Dairy-Based Probiotic-Fermented Functional Foods: An Update on Their Health-Promoting Properties

Abstract

Numerous studies have shown a link between the consumption of fermented dairy foods and improved health outcomes. Since the early 2000s, especially probiotic-based fermented functional foods, have had a revival in popularity, mostly as a consequence of claims made about their health benefits. Among them, fermented dairy foods have been associated with obesity prevention and in other conditions such as chronic diarrhea, hypersensitivity, irritable bowel syndrome, Helicobacter pylori infection, lactose intolerance, and gastroenteritis which all are intimately linked with an unhealthy way of life. A malfunctioning inflammatory response may affect the intestinal epithelial barrier’s ability to function by interfering with the normal metabolic processes. In this regard, several studies have shown that fermented dairy probiotics products improve human health by stimulating the growth of good bacteria in the gut at the same time increasing the production of metabolic byproducts. The fermented functional food matrix around probiotic bacteria plays an important role in the survival of these strains by buffering and protecting them from intestinal conditions such as low pH, bile acids, and other harsh conditions. On average, cultured dairy products included higher concentrations of lactic acid bacteria, with some products having as much as 10⁹/mL or g. The focus of this review is on fermented dairy foods and associated probiotic products and their mechanisms of action, including their impact on microbiota and regulation of the immune system. First, we discussed whey and whey-based fermented products, as well as the organisms associated with them. Followed by the role of probiotics, fermented-product-mediated modulation of dendritic cells, natural killer cells, neutrophils, cytokines, immunoglobulins, and reinforcement of gut barrier functions through tight junction. In turn, providing the ample evidence that supports their benefits for gastrointestinal health and related disorders.

1. Introduction

Milk and dairy products are known to contain bioactive compounds that are needed for many biochemical and physiological processes [1]. Because of this reason, they are an important part of a healthy diet. Fermented dairy functional foods, when consumed in enough proportions as part of a balanced diet on a regular basis, provide health benefits. In addition, this functional food also provides the body with critical nutrients such as vitamins and minerals [1]. Since fermented dairy functional foods are one of the fastest-growing parts of the food industry, it is important to know what they are. In addition to providing nutrients and energy, functional foods have a positive effect on one or more specific biological functions, either by improving a particular physiological response or by lowering the risk of disease, mostly by protecting the gut epithelial layer and maintaining the balance for gut immune homeostasis [2]. The epithelial cells in the gut serve as primary barrier surfaces that separate hosts from their external environment and have a substantial influence on the formation and function of the mucosal immune system.

Dietary components have the utmost influence on the intestinal environment due to their ability to modulate the intestinal barrier and perform various biochemical processes such as antimicrobial, antihypertensive, antioxidant, and anticancer [3]. Many studies have been undertaken to investigate the role of dietary components of fermented functional foods in intestinal permeability to identify potential correlations between diet, permeability, obesity, and inflammatory bowel disease and other diseases. Additionally, fermented dairy products are ideal for delivering probiotic bacteria to the human gut and provide the optimal environment for their growth [4]. Probiotics are described as “live microorganisms that bestow a health benefit on the host when provided in sufficient doses” [5,6]. Lactic acid bacteria (LAB) such as Lactobacillus, Streptococcus, Lactococcus, Bifidobacterium, and Leuconostoc are most common probiotic bacterial strains in fermented dairy products, either as starter cultures or naturally existing components of the raw material. Fermentation preserves and enhances the viability and production of microorganisms while retaining their probiotic characteristics [7,8]. The molecular components of probiotics associated with fermented foods influence disease-regulating mechanisms either as prophylactics or therapeutically, and such foods are often known as nutraceuticals, foodiceuticals, functional foods, or medifoods [9]. Recently, extensive research has been conducted on the effect of fermented functional products on human health, including epidemiological, observational, and clinical investigations. This review focuses on the importance of dietary fermented functional foods and their role in maintaining the homeostasis of gut microbiota and the associated immune system.

2. Dairy-Based Functional Food: Its Composition and Application in Human Health

Milk is the richest source of nutrients coupled with bioactive functional characteristics which contributes to the growth and nourishment of infants. In milk, whey accounts for around 85–95 percent of milk’s volume and maintains 55% of milk nutrients. Of these, lactose (4.5–5 percent w/v), soluble proteins (0.6–0.8 percent w/v), lipids (0.4–0.5 percent w/v), and mineral salts (8–10 percent w/v of dry extract) are the most prevalent nutrients. Whey contains more than half of total milk solids, lactose, and water-soluble vitamins as well as whey protein (20% of total protein), which is rich in essential amino acids such as lysine, isoleucine, threonine, and tryptophan [10]. Beta-lactoglobulin (BLG) (58%) and alpha-lactalbumin (13%), together with trace levels of immunoglobulin, serum albumin, and protease peptone, are the predominant whey proteins. It includes a variety of anti-microbial peptides and other compounds that have a beneficial effect on a number of diseases [11,12]. Most whey salts are composed of sodium chloride and potassium chloride (>50%), and calcium salts (mainly phosphate). In addition to these, whey contains lactic (0.5% w/v) and citric acids, non-protein nitrogen molecules such as urea and uric acid, and B group vitamins.

