Probiotics, Functional and Baby Foods

Recent studies are providing new insight into the mechanisms by which the microbiota regulates the colonization and eradication of pathogens. Particularly revealing the ability of commensals to restrain pathogen growth by dictating the metabolic pathways that control the competition for limited nutrients in the intestine. Furthermore, inflammatory responses have profound effects on the growth of pathogens and certain commensal species. However, the relative contributions of each metabolic pathway and the commensal species involved remain poorly understood. In addition, little is known about how the inflammatory responses affect interactions between pathogens and commensals. There is a delicate balance in microbiota populations in the gut and disruption in this balance leads to dysbiosis and overgrowth of pathobionts leading to pathologic immune responses and disease. The identification and characterization of natural “competitors” that suppress the growth of pathogens and pathobionts may lead to the development of rational approaches to manage intestinal disease. There is also a clear role for host immunity in controlling microbiota populations. However, recent studies have challenged a critical role of innate recognition receptors in determining the composition of the gut microbiota. Further studies are needed to clarify the mechanism by which the host regulates the microbiota.
 

Probiotics live microorganisms when administered in adequate amounts confer a health benefit on the host that have been studied for both human and animal applications, and worldwide research on this topic has accelerated in recent years. Administration of probiotics could be effective in the treatment of acute infectious diarrhoea in children and the prevention of antibiotic associated diarrhoea and nosocomial/community acquired diarrhoea. Encouraging evidence is also emerging for the effectiveness of probiotics in the prevention and management of pouchitis and paediatric atopic diseases, and the prevention of postoperative infections. There is also strong evidence that certain probiotic strains are able to enhance immune function, especially in subjects with less than adequate immune function such as the elderly. Efficacy of probiotics has been shown in the prevention of prevention of antibiotic-associated diarrhoea, sepsis associated with severe acute pancreatitis, improvement of lactose metabolism and cancers, the management of weight and lowering of blood cholesterol, but there is insufficient evidence to recommend them for use in other clinical conditions.

Gastroenterologists once defined gastrointestinal health as the absence of chronic disorder such as inflammatory bowel disease (IBD). However, this is too restrictive. The increasing frequency of digestive functional disorders, including non-ulcer dyspepsia and irritable bowel syndrome (IBS), justifies an enlargement of a definition that includes intestinal well-being and the overall impact on quality of life including reduction of disease risk. Some animal studies are required to investigate this concept. The intestinal microflora has been linked with a number of intestinal diseases including colon cancer, (IBS) and IBD however few details of their involvement have been elucidated. Since colon cancer and IBD can lead to extreme therapeutic approaches, including surgical excision, clarification of the role of the microflora in these diseases may significantly reduce morbidity. 

Presenting global evidence for their utility in children, Prof. Sherman illustrated that evidence through randomized controlled trails have demonstrated that certain probiotic strains are more effective than placebo in a variety of conditions affecting the gastrointestinal tract. Multiple meta-analyses indicate effectiveness in reducing the duration of acute enteritis in pre-schoolers and in reducing the frequency of necrotizing enterocolitis in pre-term babies. As probiotics exist naturally in some foods and are also available as dietary supplements in powder, capsule, and tablet forms. In 2002, the industry secured FDA designation of specific strains of B. lactis and Streptococcus thermophilus as substances generally recognized as safe (GRAS) in milk-based formulas for infants aged 4 months and older. Most probiotic bacteria are similar to the beneficial bacteria that occur naturally in the gut, including those of the Lactobacillus species (eg, L. acidophilus). Infants acquire other bacteria during their first months, mainly those of the Bifidobacterium and Enterobacter species. Bifidobacterium species dominate in the gut of breast-fed infants, whereas Enterobacter microbes dominate in bottle-fed infants. This difference in species, which has been identified as key to breast-fed infants’ superior immunity to many infections, has spurred much of the medical and pediatric communities’ interest in probiotics. Infant formula manufacturers have also taken interest

