**2. Probiotics and immune health**

Hippocrates (460-370 EC) stated, "All diseases begin in the gut." Both microbial diversity and abundance in the gut play an important role in maintaining human health. The attachment, growth, and penetration of pathogenic microorganisms on the gut surface can essentially be prevented by microbiota. Pathogen resistance, both by direct interaction with pathogenic bacteria and by influencing the immune system, is influenced greatly by the intestinal microbiota [9, 10]. Many diseases start with an initial imbalance of human resident microflora and the related immunobiological reactivity [11]. One key player in immune health is the gut, a part of the body that is constantly exposed to toxins and foreign antigens, such as those from food and microbes. According to nutrition and immune expert Meydani, "The gut is the largest immune organ in the body, accounting for 25% of the immune cells in the body that provide 50% of the body's immune response." Meydani called intestinal flora "forgotten organ" because of their vital but still underestimated health functions [12]. There are more than 400 species of bacteria residing in the gut, and they have symbiotic relationships with the body. There are 100 trillion bacteria in our intestines. They form an ecosystem like a "flower garden", reported Haruji Sawada, director of the Yakult Central Institute, at the Yakult International Nutrition and Health Conference on May 17, 2010, in Tokyo. The mammalian gut immune system should be viewed as a complex interplay between physical, chemical, and cellular barriers, a vast community of bacteria, and a plethora of host immune cells which mediate innate and adaptive immunity. The intestinal microbiota helps in proper development of the host immune system, which in turn regulates the homeostasis of the microbiota [13]. Accu‐ mulating evidence over the last decade indicates that the immune system and microbiota interaction should be finely balanced and any perturbations of this interaction would result in microbiota and immune dysbiosis, leading to inflammatory disorders The rapid surge in the emerging new-age disorders such as inflammatory bowel disease (IBD), rheumatoid arthritis, cardiovascular disease, and metabolic syndrome has driven investigators to explore their etiology in multiple directions such as genetics, diet, and environmental factors, as well as immune system/microbiota interactions. In addition, the practice of strict hygienic and sanitary conditions and consumption of highly processed foods containing high fat, high carbohydrate, and low fiber with numerous food additives and preservatives may account for altered microbial composition, metabolism, and interaction with host immunity. Nearly all the above diseases are characterized by local as well as systemic low-grade chronic or subclinical inflammation in which the inflammation originated in the intestine via the interaction between host immune system and microbiota.

mechanisms including innate and adaptive immune responses. The immunological mecha‐ nisms supporting probiotics and prebiotics effects continue to be better defined with novel mechanisms being described for dendritic cells, epithelial cells, T regulatory cells, effector

Looking to probiotics to support immune health is nothing new; the idea has existed for more than 100 years [2]. For millennia, humans have consumed microorganisms via fermented foods. Human beings and gut microbiota are in a symbiotic relationship, and the hypothesis of a "super organism" composed of the human organism and microbes has been recently proposed. The gut microbiota performs important metabolic and immunological tasks, and the impairment of its composition might alter homeostasis and lead to the development of

The most common illnesses associated with alterations of the gut microbiota include inflam‐ matory bowel disease, gastrointestinal infections, irritable bowel syndrome and other gastro‐ intestinal functional diseases, colorectal cancer, metabolic syndrome and obesity, liver

Neural pathways and central nervous system (CNS) signalling systems, according to new studies, can be activated by bacteria in the gastrointestinal (GI) tract, including commensal, probiotic, and pathogenic bacteria. Novel approaches for prevention and treatment of mental illness, including anxiety and depression [6], may be provided by actual and future animal and clinical studies, aimed at understanding the microbiota–gut–brain axis. In theory, every disease associated with the impairment of intestinal microflora might benefit from the

The purpose of this review is to address the most recent findings regarding probiotic regulation of immune health. Probiotic genes and probiotic-derived factors involved in the regulation of host immunity, molecular targets of probiotic action responsible for the host immune respons‐ es, and roles and mechanisms of probiotics in prevention and treatment of diseases [7], which

