Probiotics are particularly beneficial living microorganisms that help improve human health. Although probiotics have long been used as nutritional supplements in various cultures around the world, new research has investigated their antimicrobial and immune boosting effects in individuals. Lactobacillus and Bifidobacterium are popular probiotics used worldwide that benefit human health by acting as antibacterial, antiviral, and antifungal agents, reducing pathogen binding to the host receptor and thus capturing pathogenic microorganisms. Probiotics have been shown to be beneficial in a variety of bacterial and viral diseases worldwide. The regulation of the host’s immune response is one of the most important mechanisms of probiotic action. Immunomodulatory effects of probiotic-derived compounds have been characterized using genomic and proteomic analysis. These compounds have the ability to regulate and initiate mucosal immunity against various diseases. Probiotics produce many bactericidal compounds, which inhibit the growth of pathogenic microorganisms and their toxins, promoting the sustainability and structural integrity of enterocytes. This chapter focused on recent scientific research findings that help us better understand how probiotics regulate the host immune response and how they can be used to prevent and treat disease and there beneficial role to improve the health status of individuals.
The human body is prone to many virulent microbes and their oxidative metabolic substances. The human body is shielded from potentially pathogenic microbes by the immune system . The gastrointestinal tract, which is approximately 7.5 meters long, is the largest area of the immune system. Furthermore, trillions of bacteria reside in the gut, particularly in the colon, which served as the main reservoir for these mutualistic species. Most of the time, it is said that the number of human cells in the body is ten times less than that of bacterial cells, while this proportion has been revamped to about 1:1 . Normal vaginal and fecal microorganisms were injected at birth to study the host microbe’s relationship with the newborn. This inoculum contains aerobic, anaerobic, gram-positive, and gram-negative bacteria belonging to dominant species such as Sneathia spp., Lactobacillus spp., and Prevotella spp. . It has been studied that how gestational stage, environment, type of delivery, attitude, and breastfeeding habits influenced the proliferation and stability of the infant’s microbiome .
The host-microbe relationship is critical for the growth of the gastrointestinal immunity within the first weeks after giving birth. The proliferation and growth of gut microorganisms continues until about the age of two years, at which point the intestinal immune system is said to be mature . The intestinal environment of gut microorganisms is generally stable, particularly at the species and genus levels. Besides that, irrational antibiotic use, pathogenic parasites, malnutrition, or cold and hot stress all have an impact on the structural composition of gut microbiota .
Antimicrobial drugs, as well as human-targeted medicines, have been attributed to changes in gut microbial composition. More than a thousand antimicrobial drugs have been evaluated against forty different intestinal bacteria around the world. They discover 24 drugs that inhibit the growth of one or even more bacterial strains in vitro . The defensive mechanism is triggered by innate immunity when an individual’s body is exposed to a foreign particle or sustains tissue damage. Innate immunity protects cells physiology by signaling adaptive immune responses to persistent threats and stimulating inflammatory response. Inconsistent innate and adaptive responses, on the other hand, result in highly inflammatory reactions, tissue damage, and disease. The host mucosal immune response induced by gut microbiota is important for maintaining intestinal homeostasis and developing a systemic defense response. Manipulation of the intestinal microbiota can thus be a viable alternative route to improving health and to prevent and/or cure illness .
Probiotics were described as ‘live microorganisms that impart benefits to the host health when taken in sufficient quantities as component of food”. Saccharomyces, Lactobacillus, and Bifidobacterium are three important probiotic Genus that have been extensively researched and used in animal and human feed . Recent research indicates that probiotics have a number of beneficial effects on the host’s gastrointestinal tract protection mechanism. They produce bactericidal substances by which they counteract pathogenic microorganisms’ consequences and bind to the intestinal epithelium by interacting with pathogenic microorganisms and their toxins. Probiotics facilitate the longevity of epithelial cells, improve the immune barrier, and improve the immune response to intestinal epithelium, all of which lead to gastric mucosal homeostasis . Most notably, immune system regulation is among the most potential factors behind probiotics’ beneficial health effects. Probiotics strengthen innate and adaptive immunity and suppress bacterial infection through toll-like receptor-regulated signal transduction pathways. Probiotic bacteria have been seen to enhance intrinsic host immune mechanisms. The use of probiotic microbes has significant effects on people’s immune systems, such as stabilizing the non-immunological or innate immune response triggered by gut microbes, improving adaptive intestinal immune response, and regulating non-specific inflammatory and hypersensitivity reactions .
2. Historical background of probiotics
The concept of probiotics therapy emerged after the discovery of gut microbiome that is an inherent part of the intestinal epithelial cells. A probiotic is represented as a live microorganism’s dietary supplement that benefits the individual by boosting the intestinal microbiome in the gastrointestinal tract. The probiotic definition is incomplete for the aim of human health and nutrition. In response, the European Commission and the International Institute of Life Sciences collaborated to reframe the concept of probiotics as a live microbial food item which is beneficial to human health .
