A Review on the Effects of Functional Food on Humans and Microorganisms

Introduction

There is an old Chinese thought meaning that medicine and food are isogenic. In Japan, a national research project started to endorse the thought scientifically, In the 1980s, as the ageing society began to manifest itself in many countries of the world, prompt increases in the so-called life-style related diseases be¬came a matter of public concern [1]. Growing awareness was then observed of the need for eating to beat the odds. The pur¬pose was to prevent life-style related diseases such as diabetes, arterio, sclerosis, osteoporosis, allergies, cancer, and even some kinds of infectious diseases which recently includes COVID-19, through improved dietary practices in daily life. This gave a strong impetus to food science in Japan hence, the terminology and concept of “Functional foods” were first proposed [1]. Func¬tional foods according to the European Consensus provided the commonest and most recent definition, which states that ‘a food can be regarded as functional if it is satisfactorily demonstrated to affect beneficially one or more target functions in the body, beyond adequate nutritional effects, in a way that is relevant to either improved stage of health and well-being and/or reduction of risk of disease [2].

Research and discovery have been made in reaction to the find¬ing of functional foods over the years, and each year there is new information revealed. Researchers from the various fields of Nutrition, Pharmaceutical, Microbiology, Dairy sciences, Medical sciences and Food sciences are reporting their research findings on many interesting characteristics of food components in terms of their physiological functions. Functional foods are now acknowledged by the group of customers who are inter¬ested in following healthy food choices and nutritional benefits. In a nutshell, functional foods are the healthy food products of the future.one of the problems in the world most especially in rural areas the development of functional foods and nutraceuti¬cals from different ingredients and retention of these functional ingredients in different food products have not been adequately investigated. There are several articles on functional foods, but the novelty and importance of this review are to correlate the health effects of different component and bring them together in a concise description.

Functional Foods

Functional foods, also known as nutraceuticals, are defined as foods containing bioactive compounds that have beneficial ef¬fects on consumer health. Bioactive compounds are phytochem¬icals extracted and consumed as supplements or may have me¬dicinal value when engulfed as whole food. Functional food has gained popularity to prevent numerous diseases, boost growth, and enhance host metabolic activity. In addition, such function¬al foods may be useful for preventing communicable such like Covid-19 and non-communicable diseases [3].

Public health authorities consider prevention and treatment with nutraceutical as a powerful instrument in maintaining health and to act against nutritionally induced acute and chronic diseases, thereby promoting optimal health, longevity and quality of life. Recent studies have demonstrated that diets high in antioxidants shield people from degenerative illnesses like cancer, diabetes, cardiovascular disease, and neurodegenerative conditions like Parkinson's disease, Alzheimer's disease, multiple sclerosis, and amyotrophic lateral sclerosis caused by free radicals. Prior to attacking cells, free radicals can be stabilized or deactivated by antioxidants. They can also chelate metal catalysts, activate an¬tioxidant enzymes, reduce -tocopherol radicals, and block oxi-dases. They are thought to be the first line of Défense against free radical damage, making them essential for maintaining optimal cellular and systemic health and wellbeing [4]. It was discovered in Japan that a rice bran extract treated with a mixed Lactoba¬cillus-Saccharomyces culture generates a significant amount of g-amino butyric acid as a beneficial food component for lower¬ing the risk of hypertension and neurological problems, however the product has not yet been authorized [1]. The conventional approach to generating functional foods is to maximize elements that are beneficially functional and that regulate the immuno¬logical, endocrine, nervous, circulatory, or digestive systems of the body. But occasionally, a novel strategy can be used, and this strategy could result in the prevention of chronic disease [5]. An example is sulfur, it is essential for the health of plants and is an indispensable dietary component for human health and disease prevention Uniqueness is discovered in the reduction of unfavourable functional aspects by genetic engineering or even enzyme technology. Since the first study started in 1984, the sig-nificance of applying this idea to the design and production of functional foods has been underlined [6, 1].

Medical Importance of Functional Foods

The amazing potential of functional foods produced from nat-ural resources to treat some chronic diseases has been demon-strated by the growing number of research articles published in the previous several decades [1]. A food product can only be termed functional if all its properties has beneficial effects on human health by either improving the general and physical con¬ditions and/or decreasing the risk of the evolution of infectious diseases [7].

Functional foods have been attributed with anti-inflammatory properties. As a result, consumers' interest in the relationship between health, disease prevention, and well-being has signifi-cantly increased globally. The reservoirs from which functional foods, nutraceutical, and biomedical goods are derived can be found both in terrestrial and marine environments. Terrestri-al resources such as fruits, vegetables, cereals, probiotics, and mushrooms; however, is by far more explored than the marine resources even though the majority of those products in the mar-ketplace are of terrestrial origin, marine organisms-based prod-ucts are gaining attention due to their unique features, which are not found in terrestrial based metabolites for example the sea cucumbers [8].

Functional ingredients from sea cucumbers have become an increasingly interesting way to develop new foods as well as biomedicine products. Sea cucumbers are a source of high val¬ue-added compounds with health effects to be used as functional ingredients. Bioactive peptides, vitamins, minerals, fatty acids, saponins, carotenoids, collagens, gelatins, chondroitin sulfates, amino acids, fatty acids and other bioactive compounds are ex¬ample of such sea cucumber derived functional ingredients that can be added at different stages of the food and biomedicine pro¬duction process [8].

Of all the plant secondary metabolites, phenolic compounds have been extensively studied and are commonly used as an¬tioxidants for a wide range of applications. Several vegetables, particularly medicinal plants, have been widely studied for their natural antioxidant activity. They can act as suitable natural an¬tioxidants to replace synthetic ones and interfere with the oxi¬dation process and the alteration of lipids, proteins, and DNA. Natural antioxidants can also provide protection against degen¬erative diseases particularly cardiovascular diseases and cancer by inhibiting and scavenging free radicals function, for example the Tossa jute leaves is an example of the terrestrial habitat that contains high phenolic metabolites [9].

Fermented Foods

The many geographic regions where fermented foods are made have a variety of customs and cultural preferences. In temperate and cooler climates, fermentation helped our ancestors survive the winter, while it helped those in the tropics endure slumps. Fermentation is a metabolic process that uses organic compo¬nents as fuel without the use of an external oxidizer, from a bio¬chemical perspective [10]. Zymology is a term used frequently to refer to the scientific study of fermentation [11]. One of the first biotechnologies used to produce food products with bene¬ficial qualities including good organoleptic characteristics and a long shelf life is fermentation for instance, fermentation creates lactic acid, which is utilized to preserve foods like sour foods like yoghurt, kimchi, and pickled cucumbers [12]. The micro-biological stability and safety of finished fermented foods are typically increased, and some can even be stored at room tem¬perature. The term "fermentation" is also used widely to refer to the mass growth of microorganisms on a growth medium, fre¬quently in order to produce specialized chemicals like vaccines, antibiotics, enzymes, and addictive foods [12].

Types of Fermentation

According to the final products formed, Fermentation can be cat-egorized into;

• Lactic acid fermentation

• Acetic acid fermentation

• Butyric acid fermentation

• Alcohol acid fermentation

Lactic and Fermentation

Lactic acid fermentation is a bacterial process that happens during the production of food products variety. The lactic acid bacteria (LAB) are one type of bacterium capable of lactic mat¬uration (i.e. they produce lactic acid in relatively large amount from carbohydrates which serves as substrates). The primary metabolite produced during the maturation of sugars by the lac¬tic corrosive microorganisms is lactic acid, which emerged in the 20th century to represent a heterogeneous collection of micro-scopic organisms that are anaerobic, gram-positive, appear rod-shaped formed, non-sporulating, catalase-negative, aerotolerant, stationary, and are the makers of sugars [13].

Depending on the LAB species, the substrate, and the ambient factors, variations in the lactose metabolism's metabolic prod-ucts have led to the two main kinds of fermentation, homofer-mentation and heterofermentation. Lactic acid is the principal byproduct of homofermentative pathways, whereas acetic acid, ethanol, and carbon dioxide are among other metabolites pro¬duced by heterofermentative metabolism. A homofermentative metabolism can also switch to a mixed-acid metabolism with a variety of metabolites under specific circumstances (carbon shortage, carbon surplus of slowly metabolized carbohydrates, aerobic conditions). Several fragrance molecules or scent pre¬cursors, including acetaldehyde, ethanol, and diacetyl, are among these metabolic byproducts [14].