Studies also suggested that the fermentation of whey produces protein hydrolysates that are more absorbable than complete proteins, improve gastrointestinal health, reduce allergies/intolerance-related symptoms, and have immune-boosting effects [13]. Using mass-spectrometer-based high throughput analysis, it was shown that the milk whey contains 6210 unique proteins that are engaged in a wide variety of biological activities [14]. In addition to a high number of milk proteins, it also known to contain omega-3 fatty acids, phytosterols, isoflavins, conjugated linoleic acid, minerals, and vitamins, and so has a significant impact on the creation of functional foods. In vitro and in vivo studies have observed that fermented dairy products assisted in the maintenance of normal mucosal homeostasis and provide protection against various metabolic and pathogen-mediated diseases through their anti-oxidative, anti-microbial, anti-fungal, anti-inflammatory, anti-diabetic, and anti-atherosclerotic properties (

Table 1. The studies demonstrating the effectiveness of fermented products containing healthy bacteria and health-promoting components against particular diseases and deficiencies.

Food Matrices	Microorganism	Health-Promoting Compounds	Disease	Reference
Kimchi	Lactobacillus plantarum (L. plantarum)	Several prebiotics and the presence of vitamins, minerals, and dietary fibers and O-linked β-N-acetylglucosamine (O-GlcNAc)	Colon cancer	[15]
Whey	L.rhamnosus MTCC 5897	Probiotic released metabolites	Ulcerative colitis	[16]
Milk	Bifdobacterium breve	Bacteria and released components	Ulcerative colitis	[17]
Milk	L. rhamnosus NCDC 17 and L. rhamnosus GG	Metabolites	STZ-induced diabetic Wistar rats in high-fat diet (T2DM)	[18]
Koumiss	L. helveticus NS8	Bacterial surface components	Gastrointestinal health	[19]
Skimmed milk	Lactococcus lactis strain NRRL B-50571	ACE 3 inhibitory peptides and GABA	Anti-hypertensive activity	[20]
Milk, yogurt	LAB and Bifidobacteria species	Folate (vitamin B9), vitamin K, riboflavin (vitamin B2)	Vitamin deficiency	[21,22]
Cashew apple juice, kimchi	5 probiotic strains (Lb. acidophilus, Lb. casei, Lb. plantarum, Lb. mesenteroides and B. longum)	Vitamin K (Phylloquinone)	Vitamin deficiency	[23,24]
Milk	L. casei DN-114 00	-	Common infectious diseases (CIDs)	[25]
Milk	L. acidophilus and L. casei	-	Alleviation of lactose intolerance	[26]
Milk	L. helveticus LH511	Bioactive components in supernatant	Barrier dysfunction	[27]
Shrikhand	L. acidophilus NCDC14	-	Gastrointestinal health	[28]
Kefir	Lactobacillus lactis subs., Leuconostoc subs., Streptococcus thermophilus, Lactobacillus subs., and yeast of kefir	-	Inflammatory bowel disease (IBD)	[29]
Milk	L. paracasei CNCM I 1518	-	Cirrhosis	[30]
Milk	L. fermentum NCDC 400 and L. rhamnosus NCDC 610	-	Obesity and other related metabolic syndromes	[31]
Milk	L. rhamnosus MTCC 5897	-	Hypercholestrolemia	[32]
Milk	L. acidophilus, L. amylovorus, L. bravis, L. bulgaricus, L. casei, L. curvatus, L. fermentum, L. gasseri, L. helveticus, L. lactis, L. paracasei, L. plantarum, L. rhamnosus, L. reuteri, L. salivarius, B. lactis, B. breve, B. bifidum, B. longum, B. infantis, Pediococcus pentosaceus, and Streptococcus thermophilus.	-	Cardiometabolic diseases (CMDs)	[33]
Yogurt, capsules	L. rhamnosus GG (ATCC 53013)	Long chain fatty acids	Acute pediatric diarrhea, antibiotic-associated diarrhea	[34]
Squacquerone cheese	L. crispatus BC4	Calcium, vitamins with antimicrobial properties	Vaginal infections	[35]
Cream cheese	L. chungangensis CAU28	Short chain fatty acid	Atopic dermatitis	[36]
Cheddar cheese	Lacticaseibacillus rhamnosus and Lc. paracasei	γ aminobutyric acid (GABA)	Gastrointestinal digestion	[37]
Milk	B. longum subsp. longum YS108R; L. paracasei PS23	Exoplysaacharide (EPS); short chain fatty acids (SCFA)	Ulcerative colitis	[38,39]
Milk	Lactobacillus spp.	Free amino acids and lactate	Bone health	[40]
Milk	L. brevis DL1-11	γ aminobutyric acid (GABA), short-chain fatty acids (SCFAs), such as butyric acid	Insomnia	[41]
Milk	L. acidophilus	Phenolic compounds, GABA 1, peptides, CLA 2, folates (vitamin B9)	Antioxidant activity related disorders	[42]

).