In 1953, German researcher Werner Kollath coined the term probiotic, which is comes from the Latin terms pro, which means for, and biotic, which means “bios” or “life.” Probiotics were defined by Lilly and Stillwell in 1965 as substances produced naturally by one microorganism that promotes the growth of another. In 1992, Fuller described probiotics as “live microorganisms added as a supplement in feed that benefits the host by improving its intestinal microbial balance” Probiotics have a modern history dating back to the early 1900s, when future Nobel laureate Elie Metchnikoff, a Russian scientist working at the Pasteur Institute in Paris, performed groundbreaking research .
Louis Pasteur established the microbes required for the fermentation process, while Metchnikoff first sought to determine the potential impact of the microbiota on public health. He attributed Bulgarian village peoples’ long life spans to their regular consumption of yoghurt, which are fermented dairy products. He related this to Stamen Grigorov, a physician who found the Bulgarian bacillus, and further proposed that lactobacilli could mitigate the decaying impact of digestive fermentation, that led to illness and aging. Furthermore, Socrates said over two thousand years ago that “death lies in the guts” and that “poor absorption is the root of all evil.” Metchnikoff also reported that toxins generated by microbial decomposition in the gastrointestinal tract and then discharged into to the bloodstream trigger aging . Such microbes were originally referred to as decomposing microbes, but they are now known as proteolytic clostridia. Metchnikoff also noted that “the gastrointestinal microbiota’ reliance on food allows us to take steps to change the microbiome in our gastrointestinal tract and exchange pathogenic microorganisms with good bacteria.” Metchnikoff scientific theory of probiotics was the foundation for the first dairy industry in France .
Modern techniques have selected probiotics strains that manufacture fortified milk with strong nutritional and organoleptic features more than anyone else. Yoghurt was the first functional fermented food based to historical evidence . However, since probiotics are usually associated to the consumption of fermented foods, they have a long and distinguished history. In ancient Indian Vedic literature, milk and milk products are associated to a reliable and comfortable life. According to legend, the first kefir grain was distributed by Prophet Muhammad (SAW) to the descendants of Caucasian mountaineers as a reward. Kefir is a fermented milk drink that contains a lot of lactic acid bacteria and probiotics. Cheese and yoghurt have been used by Hippocrates, Marco Polo, Galeno, and Chinese people throughout history .
3. Probiotics stimulate innate immune system
The most distinguished cells of natural immunity in probiotic research are the dendritic and epithelial cells. These are the first cells to interact with the gut microbiota and its toxic metabolites. Gut associated lymphoid tissue (GALT) and intestinal mucosa is the reservoir of intestinal dendritic cells. Dendritic cells are also known as detector cells because they have unique receptors that attach to specific sites on pathogen surfaces. Dendritic cells also act as a catalyst for various forms of signaling pathways that modify phenotypes and secreted cytokines such as Toll-like receptors and c-type lectin receptors .
The use of probiotic strain
The absorptive role of intestinal epithelium is well described. Epithelial cells produce a mucosal barrier to safeguard the individual from harmful microbes and toxicants. The intestinal mucosa barrier has a powerful connection with the intrinsic immune system of the Peyer’s patches and lamina propria . Probiotics are well-known for preserving the integrity of the intestinal barrier through a variety of mechanisms, including starvation of infectious agents as they compete for nutrients, detachment of bacteria from intestinal epithelium, which prevents pathogen invasion, immune response regulation, and aiding in regulatory T cell responses. Most of these are probiotics’ positive effects on the host’s internal health . The use of
Multiple probiotic strains of the genus Bifidobacterium, such as
4. Probiotics stimulate humoral immune system
Probiotics are used to sensitize the host’s immune system to potentially dangerous pathogens. Oral administration of B. bifidum increased humoral immune response to egg albumin, whereas
Probiotic derived proteases have been shown to digest cow milk casein and produce peptides that inhibit inflammatory cytokines in healthy people. A study was conducted to see whether caseins digested by probiotic bacteria producing proteases might induce the production of cytokine and anti-CD3 immunoglobulin mononuclear cells in atopic dermatitis in infants with cow milk allergies. Casein from cow’s milk stimulates the synthesis of IL-4, which causes hypersensitivity . Oral administration of
The ability of probiotics to increase the number of T-regulated lymphocytic cells contributes for their anti-inflammatory and anti-colitis properties.
Probiotics strain produced short chain fatty acids molecules such as propionate, isobutyrate, acetate, butyrate etc., which directly or indirectly regulate the homeostasis of T-cells. Butyrate activates Foxp3+ cells and Treg cell production outside of the hypothalamus. Propionate regulated the production of T-cell by inhibiting histone deacetylase. Probiotics e.g.