Acetic Acid Fermentation

Acetobacter aceti convert ethanol into acetic acid during the production of acetic acid, which can be done both aerobically and anaerobically. Yeasts normally start this fermentation by converting glucose to ethyl alcohol. Grain and natural product starches and sugars deteriorate into vinegar and fixes with an unpleasant flavor. Acetobacter aceti are commonly found on plants, flowers, and fruits. These aerobic environments are rich in carbohydrates, sugar alcohols, and/or ethanol. This enables A. aceti to rapidly and incompletely oxidize these substrates into organic acids for energy production through a specific respira-tory chain. Consequently, an acidification of the environment takes place, thereby preventing the growth of competitors, while the producing cells possess several mechanisms to tolerate the acidity. Also, they can utilize the accumulated organic acids later to further sustain their growth. Acetobacter aceti cells capable of cellulose production form biofilms that allow their retention on the culture surface, which is favorable for the survival of these strictly aerobic bacteria. All these physiological features explain their occurrence and underlines their functional role in the production of diverse fermented foods and beverages such as Lambic beer, water kefir, kombucha, and cocoa.

Butyric and Fermentation

Obligate anaerobic bacteria of the genus Clostridium exhibit this sort of fermentation. This happens during the retting of jute fi-ber, the processing of tobacco and leather, and the use of rancid butter. Dietary fiber fermentation results in the production of bu¬tyric acid in the human colon. The colonic epithelium relies on it as a significant source of energy. Glycolysis converts sugar first into pyruvate, which is then further oxidized by the oxidoreduc-tase enzyme system to generate acetyl-CoA and produce Hyand CO2. Butyric acid is created after more acetyl-CoA reduction. A considerably higher production of energy results from this kind of fermentation. A total of three Adenosine triphosphate mole¬cules are created [13]

Biological Activities of Functional Foods

Anticancer Activities: Cancer is the leading cause of death around the world cancer is not only the first leading cause of death worldwide and accounting for 8.2 million deaths in 2012, but also has diet as one of the most important modifiable risk factors [15]. Anticancer activities from many functional food sources have been reported in years, the extracts of garlic, horse¬radish, currykale as well as green and black tea were the most ef¬fective in lowering the viability of ovarian cancer cells Function¬al foods [bioactive compounds] have been identified as one of the means of reducing the predisposition to cancer, extracts from beans, lettuce, oats, eggs, and various nuts reduced the activi¬ty of pita vastatin [16-18]. These functional foods may inhibit various stages in the process of cancer formation. The bioactive compounds in functional foods such as polyphenol compounds. An example is the ferulic acid which ia a polyphenol compound with proven anticancer properties the effects of ferulic acid on tongue carcinomas and preneoplastic lesions have been studied in rats. The findings of the workers describe that the rats fed with a diet containing ferulic acid at a dose of 0.5 g/kg and exposed with 4-nitroquinoline-1-oxide in drinking water for 5 weeks at a dose of 0.02 g/kg reduced the impact of the carcinogen sig¬nificantly [19]. The findings also reported that a significant reduction in oral cancer in the rat groups fed with ferulic acid compared with those that were exposed to carcinogens alone. This result suggests that ferulic acid has a preventive mechanism against oral cancer. In addition, some pharmacological proper¬ties in flavonoids are inhibitory to cell damage [16].

Black soybean (Glycine max) is a nutritious legume that is high in proteins, essential amino acids, dietary fiber, vitamins, miner¬als, anthocyanin, phenolic acids, isoflavones and flavones [20]. Different researchers proved its anticancer activities against dif¬ferent cancer types. For example, made a report that Saponin present in soybean has potent anti-proliferation activity in in-vi-tro coca mouse colon cancer cells (Figure 1). Fermented Soy foods are a beneficial and healthy alternative to animal proteins, which possess peptides active against human colon cancer, liver tumor cancer and breast cancer cells [16]. The peptides from the protein hydrolysates were tested against cancer cell lines em-ploying 3-(4,5-dimethyl thiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) colorimetric titre method. The fraction with the best activity (F2-c) was further purified and the amino acid sequence was known as Leu/Ile-Val-Pro-Lys (L/IVPK), which is a tetra peptide due to its combination of four peptide. Mo¬lecular studies indicated that the purified peptide (L/IVPK) had maximum effectiveness against four apoptosis-related proteins namely Bcl-2 caspase-3, caspase-7 and XIAP, through the hy¬drophobic activities and hydrogen bonds, while caspase-3 bind¬ing exhibited the greatest binding energy [21]. The tetrapeptide named peptide L/IVPK possessed antioxidant and anticancer activities against Hela, HepG2, and MCF-7 cancer cell lines, while a peptide obtained from high oleic acid soybean variety exhibited significant activity against colon, liver and blood can¬cer cell lines. The purified peptide L/IVPK, which possessed an¬ticancer and antioxidant activities, can be utilized as a functional food ingredient for prophylaxis in the prevention and treatment of cancer. The peptide obtained from high oleic acid soybean is suggested to be a value-added ingredient to enhance soy meal by-product (Figure 1) [22].

Figure 1: Antioxidant and anticancer activities from black soybean.

Antimicrobial Activities

The presence of phenolic compounds in plant extracts and/or essential oils has been linked to the antibacterial properties of those substances [21]. Essential oils (EOs) have been long rec-ognized for their antibacterial, antifungal, antiviral, insecticidal and antioxidant properties. Phenolic compounds, such as flavo¬nols, which are frequently found in green tea and fruits, have demonstrated antibacterial activity [16]. Studying the polyphe¬nol in teas revealed that they have an antibacterial effect that stopped the development of caries. The growth of Salmonella spp. and Escherichia coli was significantly inhibited by extracts from strawberries and raspberries [16]. Also, the antibacterial properties of plant oils and extracts have been used in a variety of applications, such as pharmaceuticals, alternative medicine, and natural therapy [16]. The possible antimicrobial activities of essential oil on bacterial cell is shown in Figure 2 below.

Essential oils are widely used in medicine and the food indus¬try for these purposes. The antimicrobial properties of EOs have been reported in several studies. In many cases the activity re-sults from the complex interaction between the different classes of compounds such as phenols, aldehydes, ketones, alcohols, esters, ethers or hydrocarbons found in EOs. Though in some cases, the bioactivities of EOs are closely related with the ac¬tivity of the main components of the oils. Several studies have found that a number of these compounds exhibited significant antimicrobial properties when tested separately [22]. It has been reported that EOs containing aldehydes or phenols, such as cin¬namaldehyde, citral, carvacrol, eugenol or thymol as major com- ponents showed the highest antibacterial activity, followed by EOs containing terpene alcohols. Other EOs, containing ketones or esters, such as β-myrcene, α-thujone or geranyl acetate had much weaker activity. While volatile oils containing terpene, hydrocarbons were usually inactive High antimicrobial activi¬ty of Thymus and Organum species has been attributed to their phenolic components such as thymol and carvacrol and those of Eugenia caryophillus, Syzygium aromaticum, Ocimum basi¬licum to eugenol [22].

Examples of Bioactive Compounds in Functional Foods

Carotenoids: Carotenoids, also known as carotenes, belong to the group of lipid-soluble hydrocarbons; and their oxygenated derivatives are called xanthophyll. Some carotenoids can be converted into retinoid exhibiting vitamin A activity also they are much more versatile as they are relevant in foods not only as sources of vitamin A, but also as natural pigments, antioxi¬dants, and health promoting compounds which is essential for humans [23]. The color of egg-yolk and some fish is also due to carotenoids. Some of the rich sources of carotenoids are carrots, plums, apricots, mangoes, cantaloupes, sweet potatoes, kale, spinach, cilantro (coriander), collard greens, fresh thyme, turnip greens, and winter squash and health benefits include; singlet oxygen quencher, enhancement of the immune system, inhi¬bition neuroblastoma tumor growth, protective effects against testicular and spermatozoa toxicity [24]. Importantly, the β-car-otene is a precursor of vitamin A which is needed for robust im¬mune system, healthy skin and mucous membranes, and good eye health and vision [25].

Figure 2: Possible mechanisms of essential oil in a bacterial cell

Flavonoids

The flavonoids form the largest and a diverse group of bioactive compounds, known as phytonutrients or phytochemicals, which are the major constituents of polyphenols and can be consid¬ered more into flavanols, flavones, is flavones, flavanones, an-thocyanin’s, flavanonols, and flavans (catechins and proantho-cyanidins) [24]. Each subgroup and its type of flavonoids have a distinctive range of plant source, functions, and health benefits. This collection of plant bioactive compounds is known to pos¬sess benefits to human health due to their identified antioxidant and anti-inflammatory effects. Flavonoids exist in every fruit and vegetable, and along with carotenoids, they are responsible for their unique colors. There are more than 6,000 different identi-fied types of flavonoids which are beneficial in human diet. Fla¬vonoids are generally soluble in water and grow in cell vacuoles. Their basic molecular structure is two benzene rings bonded to a three-carbon chain that forms a closed pyran ring. Flavonoids are ample in a range of fruits and vegetables. Its major sources include berries, leeks, ginger, grapefruit, carrot, apple, onion, broccoli, cabbage, kale, tomato, lemon, parsley, buckwheat, and legumes. Coffee, tea, chocolate, a range of spices, herbs and red wine are also bursting with health-giving flavonoids. Many stud¬ies have revealed that a diet rich in phytonutrients is good for human health. Flavonoids are beneficial in this regard as they act as influential antioxidants; they also neutralize free radicals and limit damage to cells and other body tissues.