The use of probiotics for farm animals has increased considerably over the last 15 years. Probiotics are defined as live microorganisms which can confer a health benefit for the host when administered in appropriate and regular quantities. Once ingested, the probiotic microorganisms can modulate the balance and activities of the gastrointestinal microbiota, whose role is fundamental to gut homeostasis. It has been demonstrated that numerous factors, such as dietary and management constraints, can strongly affect the structure and activities of the gut microbial communities, leading to impaired health and performance in livestock animals. Probiotic microorganisms, which benefit from a ‘natural image’, can expect a promising future in animal nutrition. Controlled research studies demonstrate that they can positively balance gastrointestinal microbiota, and thereby improve animal production and health. However, care must be taken in the way that the probiotic candidate-strains are selected. Better knowledge of the structure and activities of the gut microbiota, functional interactions between gut microbes and interrelationships between microbes and host cells represent a fundamental aspect of future probiotic research. In this context new ‘omic’ technologies will be very helpful to better characterize and understand the effects of probiotics on the balance of the gastrointestinal microbiota. It will be possible to select more powerful or targeted strains on a scientific basis and follow their behaviour in the host animal. Thanks to these techniques, which are complimentary to anaerobic culture methods and gnotobiotic animal or cellular models, probiotic research has had, and will also certainly have in the future, a very important place in the improvement of animal health and nutrition.

The increasing interest in the preservation of the environment and the health of consumers is changing production methods and food consumption habits. Consumers increasingly demand safe functional foods that have beneficial properties for health mainly focused on the protection against carcinogenesis and oxidative processes. The consumption of fresh fruits and vegetables containing bioactive compounds has increased considerably in recent years and many studies have been carried out on the potential benefits of such compounds in different aspects of human health. At the same time, there has been a strong increase in studies addressing the benefits of biofertilization for plants and the environment. In this sense plant promoting rhizobacteria (PGPR) able to colonize the inside of plants tissues are especially interesting. These beneficial microorganisms are plant probiotics and promote the plant growth through different direct mechanisms such as nitrogen fixation, phosphate solubilization, and the production of different compounds such as phytohormones or indirect mechanisms such as the production of siderophores. To achieve both aims, the promotion of plant growth and the benefits for human health, it is necessary to use non-pathogenic microorganisms in biofertilization schemes.

Aquaculture is the world's fastest growing food production sector. However, fish culture is currently suffering from serious losses due to infectious diseases. The use of antimicrobial drugs, pesticides and disinfectant in aquaculture disease prevention and growth promotion has led to the evolution of resistant strains of bacteria. Thus, the research into the use of probiotics for aquaculture is increasing with the demand for environment – friendly sustainable aquaculture. The benefits of such supplements include improved feed value, enzymatic contribution to digestion, inhibition of pathogenic microorganisms, anti-mutagenic and anti-carcinogenic activity, and increased immune response. These probiotics are harmless bacteria that help the well-being of the host animal and contribute, directly or indirectly to protect the host animal against harmful bacterial pathogens. The use of probiotics in aquaculture has just begun, due to the fact that gastrointestinal microbiota of aquatic organisms has been poorly characterized, and their effects are not studied extensively.

Probiotic-derived factors have been described as capable of exerting probiotic activities through various mechanisms. However, it is important to distinguish between the concept of probiotic, which is necessarily based on the ingestion of live microorganisms, and the concept of microorganism-derived bioactive compounds that may have useful applications in nutrition and medicine. Bioactive compounds of bacterial or yeast origin, (antibiotics, for example), have been utilized in medicine for decades. Although there are many bacteria-derived products capable of inducing a health benefit, the concept of probiotic is only attributed to microorganisms administered as viable forms, providing the opportunity for a symbiotic relationship between the host, and resident, or in-transit, microorganisms. Secreted probiotic factors, such as reuterin from Lactobacillus reuteri, have been reported to inhibit adhesion and viability of known enteric pathogens, suggesting that probiotic supernatants could be a rich source of new antipathogenic compounds. In an in vitro study in human gastric epithelial cells, spent culture supernatants from certain lactic acid producing bacteria inhibited the growth and attachment of Helicobacter pylori. Roselli et al. demonstrated that supernatants of Bifidobacterium animalis MB5 and Lactobacillus GG could inhibit adhesion of E. coli K88 to Caco-2 cells, with the supernatant exerting identical beneficial effects following protease digestion, suggesting that proteins were not the active constituent.
 