Probiotics have the ability to shift the immune response from Th2 to Th1. L. casei can stimulate IL-12 development, polarizing the Th1 response and mitigating Th2 linked illnesses.
Probiotics have a direct effect on the cells of the lamina propria and payers patches, resulting in an increase in IgA production cells. IgA plays an important function in the prevention of mucosal pathogens. Toxins are neutralized by IgA, which prevents pathogens bacteria from binding to intestinal epithelial cells.
5. Role of probiotics as antibacterial
The oral cavity is a highly complex structure containing over 700 different types of bacteria. When there is a disturbance in this environment, abnormalities such as periodontal disease may occur, resulting in a reduction of indigenous microbial populations to the advantage of infectious agents. The causative agents of oral cavity disease are
Anti-bacterial substances formed by probiotic strains included defensin, acetaldehydes, hydrogen peroxide, bacteriocins, organic acids, ethanol, and peptides. Peptides and bacteriocins, in general, are essential in increasing the vascular permeability of target cells that contributes to activation of the membrane permeability and, eventually, cell damage .
Probiotics have antibacterial effect, which is an essential feature. Bacteriocin synthesis may be one way to accomplish this antibacterial activity. Bacteriocins are produced by the industrial probiotic strains
The most commonly used probiotic strains are from the Lactobacillus genus, which is recognized as safe. Some researchers have explained the function of probiotics in the buccal mucosa during the last few decades. Intake of lactic acid bacteria containing items has been shown to mitigate dental caries of mutant streptococci, but the studied species were ATCC strains rather than standard probiotic species such as
6. Role of probiotics as antiviral
A number of microorganisms have been found in the human respiratory tract as the primary source of the respiratory virus. We may reduce the occurrence of disease development in humans by limiting the penetration of respiratory tract viruses into the membranes of mucosal epithelial cells. The human body contains a diverse community of mutually advantageous commensal bacteria known as microbiota . Probiotics are microorganisms that have potential health benefits when eaten in a specific amount. There are two basic types of probiotics: Lactobacillus and Bifidobacterium and Both have a positive impact on human health since it acts as an antiviral agent, lowering the binding ability of viruses to the host receptor and thereby capturing the virus. Probiotics administering protects individuals from various respiratory viral infections like Respiratory syncytial virus, SARS-CoV-2, Influenza A virus. This antiviral activity was investigated by the strain’s specificity as well as the host immune status .
The COVID-19 disease affects the lungs and the gastrointestinal tract, inducing pro-inflammatory Th1-cells to release various cytokines such as TNF-alpha leading to the establishment of the cytokine storm. Dysregulation in the intestinal microbiome contributes to an imbalance of Th1 and Th2, which stimulates the formation of pro-inflammatory cytokines and, eventually, a cytokine storm in epithelial cells in the lungs . Probiotics promote the proliferation of “beneficial bacteria” in the intestine, resulting in a change in the stability of Th1/Th2 cells, which lowers the cytokine storm and the severity of infections. It was recently found that using probiotic bacteria derived from Lactobacillus and Bifidobacterium improves the chance of healing from COVID-19 patients.
7. Role of probiotics as antifungal
The global fungal load is extremely high, and it is expected to rise even higher as the proportion of immunocompromised people rises. In contrast, the drugs used to treat fungal pollutions are extremely small, and some of them are extremely dangerous.
Aflatoxin is an extremely hepatotoxic bioactive compound produced by fungi, which is a major global concern. A toxin-free feed is demanded by the existing agriculture and livestock production industries. Use of such microbes to food preservation has grown in popularity in recent years, owing to customer needs for less reliance on chemical preservatives. Lactic acid bacteria are widely regarded as a “beneficial organism,” that is used to avoid contamination of food and feed, as well as to chemically store food. It is also intended to produce antimicrobial agents .
Probiotics have been shown to decrease
Nowadays, the discovery of the use of probiotic strains has improved our understanding of the relationship between diet and people’s health. Probiotics boost innate and humoral immunity against pathogens. Probiotic bacteria bind to gut epithelial cells and release cytokines (IFN-γ) and interleukins (IL-10) that establish a microclimate in the tracheae, bronchi, and reproductive organs and gut lamina propria, triggering clonal proliferation of B cells to make IgA and activating Treg cells, thereby maintaining immune balance in the gastrointestinal tract. COVID-19 is a newly emerging virus that causes deadly disease all over the world. Probiotic strains, especially lactobacillus species therapy, may be critical in controlling COVID-19, and probiotic treatment may be considered as a choice for the reduction and mitigation of COVID-19 infection globally.
Conflict of interest
The authors declare no conflict of interest.
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