Terrenes

Terpenes are organic compounds that comprise the five-carbon isoprene building blocks, the cyclic molecule; monoterpene consists of two isoprene units, while terpenoids are a genre of secondary metabolites obtained from terpenes with several cy¬clic groups and oxygen. Terpenoids and terpenes are used sub¬stitution ally, but each has its own denotation. Terpenoids are terpenes with additional functional groups which are exception¬al such as the esters, carboxylic acids, and alcohols [23]. Ter¬penes and terpenoids are employed as flavouring agents in foods and as fragrances due to their volatilities. Terpenes are charac¬teristically volatile while terpenoids are either non-volatile or semi-volatile. These BACs are found in plant-based foods where they elicit medicinal properties and activities. The synergistic activities of these natural compounds enhance the psychological and physiological activities in humans. Hence, the many plants with these compounds are essential in the diet where they boost the potential endocannabinoid system directly or indirectly. The vital compounds present as terpenes and terpenoids in foods act as essential oils, cannabidiol (CBD), cannabigerol (CBG), and tetrahydrocannabinol (THC). The CBD groups act as an anti-inflammatory and analgesic, blocks hepatic carcinogenesis by aflatoxin, and aids in the regaining memory loss by acetyl cholinesterase’s inhibition, THC acts as local anaesthesia and sedative, improves gastro-oesophageal reflux, while CBG up regulates the gamma (γ)-aminobutyric acid compositions and as an anti-dermatophyte. Foods containing terpenes and terpenoids include lemon, lemongrass, lavender, pepper, orange, green tea, bay leaves, basil, pine, pine nuts, etc.

Functionality of Probiotic Foods

Probiotic Definition: The term "probiotic" was originally used in 1965 by Lilly and Stillwell to refer to substances generated by one organism that promote the growth of another [26]. Pro¬biotics are living microorganisms that, when given to the host in large enough doses, produce beneficial physiological effects. Due to their positive health effects, some lactic acid bacteria are typically considered to be safe and are categorized as probiotics in foods like yogurt, cheese, and pickles that have undergone fermentation. It was proposed that probiotics should be taken daily in levels of 108 to 1010 CFU to promote human health.

Prebiotics are non-digestible dietary ingredients that benefit the host by selectively triggering one or more colonic bacteria with probiotic qualities. Prebiotics and probiotics are collectively re¬ferred to as synbiotics. Probiotic preparations most frequently contain microorganisms from the genera Lactobacillus, Bifido-bacterium, Escherichia, Enterococcus, Bacillus, and Streptococ¬cus [26].

Properties of Probiotics

The criteria of probiotics are given below. Five billion colony forming units per day have been suggested as the optimal dosage for at least five days to provide an adequate level of health ben¬efits the microorganisms used in probiotic preparations should be generally recognized as safe (GRAS), resistant to pancreatic juice, bile, and hydrochloric acid, have anti-carcinogenic activ¬ity, and stimulate the immune system. They should also have reduced intestinal permeability, produce lactic acid, and be able to survive both acidic conditions in the stomach and alkaline conditions in the duodenum [26]. Probiotic preparations utilize both isolated and combined cultures of living organisms [26].

Consideration for selecting an ideal probiotic candidate include cell viability, thus they must be resistant to low pH and acids. Besides, probiotics must be able to adhere to the gut epithelium to cancel the flushing effects of peristalsis. They should be able to interact or to send signals to the immune cells associated with the gut, be of human origin and be nonpathogenic. Viability and activity of probiotics during storage and when passing through the GIT must be considered [27].

Mechanisms of Action of Probiotics

Major Probiotic mechanisms of action include enhancement of the epithelial barrier, increased adhesion to intestinal mucosa, and concomitant inhibition of pathogen adhesion, competitive exclusion of pathogenic microorganisms, production of anti-mi-croorganism substances and modulation of the immune system [16].

Enhancement of the Epithelial Barrier

Major Probiotic mechanisms of action include enhancement of the epithelial barrier, increased adhesion to intestinal mucosa, and concomitant inhibition of pathogen adhesion, competitive exclusion of pathogenic microorganisms, production of anti-mi-croorganism substances and modulation of the immune system [28]. The intestinal epithelium is in permanent contact with lu¬minal contents and the variable, dynamic enteric flora. The in¬testinal barrier is a major defense mechanism used to maintain epithelial integrity and to protect the organism from the environ¬ment. Defenses of the intestinal barrier consist of the mucous layer, antimicrobial peptides, secretory IgA and the epithelial junction adhesion complex. Once this barrier function is disrupt¬ed, bacterial and food antigens can reach the sub mucosa and can induce inflammatory responses, which may result in intestinal disorders, such as inflammatory bowel disease. Consumption of non-pathogenic bacteria can contribute to intestinal barrier func¬tion, and probiotic bacteria have been extensively studied for their involvement in the maintenance of this barrier. However, the mechanisms by which probiotics enhance intestinal barrier function are not fully understood [28].

Probiotics in Immunoregulation

It has been demonstrated that probiotic bacteria have a lot of positive immunological and health impacts. They play a role in controlling the bacterial ecosystem and modulating immune cells in addition to improving the bioavailability of nutrients and maintaining general health [29]. In addition to enhancing health and nutritional absorption, they also play a role in regulating the bacterial environment and immune cell modules.

Dendritic cells (DCs) are expert antigen-presenting cells that coordinate innate and adaptive immunity throughout the course of infections, autoimmune disorders, and cancers [30]. Natural killer (NK) cells play a crucial role in the early immune response to viral infections, especially when it comes to the removal of virus-infected cells. Probiotic strains of Lactobacillus can cause DCs to release IL-12, which in turn prompts NK cells to release IFN-gamma, a cytokine crucial for the eradication of lung bac¬teria (S. aureus) and viruses. DC can be stimulated by the gut microbiome to prime these cells. In actuality, L. reuteri and L. casei stimulate IFN-gamma synthesis and activate pro-inflam-matory Th1 cells.

The first cells to come into touch with bacteria and viruses are monocytes, which are found in the peripheral circulation [30]. When probiotics are consumed or the gut microbiota interact with them, they develop into tissue macrophages and release a variety of cytokines. Macrophages release the pro-inflammatory cytokine IL-12, which prompts the release of IFN-gamma by CD4+ Th1 cells and natural killer cells, which is necessary for the destruction of viruses60. In addition, probiotic strains of L. acidophilus, B. bifidum, L. delbrueckii, and L. gasseri stimulate the production of IFN-alpha by monocytes. THP-161, a human monocyte cell line, produces more TNF-alpha, IL-6, and IL-8 in response to the probiotic L. paracasei DG. As recently noted, S. thermophilus induces TNF-alpha, IL-6, and IL-8 profile, which is necessary for antiviral actions [29]. Consuming probiotics has the goal of utilizing their advantages in a symbiotic or com-mensal connection with the gut bacteria. The most prominent probiotics found in functional foods and other fermented foods include Leuconostoc spp., Lactobacilli, Enterococci, and Bi¬fidobacteria. In addition to this category of lactic acid bacteria, yeasts such Saccharomyces spp. are also utilized as probiotics (REF).

Probiotic bacteria may be crucial in the control of intestinal and systemic immunity because of their capacity to stick to intestinal epithelial cells (IELs) and to modify and stabilize the makeup of gut flora. Dendritic cells (DCs), NK cells, monocytes, mac¬rophages, and, to a lesser extent, B cells may all be affected by probiotics in terms of how well they operate. Some probiotics, especially lactic acid bacteria (LABs), stick to the epithelial gut wall to facilitate their capture in the Peyer's patches, where they directly control DC activation and proliferation. The production of TNF-a and IL-6 by DCs as well as IL-10 and IL12 by myeloid DCs (mDCs), which support Th1-Th2/Treg polarization, can all be stimulated by probiotics. A number of LABs also encourage plasmacytoid DCs to produce IFN-and trigger IL-12 and TNF-a production, which leads to the maturation of DCs (pDCs). Through the release of cytokines like IL-12 and IL-15, which promote NK cell activation, proliferation, and cytotoxic activi¬ty, mature DCs are effective NK cell stimulators. Additionally, some probiotic strains can induce monocytes to create IL-12 and NK cells to produce that IFN-g (REF).

