passed the anti-allergic test? What is their anti-allergic mechanism of reaction?

Dr. Hofstadter: So more people have realized the beneficial effects of probiotics and their role in the prevention of allergic diseases. Different strains have been tested for anti-allergic reactions. The tested probiotics showed a common mechanism for anti-allergic reactions. They can regulate innate lymphoid cells through Toll-like receptors and produce butyric acid as one of the single-chain fatty acids that protect intestinal inflammation. Probiotics can also increase foxp3 protein acetylation and immunomodulatory activities, such as increasing the secretion of interleukin-4 and interferon-γ.

Connie: We all know that accumulating fat in the body can directly damage health. How do probiotics play a role in fighting obesity?

Dr. Hofstadter: Right, so the fat accumulation has to be with increased energy supply and sedentary lifestyle, resulting in an imbalance in energy intake and consumption. And probiotics have physiological properties dedicated to regulating the health of microorganisms in the host environment. Many studies have shown that by activating the sympathetic nervous system, lipolysis and thermogenesis can reduce weight loss. Probiotics play an important role in stimulating sympathetic nerves.

Connie: Can you tell us the anti-obesity mechanisms of probiotics?

Dr. Hofstadter: The obesity mechanism of probiotics includes maintaining intestinal homeostasis, enhancing intestinal epithelial barrier function, producing conjugated linoleic acid and other health-promoting substances, competitively adhering to the intestinal mucosa, regulating the immune system by releasing anti-inflammatory compounds, and adjusting energy dynamic balance.

Connie: Probiotics also have certain effects on the brain and central nervous system. Does this mean that probiotics are related to certain neurological diseases?

Dr. Hofstadter: You can say so. In fact, the composition of the intestinal microflora is related to both neurological and gastrointestinal diseases. In addition, people are always working to advance promising therapies for the treatment of central nervous system diseases with probiotics.

Connie: So with so much research going on around probiotics, do you think there is any hope for them to become a new strategy for the treatment of neurological diseases?

Dr. Hofstadter: There are only a few studies on probiotics in humans, but the existing data on the use of probiotics to treat neurological diseases are promising. For example, a study conducted in 2005 indicated that probiotic culture may be used as adjuvant therapy for the treatment of major depressive disorders, for which stress is an important factor. Stress is thought to change the composition of the gut microflora, leading to a decrease in lactobacilli and bifidobacteria.

Connie: So, it is conceivable that the intestinal microflora is of great significance in chronic stress. Can you list some specific strains that are related to the treatment of depression?

Dr. Hofstadter: Bifidobacterium infantis exhibits antidepressant properties by normalizing cytokine and tryptophan levels, and elevated cytokine and tryptophan levels are associated with depression. In addition, probiotics such as rhamnose and Lactobacillus plantarum are known to have anxiolytic and antidepressant effects on mice. These are some early examples of mental microbes. In animal experiments, psychobiological agents have been shown to regulate the levels of neurotransmitters, serotonin, dopamine and their metabolites. So psychobiological agents have great potential for treating neurological diseases.

Connie: You may notice that there are already a variety of probiotic-related drugs that appeared on the market for different diseases. What can you tell us about these drugs?

Dr. Hofstadter: Traditionally, adding probiotic cultures to fermented foods has a limited shelf life and cold storage time. In order to solve this problem, freeze-dried probiotics can also be bought on the market in the form of capsules, powders, sachets, and tablets at health stores, with a longer shelf life. Among the probiotic products available on the market, chewable tablets and mixing probiotic powder with other active ingredients are also a trend. Medical professionals have recommended probiotic preparations for the treatment of various gastrointestinal diseases.

Connie: Although we know that probiotic strains or their components can be promising drugs for the treatment and prevention of many diseases in the near future, there are still many aspects that need to be further improved. What should researchers do next?

Dr. Hofstadter: Certainly. The reported diversity of probiotic strains and their further application in therapy requires a comprehensive understanding of the organization at the genomic level. Once the genome organization is elucidated, further applications of synthetic biology and genome editing tools will make it easier to design probiotics with enhanced activity as therapeutics.

Connie: It was a great discussion. That would be all for today. Thank you, Dr. Hofstadter for bringing us this interesting topic. Thanks everyone for listening. We will see you next Saturday evening.

Dr. Hofstadter: Thanks everyone. I hope I will see you next time.