Connie: Good evening, dear friends. It’s great to have you here with us. Thank you for joining us again on this beautiful Saturday evening. Today, we invite Dr. Hofstadter to our program. Thank you for being here, Dr. Hofstadter.
Dr. Hofstadter: Thanks for having me. Hello everyone. Excited to be here.
Connie: The human body’s immune system is very powerful and complex. It must always be vigilant and be able to distinguish between enemies and friends. Unfortunately, it does not always function normally, and sometimes even attacks its own cells, resulting in a variety of autoimmune diseases, including multiple sclerosis and rheumatoid arthritis. At present, researchers do not know exactly what causes the immune system to go wrong. To find the answer, more and more studies have begun to focus on the trillions of microorganisms living in the body. They are called the body’s microbiome. Today, we are going to discuss the role of gut microbes in allergy and autoimmune diseases. Where would you like to start, Dr. Hofstadter?
Dr. Hofstadter: Let’s start from the most basics. It is estimated that nearly 20 percent of the world’s population suffers from some form of allergic disease. The mechanism of allergy relies on the activity of different subtypes of T cells. The person experiencing allergy has a dominance of T helper 2 cell-mediated immune response. The type of immune response is controlled by regulatory T cells whose activity is crucial for immune tolerance and hyperreactivity. Activation of T helper 2 cells by regulatory T cells results in the production of interleukin 4, 5, 13 and induction of inflammation by recruiting eosinophils and allergen-specific immunoglobulin E class switching in B cells. And it’s already known that atopic or allergic disorders develop under the influence of a variety of heterogeneous factors including genetic predisposition, environmental factors, tempering innate and acquired immune responses, et cetera.
Connie: That’s much more clear. Probiotic-induced protection against allergic diseases including atopic dermatitis, food allergies, and airway allergy has been established in several animal studies and human clinical trials. In addition, the consumption of probiotics can lead to immune tolerance by activating the maturation of T helper 1 cells and inhibiting T helper 2 cell response. So can you give us some specific examples?
Dr. Hofstadter: Sure. The relation between the composition of gut microflora and allergy has also been established by many researchers. Some have proposed that modification of gut colonization with the help of supplemented probiotic strains during pregnancy and early infancy could down-regulate the onset of allergic diseases. I think it was only recently that a meta-analysis explored the effect of Lactobacillus rhamnosus and Bifidobacterium animalis subspecies lactis on the development of allergic diseases and sensitization in late infancy and early childhood. Like they expected, they observed that probiotics could effectively reduce the incidence of eczema in probiotic-consuming subjects.
Connie: That’s exciting. Did they figure out the mechanism of probiotics’ effect on allergic diseases?
Dr. Hofstadter: The mechanism was explored by another group of researchers using pre and postnatal consumption of Lactobacillus reuteri. So basically, supplementation of L. reuteri can improve immunoregulatory capacity by decreasing Toll-like receptor 2 induced response during infancy. Many other studies using mice have found direct effects of probiotics on airway allergy, including decreasing eosinophil counts in bronchoalveolar lavage and interleukin 5 and interleukin 13 levels in lungs and directly inducing mucosal cluster of differentiation 103 positive dendritic cells and differentiation of regulatory T cells.
Connie: Rheumatoid arthritis is a chronic, systemic disease with inflammatory synovitis with unknown etiology. It is characterized by multiple joints, symmetry, and aggressive joint inflammation of the hand and foot facet joints, often accompanied by involvement of extra-articular organs and positive serum rheumatoid factor, which can lead to joint deformities and loss of function. Does probiotic also play an important role in rheumatoid arthritis?
Dr. Hofstadter: Yes. Probiotics can prevent the pathology of autoimmune diseases. For example, probiotics could alleviate the symptoms of rheumatoid arthritis. The disease developed by the presence of autoantibodies called rheumatoid factor and anticitrullinated protein antibodies can cause inflammatory response at small joints such as hands, wrists, feet, and progression of bone and joint damage. The direct connection of the composition of the gut and oral microbiota with the pathogenesis of rheumatoid arthritis has been detected by many groups. But unfortunately, the specific contribution of commensal microflora could not be recognized to date.
Connie: But have the specific mechanisms of probiotics’ beneficial effect on rheumatoid arthritis been recognized?
Dr. Hofstadter: Yeah. To put it simply, probiotics are reported to significantly modulate the markers in arthritis animal models. The modulation of cytokines involves lowering of pro-inflammatory cytokines, such as interleukin 1, interleukin 6, macrophage chemoattractant protein 1 and tumor necrosis factor α, and upregulation of the level of anti-inflammatory cytokines, like interleukin 4, interleukin 10.
Connie: But these were observed in animal models. Any results from clinical trials?
Dr. Hofstadter: Of course. Clinical benefits of probiotic supplements have also been reported in human subjects. Similarly, there is research demonstrating that probiotics affected the level of inflammatory markers. Some markers I can think of are erythrocyte sedimentation rate, tumor necrosis factor α, interleukin 1β, interleukin 6, interleukin 10, and interleukin 12 as well as oxidative stress markers. This explains that the efficacy of probiotic treatment largely relies upon several host-associated factors and varies from individual to individual.
Connie: That makes sense. Well, do you think the host factors can affect the probiotic intervention outcome?
Dr. Hofstadter: Absolutely. One article has explained that many factors like genetic build-up, age, sex, and microbiological composition can significantly influence the mechanism of the immune system and how probiotics affect them. And this could answer the question as to why we see conflicting results of probiotic interventions on allergic disease. In general, it can be deciphered from the involvement of mentioned above variable factors which largely affect the results of clinical studies.
Connie: Host genetics, age, resident microbiota, I can understand these factors to some extent. But how does gender play a part in this?
Dr. Hofstadter: Yeh I know what you mean. But yes, there are differences in immune system functioning in different genders. And many studies have verified that more allergic airway inflammation and airway hyperresponsiveness are developed in females. Besides, there is ovarian hormone fluctuation during the menstrual cycle and pregnancy effects. They all can affect probiotic intervention outcomes.
Connie: Okay. Now I understand. According to our discussion today and an overview of currently present data, we can conclude that probiotics can help alleviate allergy and autoimmune diseases by balancing between native microbiota, regulating inflammatory mediators, and developing the immune system.
Dr. Hofstadter: That’s right. However, high levels of variability in related studies in the context of different formulations of probiotics for different types of patient populations and their respective outcomes have prevented the observation of any significant effect of probiotics on allergic diseases. In other words, there is still a long way to go.
Connie: Exactly. Ok, that’s it from us today. I hope you enjoyed today’s episode. Thanks, Dr. Hofstadter, for sharing your insight with us. And thanks, everyone, for listening. We will continue our discussion on probiotics next week. See you then!
Dr. Hofstadter: Thanks, everyone. I hope we will see you next time.