Probiotics in Allergic Disorder

The term “allergy” was introduced in 1906 by von Pirquet, who recognized that in both protective immunity and hypersensi¬tivity reactions, antigens had induced changes in reactivity. In recent decades, allergic illnesses have become a major global issue. Being one of the most prevalent causes of chronic illness that requires hospitalization, allergic disorders have a typical¬ly tremendous impact on healthcare systems and society. The start of mucosal/systemic immune responses is caused by pro-biotics' ability to influence the innate/acquired immune system [31]. Food allergy (FA) is now one of the most common chronic diseases of childhood often lasting throughout life and leading to significant worldwide healthcare burden [32]. One of the most frequent causes of chronic and hospitalized illness, allergic ill-nesses have a typically notable impact on healthcare systems and society. An insufficient immunological response of T helper (Th2) cell lymphocytes to environmental or dietary stimuli is a description of allergic disorders. When this response is trig-gered, interleukins (IL)-4, IL-5, IL-13, and IgE made particular¬ly for allergens are secreted. The expression of the transcription factors GATA-3 (Th2) and T-bet controls the stability of the Th1/ Th2 equilibrium (Th1) [31].

Probiotics may alter enterocytes' toll-like receptors and proteo-glycan recognition proteins which would activate dendritic cells and trigger a Th1 response. Th1 cytokine production is stimu-lated, which can reduce Th2 responses [33]. According to pe-diatric studies, probiotic administration in children with atopic diseases such atopic dermatitis increases IFN production and decreases IgE- and antigen-induced TN F-, IL-5, and IL-10 se-cretion [33].

However, in many cases of food allergy, probiotics and prebi-otics have emerged as potential therapeutic agents. This type of treatment is aimed to minimize inflammation and correct diverse allergic symptoms, which in turn leads to better management of allergic diseases. Probiotics and prebiotics enhance the tolero-genic microenvironment inside the gut, which is essential for the treatment of food allergies. The nutraceuticals-based treatments provide highly efficient as well as cost-effective. However, there are certain cases where probiotics and prebiotics may fail to treat food allergies.

Dietary prebiotics are typically those fibrous, indigestible sub-stances that pass through the upper gut to encourage the growth of probiotics. Indigestible FOS, a simple case study, is special¬ly digested by bifidobacteria and bacteroides among others as energy sources for reproduction in the gastrointestinal tract [2]. Indigestible FOS is composed of 1-kestose (GF2) and nystose (GF3). Based on a series of bacterial dynamics and the trans¬fer of their metabolites, this process modifies the gut ecology and stimulates the release of IgA, a crucial component of the intestinal immune system. The bigger GF3 molecule can boost intestinal bacteroides throughout the same procedure to promote IgA synthesis [2].

Fermented Food Probiotics

Probiotics has been packaged recently as functional foods. In fact, the market for probiotics is ever increasing in size, and consumers’ demands have risen spontaneously based on the im¬mune-enhancing benefits of probiotics. They are already being sold as conventional foods, dietary supplements, medical foods and drugs in the United States, and are often administrated in capsules, liquid or powder forms and used in the treatment or management of diseases done which is allergic diseases [2]. Several studies have shown that supplementation of probiotics to food provides several health benefits such as reduction of se¬rum cholesterol, improved gastrointestinal function, enhanced immune system, and lower risk of colon cancer [34]. Fermen¬tation of vegetables and fruits is a common practice to maintain and improve the nutritional and sensory features of food com¬modities. A great number of potential lactic acid bacteria (LAB) were isolated from various traditional naturally fermented foods. Asian traditional fermented foods are generally fermented by LAB such as Lactobacillus plantarum, L. pentosus, L. brevis, L. fermentum, L. casei, Leuconostoc mesenteroides, L. kimchi, L. fallax, Weissella confusa, W. koreenis, W. cibaria, and Pediococ-cus pentosaceus, which are considered as the probiotic source of the food practice. Availability of certain specific nutrients such as vitamins, minerals, and acidic nature of fruits and vegetables provides conducible medium for fermentation by LAB [34].

Fruit and Vegetable-Based Fermented Probiotics Foods

Lactic acid fermentation represents the easiest and the most suit¬able way for increasing the daily consumption of fresh-like veg¬etables and fruits. Fruits and vegetables are perishable foods be¬cause of their high-water activity and nutritional richness. These circumstances are fundamental and essential in tropical and subtropical countries because they encourage the growth of bac¬teria that cause deterioration. In addition to extending the time that fruits and vegetables can actually be consumed, lactic acid fermentation also enhances several beneficial qualities, such as nutritional content, flavor, and lethality. The lactic acid bacteria Lactobacillus plantarum, L. pentosus, L. brevis, L. acidophilus, L. fermentum, Leuconostoc fallax, and L. mesenteroides are among those found in fermented fruits and vegetables, making them a possible source of probiotics. There are many fruits and vegetable pigments such as flavonoids, carotenoids and anthocy¬anins which protect us from various diseases [35].

Vegetables and fruits are fundamental sources of water-solu-ble vitamins (vitamin C and group B vitamins), provitamin A, phytosterols, dietary fibers, minerals and phytochemicals for the human diet. Scientific evidences encouraged the consump¬tion of vegetables and fruits to prevent chronic pathologies such as hypertension, coronary heart diseases and the risk of stroke. Increased consumption of vegetables can increase the plasma antioxidant capacity and is associated with the lower risk of can¬cer in order to preserve and produce a wide variety of foods, lactic acid bacteria are used [35]. Examples include fermented fresh vegetables like cabbage (sauerkraut, Korean kimchi) and cucumbers (pickles).

Kimchi

Kimchi is the name given to various traditional fermented veg¬etables, which are emblematic of the Korean culture. Kimchi is mainly manufactured with Chinese cabbages (Brassica pekin-ensis) and radish, but other seasonings ingredients such as gar¬lic, green onion, ginger, red pepper, mustard, parsley, fermented seafood (jeotgal), carrot and salt may be used. Due to its nutri¬tional properties, kimchi was recently included in the list of the top five “World’s Healthiest Foods” (http://eating.health.com/ 2008/02/01/worlds-healthiest-foods-kimchi-korea/). These ben- eficial effects are attributed either to functional components (vi¬tamins, minerals, fiber and phytochemicals) or to fermentation by lactic acid bacteria. The main pickles are tongbaechu-kimchi, tongkimchi and bossam-kimchi. After soaking with water, cab¬bages are cut and placed into a salt solution (7% for 12 h), which favours an increase of the concentration of NaCl up to 4.0% of the total weight. Further, cabbages are rinsed several times with fresh water and drained. The fermentation is carried out by au-tochthonous lactic acid bacteria, which vary depending on the main ingredients, temperature (30° C) and concentration of salt. Usually, Leuconostoc mesenteroides starts the fermentation but it is suddenly inhibited by the increasing concentration of lactic acid. Acid-tolerant species such as Lactobacillus brevis domi-nate during the middle stage, being replaced by Lact. plantarum during late fermentation. Nevertheless, the best tasting kimchi is obtained before the overgrowth of Lact. plantarum and Lact. brevis, at an optimal pH of 4.5. After fermentation, kimchi is left to ripen for several weeks under refrigeration conditions.

Stalk Vegetables

The best examples to be given to stalk vegetables are celery and asparagus. They contain minerals and vitamins in proportion to the green color Asparagus is a particularly rich source of folic acid. Fruit and flower vegetables Broccoli, cauliflower, and ar¬tichoke are frequently consumed flowering vegetables. Brocco¬li is a good source of iron, phosphorus, vitamins A and C, and riboflavin. Cauliflower is also a good source of vitamin C. The nutritional value of the outer leaves of cauliflower and brocco¬li is much higher than the flower buds. They can be consumed raw in salads or cooked. Artichoke is a good source of minerals, especially potassium, calcium, and phosphorus, and has high di¬etary fiber content. Tomatoes and peppers are the most common fruit vegetables. Both are rich in vitamin C. Other fruit vegeta¬bles include cucumber, zucchini, and eggplant. A dark green or yellow color indicates high β-carotene content. The darker the yellow color, the higher the content of β-carotene. In cauliflower Erwinia carotovora can be found.

Safety of Probiotics

Probiotics' safety for human health is one of their most critical qualities and a deciding factor in choosing which ones to use. In specifically, the characterization of a probiotic strain is based on the absence of virulence factors and resistance to clinical or vet¬erinary antibi biotics. The identification of bacterial strains is es¬sential for both safety and efficacy reasons since different strains of the same species can have varied effects on the host. Although probiotics are "generally regarded as safe" (GRAS) and their use has expanded recently, numerous researches have produced con¬flicting findings regarding both their safety and clinical useful¬ness. In 2002, FAO/WHO created Operating Standards, which served as guidelines for all companies making probiotic goods These recommendations include.

The formulation of probiotic usage recommendations;

• Phase I, II, and III clinical studies to demonstrate health bene¬fits equivalent to or superior to accepted preventative or curative measures for a certain ailment or disease;

• Good manufacturing practices and the creation of items of high quality

• Investigations to determine the in-vivo mechanism of action

• Clear and informative labeling;

• Creation of probiotic organisms that can deliver vaccinations to hosts and/or probiotics that fight viruses;

• Expansion of effective strains to treat cancer, allergies, and the healing process after surgery or injury as well as the oral cavi¬ty, nasopharynx, respiratory tract, stomach, vagina, bladder, and skin.