Since probiotic-containing products in general do not require Food and Drug Administration  approval, they are commonly available in the market in various food formats such as fermented milk, cheese, yogurt and juice. In recent years, probiotics have been extensively studied as a treatment option of various diseases such as obesity, diabetes, cancer, human immunodeficiency virus infection, irritable bowel syndrome. Due to probiotic’s vulnerability to several environmental factors such as temperature and pH, maintaining the viability of probiotics has long been a hurdle to develop successful probiotic delivery systems. Hence to overcome these hurdles in probiotic delivery methods like encapsulation of materials and recent probiotic delivery technologies are being commonly used. Microencapsulation technologies have been developed to protect the bacteria from damage caused by external environment. By the introduction of a straw delivery system containing a dry form of the probiotic bacterium beverage manufacturers can now provide it to the consumer. In addition, viable spores of a spore forming probiotic are available in the market offering advantages during processing. In the same time, the potential of antibiotics’ substances with antimicrobial properties production by bifidobacteria is being explored in order to be applied in the food area.  
 

There is an increasing scientific and commercial interest in the use of beneficial microorganisms, or "probiotics," for the prevention and treatment of disease. The microorganisms most frequently used as probiotic agents are lactic-acid bacteria such as Lactobacillus rhamnosus GG (LGG), which has been extensively studied in recent literature. Multiple mechanisms of action have been postulated, including lactose digestion, production of antimicrobial agents, competition for space or nutrients, and immunomodulation. Studies of pediatric diarrhoea show substantial evidence of clinical benefits from probiotic therapy in patients with viral gastroenteritis, and data on LGG treatment for Clostridium difficile diarrhoea appear promising. However, data to support use of probiotics for prevention of traveler's diarrhoea are more limited. New research suggests potential applications in vaccine development and prevention of sexually transmitted diseases. Further studies are needed to take full advantage of this traditional medical approach and to apply it to the infectious diseases of the new millennium.

 

Overwhelming evidence from epidemiological, in vivo, in vitro, and clinical trial data indicates that a plant-based diet can reduce the risk of chronic disease, particularly cancer. In 1992, a review of 200 epidemiological studies showed that cancer risk in people consuming diets high in fruits and vegetables was only one-half that in those consuming few of these foods. It is now clear that there are components in a plant-based diet other than traditional nutrients that can reduce cancer risk. Functional foods containing physiologically-active components, either from plant or animal sources, may enhance health. It should be stressed, however, that functional foods are not a magic bullet or universal panacea for poor health habits. There are no “good” or “bad” foods, but there are good or bad diets. The range of food products containing probiotic strains is wide and still growing. The main products existing in the market are dairy-based ones including fermented milks, cheese, ice cream, buttermilk, milk powder, and yogurts, the latter accounting for the largest share of sales. The functional food market is expanding, especially in Japan its birthplace with further growth prospects in Europe and the United States and in most countries the largest share of its products is held by probiotics. Common foods containing probiotics include fermented and unfermented milk, miso, tempeh, and some juices, smoothies, nutrition bars, and soy drinks. The most common strains found in yogurt are L. bulgaricus and S. thermophilus.
 

Prebiotics are non-digestible, fermentable carbohydrates and fibers, such as inulin-type frucans and galacto-oligosaccharides, which exhibit health promoting properties to host through selective stimulation of growth and/or activities of a limited number of bacteria (i.e., probiotics).  Human milk contains substantial quantities of prebiotics. There is a paucity of Random Clinical Trials examining prebiotics in children, showing that there may be some long-term benefit of prebiotics for the prevention of atopic eczema and common infections in healthy infants for which confirmatory well-designed clinical research studies are necessary.
 