The role of specific microorganisms and the overall diversity of the microbiota in many human diseases can be understood to a great extent owing to the rapid growth of metagenomics strategies. Therapies focused on specific effects of different probiotics and prebiotics on the

Hippocrates (460-370 EC) stated, "All diseases begin in the gut." Both microbial diversity and abundance in the gut play an important role in maintaining human health. The attachment, growth, and penetration of pathogenic microorganisms on the gut surface can essentially be prevented by microbiota. Pathogen resistance, both by direct interaction with pathogenic bacteria and by influencing the immune system, is influenced greatly by the intestinal microbiota [9, 10]. Many diseases start with an initial imbalance of human resident microflora

are included in clinical applications and mechanisms of action, are of special interest.

gut microbiota [8] can be helped by the development of this knowledge.

lymphocytes, natural killer T cells, and B cells [1].

disorders, allergy, and neurological diseases [4,5].

therapeutic modulation of the gut microbiota.

**2. Probiotics and immune health**

microbiota-related diseases [3].

198 Immunopathology and Immunomodulation

Several beneficial effects of probiotics on the host intestinal mucosal defense system, including blocking pathogenic bacterial effects by producing bactericidal substances and competing with pathogens and toxins for adherence to the intestinal epithelium, have been identified. Probi‐ otics promote intestinal epithelial cell survival, enhance barrier function, and stimulate protective responses from intestinal epithelial cells [14-16] in the case of intestinal epithelial homeostasis. What matters most is that the modulation of the immune system is one of the most reasonable mechanisms underlying the beneficial effects of probiotics on human health. Enhancement of the innate and adaptive immunity and modulation of pathogen-induced inflammation are the discovered effects of probiotics.

Strictly defined strains using genetic, serological, microbiological, and biochemical analyses; lack of pathogenicity, lack of cancerogenicity, presence of beneficial factors; possibility for colonization of the large intestine; viable cultures; acid and bile resistance; proved clinical efficacy are among the requirements for the organisms to be used as probiotics [17].

The established probiotics that meet these criteria are generally lactic acid bacteria (LAB), most commonly *Lactobacillus* and *Bifidobacterium* species, but also *Lactococcus, Streptococcus,* and *Enterococcus* species and certain yeast strains. Numerous other LAB have shown probiotic potential in animal studies. For the treatment of IBD, several probiotics have been shown to be efficacious: *Lactobacillus casei, Lactobacillus plantarum, Lactobacillus bulgaricus,* and *Lactoba‐ cillus acidophilus*; three strains of *Bifidobacteria* and *S. thermophilus*. In recent years, evidence has accumulated that probiotic strains can exhibit the same activities as commensal bacteria, including immunomodulation [5,11].

Lactic acid bacteria are present in many feeds such as yogurt and are frequently used as probiotics to improve some biological functions of the host. Beneficial effects of the lactobacilli on the body have been identified in the treatment or prevention of acute viral gastroenteritis, after antibiotic-associated diarrhea, certain pediatric allergic diseases, necrotizing enterocoli‐ tis, and inflammatory bowel disease such as Crohn's disease and postoperative hernias. Probiotics have been long reported to aid in the treatment of many dysfunctions of the GI tract, and the mechanisms by which probiotics work have recently been elucidated. There are experimental and clinical data [18-24]. Probiotics are described as useful also in combating oxidative stress, improvement in mucosal immunity [25], and general immunity [26]. The desirable changes of the intestinal microbiota were achieved as yogurt was able to attenuate the symptoms of acute inflammation by reducing inflammatory cytokines and increasing regulatory cytokine IL-10-producing cells. The use of murine models demonstrated that the consumption of fermented milks can modulate the immune system and can maintain it in a state of surveillance, which could affront different pathologies such as cancer and intestinal inflammation on its part.