Impact of Some Functional Foods on Specific Diseases

Fruits: There are scientific evidences encouraging the consump¬tion of fruits for disease prevention due to their high nutritive values and antioxidant activities.

Apple and Cardiovascular Disease

Apples (Fi are rich sources of selected micronutrients (e.g., iron, zinc, vitamins C and E) and polyphenols (e.g., procyanidins, phloridzin, 5′-caffeoylquinic acid) that can help in mitigating micronutrient deficiencies (MNDs) and chronic diseases. Essen¬tial or bioactive compounds in apples include macronutrients, vitamins, minerals, elements, flavanols, hydroxycinnamic acids, flavonols, dihydrochalcones, anthocyanins, and others. Numer¬ous studies over the last three decades have shown that these compounds in apples exhibit significant biological effects on im¬proving human health and this backs up the poplar saying, “an apple a day keeps the doctor away” The vitamins and minerals in apples also provide essential micronutrients that aid the normal functions of biological and biochemical reactions in the body [36]. For example, vitamins C and E in apples contribute to the total antioxidant potential widely attributed to the fruit by donat¬ing single hydrogen equivalents to free radicals rendering them stable and leading to their eventual detoxification.

Apple consumption for the prevention of cardiovascular dis¬eases CVDs) including coronary heart disease, stroke, athero¬sclerosis, hypertension, cerebrovascular, and so on, remain the number one health challenge and cause of mortality globally and accounted for close to 18 million deaths in 2017 alone [37]. This huge health burden, therefore, warrants urgent disease-management approaches to lower the prevalence and mortality. Dietary flavonoids were shown to exert an inverse relationship with CVD-associated mortality in prospective cohort studies supporting the recommendation that the regular consumption of fruit and vegetables may help in reducing the risk of developing CVD. The intake of apples decreased atherogenic cholesterol levels [38]. enhanced endothelial function and decreased the bone mass index in clinical trials. These collective research find¬ings could be crucial in preventing CVD. It has been suggested that the modulation of the gut micro- biota by apples should be considered a major link to its ability to reduce CVD risk markers [39].

Banana and Obesity

Banana and plantain (Figure 3) are monocotyledonous plants be¬longing to the genus Musa, family Musaceae, and order Zingi-berene’s. There are studies on banana fruit reporting their poten¬tial contribution to health promotion effects both in in vitro and in vivo models. The results suggest that phenolic compounds play an important role against a wide range of physiological disorders, e.g., obesity, cancer, diabetes, neurodegenerative im-pairments, cardiovascular disorders, gastrointestinal lesions, and bone damage [40].

Banana is of utmost liking preference crop in mature and edible form that is abode of starch as macromolecule and also embed¬ded with various micronutrient in it. Unripe banana is also of same interest because it is preferred by commercial exploitation as of available starch. Commercially and of course primarily it can be modified to resistant form to be

Figure 3: Pictorial view of banana

Functional in the way of slow digestibility and low blood gly-cemic index features. This is the reason why it is hit choices by the diabetics, obese and cardiovascular patients for maintenance of their health [41]. Bananas are good sources of starch, fibers, minerals (potassium, magnesium, phosphorus, manganese), and vitamin B6 for consumers. In addition, raw and mature banan¬as have a characteristic matrix of bioactive compounds such as phenolic, carotenoids, biogenic amines, and phytosterols, which are highly desirable in the diet as they have many positive effects on human health and well-being. Banana and plantain pulp and peel have the potential to be exploited in the food and pharma¬ceutical industries, mainly for their catechin and rutin content [42].

Pectinase Treated Probiotic Banana Juice

Traditionally the banana fruit, Musa paradisiaca is used for bet¬ter digestion, diarrhea, dysentery, intestinal lesions in ulcerative colitis, sprue, uremia, nephritis, gout, lower blood pressure, car¬diac disease, stronger bones. But, banana peels are considered as a waste, thrown without use. In fact, banana peels are nutri¬tionally good source for fiber, smagnesium, potassium, calcium, iron, vitamin B6, vitamin C, omega fatty acids, resistant starch, proteins, antioxidants, oxalates, phytates, saponins and also a good source of other types of fiber, such as pectin which is wa¬ter-soluble. But, it is reported that pectinase enzymes are mostly produced from yeast cultures by using pectin as a substrate in sub-merged fermentation (SMF) techniques. Banana peel con¬tains 35% weight of total banana fruit with a very much useful in production of valuable fermented products.

A study was carried out by in the investigation on effects of Saccharomyces cerevisiae probiotic yeast fermented from pecti-nase treated probiotic banana juice (PPBJ) on obesity induced by high fat diet (HFD) for 20 weeks which prone to develop hyperglycemia, hyperinsulinemia, hyperleptinemia, hypertri-glyceridemia and hepatic steatosis [43]. This study gave an in-sight to the action of pectinase treated probiotic banana juice (PPBJ) in prevention and management of the obesity induced insulin resistance, type 2 diabetes (T2D). The result gotten from the study concluded that the increased intestinal Saccharomyces cerevisiae yeast can switch synergetic antioxidant effect and to an antagonistic effect towards the lipid radicals and may induce synthesis of polyunsaturated fatty acids which have anti-obesity, antidiabetic, antioxidative stress, antioxidant and anti-hepatoste-atosis effect. The anti steatotic effect of PPBJ is associated with the enhancement in the antioxidant potential of the liver by re¬duction in the oxidative stress triggered by High fat diet (HFD). Banana juice increased the concentration of gut microbes and allowed the gut microbes to interact with the host’s liver tissues and to regulate its energy metabolism and also played a role in control of nutrient absorption and metabolism, the integrity of the gut barrier [43]. This investigation is the evidence, suggest¬ing the potential therapeutic action of pectinase treated probiotic banana juice on HFD induced obesity, obesity associated insu¬lin resistance lipid peroxidation and hepatic steatosis prevention and treatment [43].

Banana consumption and most importantly the peel can poten¬tially decrease the occurrence of different diseases since this fruit is rich in several bioactive compounds, such as secondary metabolites, minerals, and fibers. Additionally, new strategies to use banana biomasses have been employed, e.g., the extraction of bioactive compounds from different parts of the plant [41]. These extracts have been studied mostly for the determination of their antioxidant activity.

Herbs and Spies

Ginger and covid19: Ginger (Zingiber officinale Roscoe) (Fig¬ure 4) contains several components, including about 3.0%-6.0% fatty oil, 9.0% protein, 60.0%-70.0% carbohydrates, 3.0%-8.0% crude fiber, about 8.0% ash, 9.0%-12.0 % water and approxi¬mately 2.0% volatile oil the pharmacological effects of ginger are largely attributed to its terpenes and phenolic compounds [44]. Terpene ingredients of ginger include zingiberene, bisabo-lene, farnesene, sesquiphellandrene, limonene, cineole, linalool, borneol, geranial and curcumene. The ginger-derived phenolic compounds include gingerols, paradols, shogaols, and zing-erone. Ginger also contains other gingerol- or shogaol-related compounds such as 1- dehydrogingerdione, 6-gingerdione and 10-gingerdione as well as gingerdiols and diarylheptanoids. The major pungent ingredients of fresh ginger are gingerols. Al-though 6-gingerol is the most abundant gingerol in ginger, other types of gingerols, such as 8-, 10- and 12-gingerols as well as 6-gingerdione are also present [45]. Gingerol is a phenol phy-tochemical compound found in fresh ginger that activates spice receptors on the tongue. In vivo tests in rats that were immu-nosuppressed using cyclophosphamide showed that ginger es¬sential oil given once a day orally for a week could increase the humoral immune response. Humoral immunity involves interac¬tion between B-cells and antigens for subsequent proliferation and differentiation into plasma cells that secrete antibodies.

Coronavirus disease 2019 (COVID-19) is a type of disease caused by a virus from the coronavirus group, namely the severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2.1 COVID-19 can cause respiratory system disorders, ranging from dyspnea, fever, nonproductive cough, pneumonia, fatigue, and myalgia, emerge after an incubation stage of 2 to 14 days [46]. Currently, there are no specific therapies, such as relevant antivi-ral drugs, available for COVID-19 social distancing &boosting the body’s immune system may prevent the disease from spread¬ing [44]. Herbs can provide valuable sources of compounds that have immunomodulatory, anti-inflammatory, antioxidant, and antiviral properties, exerting beneficial effects on systems affect¬ed by viruses. Experimentally and clinically, ginger (the rhizome of Zingiber officinale) has exhibited numerous therapeutic ac¬tivities, including anti-inflammatory, antioxidant, immunomod¬ulatory, antimicrobial, antifungal, anticancer, neuroprotective, antimigraine, hepatoprotective, hypocholesterolemic, cardio-vascular protective, respiratory protective, antiobesity, antidia-betics, anti-nausea and anti-emetics [47].