Depending on intended use of a probiotic (drug vs. dietary supplement), regulatory requirements differ greatly. If a probiotic is intended for use as a drug, then it must undergo the regulatory process as a drug, which is similar to that of any new therapeutic agent. Despite the promising evidence, the role of probiotics in human health as well as the safety of their application should be further investigated as the current knowledge of the characteristics that are necessary for their functionality in the gut is not complete. The factors that must be addressed in evaluating the effectiveness of the incorporation of the probiotic strains into such products are, besides safety, the compatibility of the product with the microorganism and the maintenance of its viability through food processing, packaging, and storage conditions. The product’s pH for instance is a significant factor determining the incorporated probiotic’s survival and growth, and this is one of the reasons why soft cheeses seem to have a number of advantages over yoghurt as delivery systems for viable probiotics to the gastrointestinal tract. Current technological innovations provide ways to overcome probiotic stability and viability issues offering new options for their incorporation in new media and subsequent satisfaction of the increasing consumer demand. The safety profile of a potential probiotic strain is of critical importance in the selection process. This testing should include the determination of strain resistance to a wide variety of common classes of antibiotics such as tetracyclines, quinolones and macrolides and subsequent confirmation of non-transmission of drug resistance genes or virulence plasmids. Evaluation should also take the end-product formulation into consideration because this can induce adverse effects in some subjects or negate the positive effects altogether. A better understanding of the potential mechanisms whereby probiotic organisms might cause adverse effects will help to develop effective assays that predict which strains might not be suitable for use in probiotic products.
 

Probiotics have been used safely for years. Safety outcomes are inconsistently reported in published clinical trials. In 2011, a report released by the Agency for Healthcare Research and Quality concluded that, although the existing probiotic clinical trials reveal no evidence of increased risk, "the current literature is not well equipped to answer questions on the safety of probiotics in intervention studies with confidence." Critics point out that the preponderance of evidence, including the long history of safe probiotic use as well as data from clinical trials, and animal and in vitro studies all support the assumption that probiotics are generally safe for most populations. Theoretical risks have been described in case reports, clinical trial results and experimental models, include systemic infections, deleterious metabolic activities, excessive immune stimulation in susceptible individuals, gene transfer and gastrointestinal side effects. More research is needed to properly describe the incidence and severity of adverse events related to probiotics

Recent studies exhibits probiotics will play an important role in future and will provide benefits that it will ultimately bring a major change in the structure of world population providing opportunity to health decision makers have an opportunity to make important strides in the area of probiotic research. Further, a robust pipeline of strain specific benefits that probiotics accrue at a local level is needed to ensure that they are safely, swiftly and successfully delivered to everyone who needs them.

The application of probiotics in dairy products is already common. However, the food industry is seeking to produce different varieties of probiotic foods other than dairy products with potential health benefits.  Microencapsulation technologies on another hand have provided the necessary protection for probiotics and moved them outside the pharmaceutical and supplemental use to become food ingredients. Microencapsulation technology has the potential to maintain the viability of probiotic bacteria during food product processing and storage. It is important that encapsulation keeps the probiotics active through the gastrointestinal tract and releases them in their target organ. The survival of microencapsulated cells in simulated gastric conditions is therefore also reviewed. Polysaccharides like alginate, gellan, κ-carrageenan and starch are the most commonly used materials in microencapsulation of bifidobacteria and lactobacilli.

Probiotics are microorganisms that are believed to provide health benefits when consumed.The term probiotic is currently used to name ingested microorganisms associated with benefits for humans and animals. A significant expansion of the potential market for probiotics has led to higher requirements for scientific substantiation of putative benefits conferred by the microorganisms.There are numerous claimed benefits of using commercial probiotics, such as reduction of gastrointestinal discomfort or strengthening of the immune system, such claims are not backed by scientific evidence.Yet one systematic review of 15 human randomized controlled trials from July 2016 found that certain commercially available strains of probiotic bacteria from the Bifidobacterium and Lactobacillus genera, when taken by mouth in daily doses of 10⁹–10¹⁰ colony forming units (CFU) for 1–2 months, possess treatment efficacy (i.e., improved behavioral outcomes) in certain psychological disorders, e.g. anxiety, depression, autism spectrum disorder, and obsessive-compulsive disorder – and improved certain aspects of memory.