Ginger Potential Activities Against Covid-19

According to the molecular docking analyses, it was also found that 6-gingerol (a component in ginger) exhibit a high binding affinity with a number of virus proteins (main protease, SARS-CoV3C like molecule and cathepsin K) which are essential for SARS-CoV-2 replication. 6-gingerol also binds to the S protein and several RNA binding proteins of SARS-CoV-2. Docking analyses also revealed that gingerol, geraniol, shogaol, zingi-berene, zingiberenol, and zingerone interact with key residues in the catalytic domain of the MPro. Meanwhile, geraniol, shogaol, zingiberene, zingiberenol and zingerone can interfere with S protein-ACE2 binding. Docking studies indicated that 6-gingerol, 8- gingerol, 10-gingerol, 10- shogaol, 8-paradol, and 10-paradol interact with the RBD of the virus S protein as well as human ACE2, thus they can inhibit the spreading of SARS-CoV-2.The results from a computational analysis indicate that a ginger-derived terpene namely sesquiphellandrene binds to S protein and thus interferes with the S protein-ACE2 interaction another reason is PL pro can be considered as a proper target of anti-SARS-CoV-2 drugs in order to effectively prevent virus replication and survival. Molecular docking approaches indicat¬ed that 8- gingerol, 10-gingerol, 6-gingerol and another class of the ginger's ingredients potently inhibit PLpro [48].

Some in vivo observations in a study in Saudi Arabia indicate the consumption of ginger by COVID-19 patients was increased from 36.2% prior infection to 57.6% after infection. The pro¬portion of patients’ hospitalization for COVID-19 treatment was also lower among ginger users (28.0%) than in non-users (38.0%) (REF).

In a study from Bangladesh, a few cases of cured COVID-19 pa¬tients were described who consumed home medicines contain¬ing ginger in mixes of various herbs with or without the use of additional treatments (REF). According to the results from a Tu¬nisian study, treatment of a few cases of COVID-19 with home medicines containing ginger in combinations with other herbs reduced disease symptoms. In some parts of Africa, acclaimed remedies containing ginger in mixes of various herbs were also used for the management of COVID-19 (REF).

The results from a clinical trial study from Iran indicate that a combination therapy by ginger and Echinacea in suspected COVID-19 outpatients attenuated some of their clinical symp¬toms (breath shortness, coughing and muscular pain) in compar¬ison with those treated with a standard protocol using hydroxy-chloroquine, alone (REF).

Figure 4: Zingiber officinale Roscoe

Cinnamon and Type 2 Diabetes

Cinnamon was derived from a Greek word that means sweet wood, comes from the inner bark of tropical evergreen cinna-mon trees (Figure 5) [47]. Cinnamon is a genus of the Lauraceae family, many of whose members are used as spices. It is one of the most widely used flavoring agents used in the food and bev¬erage industry worldwide and well recognized for its medicinal properties since antiquity and has recently become increasing¬ly popular for its benefits in glycemic control. It has been used for the treatment of coronary risk factors, particularly diabetes mellitus, and obesity, and for ameliorating dyslipidemia. Its leaf and bark have digestive, blood purifier, astringent, carminative, warming stimulant, antiseptic, antibacterial, antifungal, and an¬tiviral properties and can help to reduce cholesterol and blood sugar levels [49]. Different mechanisms of action have been suggested in the scientific literature for cinnamon and its bio-active compounds regarding their beneficial properties and this includes; Cinnamon mediate antidiabetic effects by preventing inflammation. In a study, it was found that treatment with cinna¬mon extract resulted in the decreased expression of interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α mRNA, while increasing the expression of IR, IRS1, IRS2, PI3K and Akt1 in hamster enterocytes Another potential mechanism of action of cinnamon extract involves the activation of the transcription fac¬tors, peroxisome proliferator-activated receptors (PPARs) [48]. PPARs have been shown to be involved in the regulation of in¬sulin resistance and adipogenesis, and PPAR agonists such as thiazolinediones have long been used clinically in the treatment of T2D and insulin resistance [50].

Figure 5: Structure and different presentations of Cinnamon

The major components found in cinnamon are identified as cin¬namaldehyde, procyanidin type-A polymers, cinnamic acid, and coumarin. The polyphenol-rich cinnamon has been demonstrat¬ed to be a potential source of natural antioxidants, exhibiting strong free radical scavenging properties in vitro, which may contribute to protecting against oxidative stress [50]. Moreover, cinnamon has been employed as a potential therapeutic agent to treat Type 2 diabetes mellitus, Type 2 diabetes mellitus (T2DM) is a major global health disorder, and it constitutes an import¬ant contribution to morbidity and mortality worldwide. Type 2 diabetes is defined as a complex metabolic disorder of insulin sensitivity and action on peripheral tissues like skeletal muscle and adipose tissue and of impaired insulin secretion this occurs in certain individuals as a result of lifestyle factors, such as diet and obesity, as well as genetic predisposition. Glycemic control presents a constant challenge for those with diabetes with this, cinnamon has demonstrated its effectiveness in decreasing fast¬ing blood glucose, serum lipids and insulin resistance improve¬ment, and the functionality to which cinnamon expresses its ef¬fect on blood glucose can be attributed to its active component cinnamaldehyde [51].

Studies on Cinnamon

A study was conducted on the effect of cinnamon on diabetic patients by on mainly 37 participatants, with no significant dif-ferences in baseline characteristics, dietary intake and physical activity between groups. In the treatment group, the levels of fasting blood glucose, HbA1c, triglyceride, weight, BMI and body fat mass decreased significantly compared to baseline, but not in placebo group. No significant differences were observed in glycemic status indicators, lipid profile and anthropometric indicators between the groups at the end of intervention. And the conclusion on the experimental study is that, the data sug¬gest that cinnamon may have a moderate effect in improving glycemic status indicators. Effects of cinnamon consumption on glycemic status, lipid profile and body composition in type 2 diabetic patients.

In a meta-analysis of 10 RCTs (n = 543 patients), cinnamon dos¬es of 120 mg/d to 6 g/d for 4 to 18 weeks reduced levels of fasting plasma glucose (−24.59 mg/dL; 95% CI, −40.52 to −8.67 mg/dL), total cholesterol (−15.60 mg/dL; 95% CI, −29.76 to −1.44 mg/dL), LDL-C (−9.42 mg/dL; 95% CI, −17.21 to −1.63 mg/dL), and triglycerides (−29.59 mg/dL; 95% CI, −48.27 to −10.91 mg/dL). Cinnamon also increased levels of HDL-C (1.66 mg/dL; 95% CI, 1.09 to 2.24 mg/dL). No significant effect on hemoglobin A1c levels (−0.16%; 95%, CI −0.39% to 0.02%) was seen. High degrees of heterogeneity were present for all analyses except HDL-C (I2 ranging from 66.5% to 94.72%).

Based on the experiment made the conclusion that was drawn is that the consumption of cinnamon is associated with a statis- tically significant decrease in levels of fasting plasma glucose, total cholesterol, LDL-C, and triglyceride levels, and an increase in HDL-C levels; however, no significant effect on hemoglobin A1c was found. The high degree of heterogeneity may limit the ability to apply these results to patient care, because the pre-ferred dose and duration of therapy are unclear [51-76]. Cinna¬mon use in type 2 diabetes: an updated systematic review and meta-analysis.

Conclusion

A food can be regarded as functional if it is satisfactorily demon¬strated to affect beneficially one or more target functions in the body. Functional foods have demonstrated efficacy in prevent¬ing and treating various medical conditions particularly those involving the gastrointestinal tract. For instance, the microbes in probiotic foods have the ability to manipulate the gut/lung microbiome and this is promising for the prevention/treatment of various diseases including COVID-19, owing to the immuno¬modulatory qualities associated with the probiotics and this has been an advantage in the field of medicine.

There is highly good possibility for the use of fruits, vegetables, herbs, spices and probiotics foods, consumed in right propor-tions, in the prevention or treatment of infectious disease owing to safety, effectiveness, and cheap cost. There is no denying that prioritizing our natural foods, we also support the overall health of our communities.

Recommendation

Locals are aware of the advantages of these bioactive substances in the treatment of disease, but precautions should be taken be¬fore consuming these foods in which they are not fully educated to know because, at high doses, some components become toxic and poisonous to human cells. There is still need for more stud¬ies on the safety and effectiveness of functional foods on health to draw more concrete statements. Thus, upcoming Microbiol-ogists should consider the field of food microbiology as more research is needed for the functions of natural bioactive foods in the field of medicine

References

1. Arai, S. (2002). Global view on functional foods: Asian per­spectives. British Journal of Nutrition, 88(S2), S139-S143.
2. Ashaolu, T. J. (2020). Immune boosting functional foods and their mechanisms: A critical evaluation of probiot­ics and prebiotics. Biomedicine & Pharmacotherapy, 130, 110625.
3. Swarnakar, R., Yadav, S. L. (2022). Communicable to Non-communicable Disease Pandemic in the Making: An Urgent Call for Post-COVID-19 Preparedness. Cureus, 14(7).
4. Adefegha, S. A. (2018). Functional foods and nutraceuticals as dietary intervention in chronic diseases; novel perspec­tives for health promotion and disease prevention. Journal of dietary supplements, 15(6), 977-1009.
5. Birch, C. S., Bonwick, G. A. (2019). Ensuring the future of functional foods. International Journal of Food Science & Technology, 54(5), 1467-1485.
6. Hill, C. R., Haoci Liu, A., McCahon, L., Zhong, L., Shafaei, A., et al. (2023). S-methyl cysteine sulfoxide and its poten­tial role in human health: a scoping review. Critical Reviews in Food Science and Nutrition, 1-14.
7. Luvián-Morales, J., Varela-Castillo, F. O., Flores-Cisneros, L., Cetina-Pérez, L., Castro-Eguiluz, D. (2022). Functional foods modulating inflammation and metabolism in chron­ic diseases: A systematic review. Critical Reviews in Food Science and Nutrition, 62(16), 4371-4392.
8. Pangestuti, R., Arifin, Z. (2018). Medicinal and health bene­fit effects of functional sea cucumbers. Journal of traditional and complementary medicine, 8(3), 341-351.
9. Yakoub, A. R. B., Abdehedi, O., Jridi, M., Elfalleh, W., Nas-ri, M., et al. (2018). Flavonoids, phenols, antioxidant, and antimicrobial activities in various extracts from Tossa jute leave (Corchorus olitorus L.). Industrial Crops and Prod­ucts, 118, 206-213.
10. Liu, X., Yu, X. (2020). Enhancement of butanol production: from biocatalysis to bioelectrocatalysis. ACS Energy Let­ters, 5(3), 867-878.
11. Vilela, A. (2019). The importance of yeasts on fermentation quality and human health-promoting compounds. Fermen­tation, 5(2), 46.
12. Adesulu-Dahunsi, A. T., Dahunsi, S. O., Olayanju, A. (2020). Synergistic microbial interactions between lactic acid bacteria and yeasts during production of Nigerian in­digenous fermented foods and beverages. Food Control, 110, 106963.
13. Kårlund, A., Gómez-Gallego, C., Korhonen, J., Palo-Oja,O. M., El-Nezami, H., et al. (2020). Harnessing microbes for sustainable development: Food fermentation as a tool for improving the nutritional quality of alternative protein sources. Nutrients, 12(4), 1020.
14. Chen, Z., Li, W., Santhanam, R. K., Wang, C., Gao, X., et al. (2019). Bioactive peptide with antioxidant and antican­cer activities from black soybean [Glycine max (L.) Merr.] byproduct: Isolation, identification and molecular docking study. European Food Research and Technology, 245, 677-689.
15. Zeng, Y. W., Du, J., Pu, X. Y., Yang, J. Z., Yang, T., et al. (2015). Coevolution between human's anticancer activities and functional foods from crop origin center in the world. Asian Pacific Journal of Cancer Prevention, 16(6), 2119-2128.
16. Banwo, K., Olojede, A. O., Adesulu-Dahunsi, A. T., Ver­ma, D. K., Thakur, M., et al. (2021). Functional importance of bioactive compounds of foods with Potential Health Benefits: A review on recent trends. Food Bioscience, 43, 101320.
17. Furdak, P., PieÅ?kowska, N., Bartosz, G., Sadowska-Barto-sz, I. (2022). Extracts of Common Vegetables Inhibit the Growth of Ovary Cancer Cells. Foods, 11(16), 2518.
18. Jawad, M. J., Ibrahim, S., Kumar, M., Burgert, C., Li, W. W., et al. (2022). Identification of foods that affect the anti cancer activity of pitavastatin in cells. Oncology Letters, 23(3), 1-8.
19. El-Gogary, R. I., Nasr, M., Rahsed, L. A., Hamzawy, M. A. (2022). Ferulic acid nanocapsules as a promising treatment modality for colorectal cancer: Preparation and in vitro/in vivo appraisal. Life sciences, 298, 120500
20. Kumar, M., Suhag, R., Hasan, M., Dhumal, S., Radha, Pan-diselvam, R., et al. (2023). Black soybean (Glycine max (L.) Merr.): paving the way toward new nutraceutical. Critical Reviews in Food Science and Nutrition, 63(23), 6208-6234.
21. Chen, Y., Liu, Q., Guo, D. (2020). Emerging coronaviruses: genome structure, replication, and pathogenesis. Journal of medical virology, 92(4), 418-423.
22. Bassolé, I. H. N., Juliani, H. R. (2012). Essential oils in combination and their antimicrobial properties. Molecules, 17(4), 3989-4006.
23. Meléndez-Martínez, A. J., MandiÄ?, A. I., Bantis, F., Böhm, V., Borge, G. I. A., et al. (2022). A comprehensive review on carotenoids in foods and feeds: Status quo, applications, patents, and research needs. Critical Reviews in Food Sci­ence and Nutrition, 62(8), 1999-2049.
24. Maghsoudi, S., Taghavi Shahraki, B., Rabiee, N., Fatahi, Y., Bagherzadeh, M., et al. (2022). The colorful world of carot­enoids: A profound insight on therapeutics and recent trends in nano delivery systems. Critical reviews in food science and nutrition, 62(13), 3658-3697.
25. Ramos da Silva, L. R., Ferreira, O. O., Cruz, J. N., de Jesus Pereira Franco, C., Oliveira dos Anjos, T., et al. (2021). La-miaceae Essential.
26. Gupta, V., Garg, R. (2009). Probiotics. Indian journal of medical microbiology, 27(3), 202-209.
27. Shi, L. H., Balakrishnan, K., Thiagarajah, K., Ismail, N. I. M., Yin, O. S. (2016). Beneficial properties of probiotics. Tropical life sciences research, 27(2), 73.
28. Bermudez-Brito, M., Plaza-Díaz, J., Muñoz-Quezada, S., Gómez-Llorente, C., Gil, A. (2012). Probiotic mechanisms of action. Annals of Nutrition and Metabolism, 61(2), 160-174.
29. Olaimat, A. N., Aolymat, I., Al-Holy, M., Ayyash, M., Abu Ghoush, M., et al. (2020). The potential application of pro­biotics and prebiotics for the prevention and treatment of COVID-19. npj Science of Food, 4(1), 17.
30. Kvedaraite, E., Ginhoux, F. (2022). Human dendritic cells in cancer. Science immunology, 7(70), eabm9409.
31. Eslami, M., Bahar, A., Keikha, M., Karbalaei, M., Koby-liak, N. M., et al. (2020). Probiotics function and modula­tion of the immune system in allergic diseases. Allergologia et Immunopathologia, 48(6), 771-788.
32. Castellazzi, A. M., Valsecchi, C., Caimmi, S., Licari, A., Marseglia, A., et al. (2013). Probiotics and food allergy. Italian Journal of Pediatrics, 39(1), 1-10.
33. Michail, S. (2009). The role of probiotics in allergic diseas­es. Allergy, Asthma & Clinical Immunology, 5(1), 1-7.
34. Swain, M. R., Anandharaj, M., Ray, R. C., Rani, R. P. (2014). Fermented fruits and vegetables of Asia: a potential source of probiotics. Biotechnology research international, 2014.
35. Pandey, G., Madhuri, S. (2010). Significance of fruits and vegetables in malnutrition cancer. Plant Arch, 10(2), 517-22.
36. Oyenihi, A. B., Belay, Z. A., Mditshwa, A., Caleb, O. J. (2022). “An apple a day keeps the doctor away”: The po­tentials of apple bioactive constituents for chronic disease prevention. Journal of Food Science, 87(6), 2291-2309.
37. Virani, S. S., Alonso, A., Benjamin, E. J., Bittencourt, M. S., Callaway, C. W., American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. (2020). Heart disease and stroke statistics—2020 update: a report from the American Heart Association. Circulation, 141(9), e139-e596.
38. Chai, S. C., Hooshmand, S., Saadat, R. L., Payton, M. E., Brummel-Smith, K., et al. (2012). Daily apple versus dried plum: impact on cardiovascular disease risk factors in post-menopausal women. Journal of the Academy of Nutrition and Dietetics, 112(8), 1158-1168.
39. Koutsos, A., Tuohy, K. M., Lovegrove, J. A. (2015). Apples and cardiovascular health—is the gut microbiota a core con­sideration? Nutrients, 7(6), 3959-3998.
40. Rodríguez-Morató, J., Xicota, L., Fitó, M., Farré, M., Di-erssen, M., et al. (2015). Potential role of olive oil phenolic compounds in the prevention of neurodegenerative diseas­es. Molecules, 20(3), 4655-4680.
41. Dhull, S. B., Malik, T., Kaur, R., Kumar, P., Kaushal, N., et al. (2021). Banana starch: Properties illustration and food applications—A review. Starchâ?Stärke, 73(1-2), 2000085.
42. Dhull, S. B., Malik, T., Kaur, R., Kumar, P., Kaushal, N., et al. (2021). Banana starch: Properties illustration and food applications—A review. Starchâ?Stärke, 73(1-2), 2000085.
43. Konda, P. Y., Poondla, V., Jaiswal, K. K., Dasari, S., Uyyala, R., et al. (2020). Pathophysiology of high fat diet induced obesity: impact of probiotic banana juice on obesity associ­ated complications and hepatosteatosis. Scientific Reports, 10(1), 16894.
44. Utami, A. T., Qarrah, A. G. A. (2022). Benefi ts of Ginger as Medicine for COVID-19: Literature Study. Journal ISSN, 2766, 2276.
45. Jafarzadeh, A., Jafarzadeh, S., Nemati, M. (2021). Ther­apeutic potential of ginger against COVID-19: Is there enough evidence? Journal of Traditional Chinese Medical Sciences, 8(4), 267-279.
46. Hidayat, R., Wulandari, P. (2023). The Herbal Potential of Ginger (Zingiber officinale Roscoe) and Guava (Psidium guajava L.) as Supplements for the Management of Corona­virus Disease 2019 (COVID-19). Eureka Herba Indonesia, 4(1), 167-170.
47. Sharma, P. K., Shankhdhar, P. K., Gangwar, A., Pathak, N. (2022). Ginger: Plant Immuno-booster against COVID-19. 2022.100605. World Journal of Pharmaceutical Sciences, 92-99.
48. Medagama, A. B. (2015). The glycaemic outcomes of Cin­namon, a review of the experimental evidence and clinical trials. Nutrition journal, 14, 1-12.
49. Rafehi, H., Ververis, K., Karagiannis, T. C. (2012). Contro­versies surrounding the clinical potential of cinnamon for the management of diabetes. Diabetes, Obesity and Metab­olism, 14(6), 493-499.
50. Silva, M. L., Bernardo, M. A., Singh, J., de Mesquita, M.F. (2022). Cinnamon as a complementary therapeutic ap­proach for dysglycemia and dyslipidemia control in type 2 diabetes mellitus and its molecular mechanism of action: A review. Nutrients, 14(13), 2773.
51. Allen, R. W., Schwartzman, E., Baker, W. L., Coleman, C. I., Phung, O. J. (2013). Cinnamon use in type 2 diabetes: an updated systematic review and meta-analysis. The Annals of Family Medicine, 11(5), 452-459.
52. Acidereli, H., KarataÅ?, Y., Burhan, H., Gülcan, M., Å?en, F. (2021). Magnetic nanoparticles. In Nanoscale processing (pp. 197-236). Elsevier.
53. Aderiye, B. I., Laleye, S. A. (2003). Relevance of fermented food products in southwest Nigeria. Plant Foods for Human Nutrition, 58, 1-16.
54. Bondonno, N. P., Bondonno, C. P., Blekkenhorst, L. C., Considine, M. J., Maghzal, G., et al. (2018). Flavonoid�rich apple improves endothelial function in individuals at risk for cardiovascular disease: a randomized controlled clinical trial. Molecular nutrition & food research, 62(3), 1700674.
55. Boyer, J., Liu, R. H. (2004). Apple phytochemicals and their health benefits. Nutrition journal, 3, 1-15.
56. Dargahi, N., Johnson, J., Donkor, O., Vasiljevic, T., Apos-tolopoulos, V. (2019). Immunomodulatory effects of probi­otics: Can they be used to treat allergies and autoimmune diseases?. Maturitas, 119, 25-38.
57. de Roock, S., van Elk, M., Hoekstra, M. O., Prakken, B. J., Rijkers, G. T., et al. (2011). Gut derived lactic acid bacte­ria induce strain specific CD4+ T cell responses in human PBMC. Clinical Nutrition, 30(6), 845-851.
58. Di Cagno, R., Filannino, P., Cantatore, V., Polo, A., Celano, G., et al. (2020). Design of potential probiotic yeast start­ers tailored for making a cornelian cherry (Cornus mas L.) functional beverage. International journal of food microbi­ology, 323, 108591.
59. Gayer, B. A., Avendano, E. E., Edelson, E., Nirmala, N., Johnson, E. J., et al. (2019). Effects of intake of apples, pears, or their products on cardiometabolic risk factors and clinical outcomes: A systematic review and meta-Analysis. Current Developments in Nutrition, 3(10), nzz109.
60. Gibson, G. R., Hutkins, R. W., Sanders, M. E., Prescott, S. L., Reimer, R. A., et al. (2017). The International Scientific Association for Probiotics and Prebiotics (ISAPP) consen­sus statement on the definition and scope of prebiotics.
61. Halliwell, B. (2006). Reactive species and antioxidants. Re-dox biology is a fundamental theme of aerobic life. Plant physiology, 141(2), 312-322.
62. Lastochkina, O., Aliniaeifard, S., SeifiKalhor, M., Bosac-chi, M., Maslennikova, D., et al. (2022). Novel approaches for sustainable horticultural crop production: Advances and prospects. Horticulturae, 8(10), 910.
63. Ketnawa, S., Reginio Jr, F. C., Thuengtung, S., Ogawa, Y. (2022). Changes in bioactive compounds and antioxidant activity of plant-based foods by gastrointestinal digestion: A review. Critical reviews in food science and nutrition, 62(17), 4684-4705.
64. Khan, A., Safdar, M., Ali Khan, M. M., Khattak, K. N., Anderson, R. A. (2003). Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes care, 26(12), 3215-3218.
65. Kim, Y., Je, Y. (2017). Flavonoid intake and mortality from cardiovascular disease and all causes: A meta-analysis of prospective cohort studies. Clinical nutrition ESPEN, 20,68-77.
66. Leontowicz, H., Gorinstein, S., Lojek, A., Leontowicz, M., Ä?ı́ž, M., et al. (2002). Comparative content of some bioac­tive compounds in apples, peaches and pears and their influ­ence on lipids and antioxidant capacity in rats. The Journal of nutritional biochemistry, 13(10), 603-610.
67. Angu, T. C., Ngwasiri, P. N., Navti, L. K., Yimta, D. Y., Angaba, F. F. A. (2023). Preservation Potentials of Essential Oils of Ocimum basilicum and Ocimum gratissimum from Two Agro-Ecological Zones on Freshwater Smoke-Dried Oreochromis niloticus Fish Sold in Some Local Markets in Cameroon. Advances in Biological Chemistry, 13(5), 192-207.
68. Phiri, S., Schoustra, S. E., van den Heuvel, J., Smid, E. J., Shindano, J., et al. (2020). How processing methods affect the microbial community composition in a cereal-based fer­mented beverage. LWT, 128, 109451.
69. Pietta, P. G. (2000). Flavonoids as antioxidants. Journal of natural products, 63(7), 1035-1042.Harrop, G. A., & Struve,M. (1934). The banana in the management of obesity. The American Journal of Nursing, 685-694.
70. Ranjha, M. M. A. N., Irfan, S., Nadeem, M., Mahmood, S. (2022). A comprehensive review on nutritional value, me­dicinal uses, and processing of banana. Food Reviews Inter­national, 38(2), 199-225.
71. Rasool, N., Saeed, Z., Pervaiz, M., Ali, F., Younas, U., et al. (2022). Evaluation of essential oil extracted from ginger, cinnamon and lemon for therapeutic and biological activi­ties. Biocatalysis and Agricultural Biotechnology, 102470.
72. Salem-Bekhit, M. M., Moussa, I. M. I., Muharram, M. M., Alanazy, F. K., Hefni, H. M. (2012). Prevalence and antimi­crobial resistance pattern of multidrug-resistant enterococci isolated from clinical specimens. Indian journal of medical microbiology, 30(1), 44-51.
73. Selvamuthukumaran, M. (2022). Seafood Based Functional Foods. Functional Foods, 289-301.
74. Thenmozhi, P., Bhuvaneshwari, S. (2022). Cinnamon and Diabetes: Efficacy on Blood Glucose Level in Patients with Type 2 Diabetes. Trends in Biomaterials & Artificial Or­gans, 36.
75. Ülger, T. G., Songur, A. N., Çırak, O., ÇakıroÄ?lu, F. P. (2018). Role of vegetables in human nutrition and disease prevention. Veg. Importance Qual. Veg. Hum. Health, 7-32.
76. Virani, S. S., Alonso, A., Benjamin, E. J., Bittencourt, M. S., Callaway, C. W., et al. (2020) American Heart Association Council on Epidemiology and Prevention Statistics Com­mittee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2020 update: a report from the Amer­ican Heart Association. Circulation, 141(9), e139-e596.
77. Walia, A., Gupta, A. K., Sharma, V. (2019). Role of bioac­tive compounds in human health. Acta Sci. Med. Sci, 3(9), 25-33.