Fermented whey is not only a source of nutrients; it also plays a role in the regulation of several physiological activities in the body [43]. This is particularly true for the intestinal tract, which is constantly in contact with dietary antigens. Numerous health benefits linked with fermented whey or whey protein ingestion have been well documented, including decreased inflammatory gene expression, protection against diarrhea caused by DSS (sodium trimethylsilylpropanesulfonate) [44], and significant influence in gut microbiota modification. These positive benefits may also be mediated by whey protein extract, which promotes mucosal innate immunity in childhood [45].

2.1. Other Dairy-Based Fermented Products

Another important product arises from the dairy industry is yogurt. The yogurt itself is not a probiotic food, but it could have non-probiotic bacteria that grew from milk fermentation. However, it can also be made better by adding probiotic bacteria. Probiotic yogurt is a combined mixture of probiotic (L. rhamnosus GG) and prebiotic (dietary fiber), and its consumption aids in the improvement of inflammatory bowel syndrome (IBS) and the maintenance of normal fecal microflora in patients with decreased putrefactive bacteria Clostridium difficile and E. coli. Recent research found that fermented probiotic yogurt improved IBS symptoms such as constipation, stomach pain, and frequency of bowel movements within six weeks of intake [46]. Another common fermented dairy product that has the ability to assist the human digestive system is cheese. It has a higher pH, a lower titratable acidity, a greater buffering capacity, a more solid consistency, a larger fat content, increased nutritional availability, and a lower oxygen concentration than yogurt. These characteristics serve to safeguard probiotic microorganisms throughout storage and transit through the gastrointestinal system [47,48]. Kefir can be produced using dairy culture as well as koumiss. In the industrial production of kefir, dairy culture is used more often than kefir grain. In addition, koumiss and kefir are almost identical when both are made using yeast and lactic acid fermentation [49,50]. Recently, Li et al. discovered that koumiss resolves thymus and spleen atrophies, increases the number of leukocytes, lymphocytes, and CD4+/CD8+ ratio of peripheral blood lymphocytes in an immunosuppressed rat model. In addition, it was able to efficiently enhance the structure of the small intestine mucosa, indicating that koumiss might serve as a therapeutic agent with a beneficial impact on intestinal immune function in immunocompromised conditions [51]. A study by Tiss et al. (2020) showed that under kefir fermented drink, in vivo and in vitro conditions showed a decrease in intestinal and pancreatic lipase activity, leading to a reduction in total cholesterol and LDL-cholesterol, and an increase in HDL-cholesterol rates, as well as body weight loss [52] (

Table 2. The beneficial effects of probiotic-fermented products on human health showing in vivo and in vitro studies.

Formulation	Probiotic Strain	Associated Mechanism	Disorder	Model Organism	Reference
Kefir drink	Commercial kefir starter culture (Danisco®)	Fermented kefir ameliorates the colitis-induced symptoms in dose-dependent manner, relieves from disease-induced diarrhea and macroscopic damages caused in mucosal wall	Inflammatory bowel disease (IBD)	Rat	[29]
Whey drink	L. rhamnosus MTCC 5897	Increases the anti-inflammatory cytokines to ameliorate the colitis-induced inflammation, enhances the tight junctional epithelial barrier integrity in mice	Ulcerative colitis	Albino mice	[16]
Fermented milk	B. longum subsp. longum YS108R	Reduces inflammatory cytokine concentrations in serum as well as their mRNA expression levels in the colon by increasing tight junction protein and MUC2 expression	DSS-induced colitis	C57BL/6J mice	[38]
Fermented milk	L. rhamnosus MTCC: 5957 and L. rhamnosus MTCC: 5897	Reduces the high-cholesterol diet (HCD)-induced body weight, hyperlipidemia, and hepatic lipids (total cholesterol and triacylglycerol), decreases the TNF-alpha, IL-6 in the liver	Diet-induced hypercholesterolemia	Wistar rats	[32]
Fermented milk	L.paracasei PS23	Strengthened tight junction through the modification of specific cecal bacteria and upregulation of short-chain fatty acids	DSS-induced colitis	Mice	[39]
Fermented milk	L. fermentum	Bioavailability of zinc	Zinc depletion	Wistar rats	[53]
Milk; fermented milk	L. fermentum	Improvement in the hypercholesterolemic effect	Hypercholesterolemic	Wistar rats	[54]
Cream cheese	L. chungangensis CAU28	Maintains Th1 and Th2 balance as well as reduces IgE immunoglobulin associated with immune homeostasis	Atopic dermatitis	Balb/c mice	[36]
Fermented milk	L. paracasei CNCM I 1518	Decreases bacterial translocation, gut dysbiosis, and ileal oxidative damage and increases ileal β-defensin-1 expression in rats treated with CCl4	Cirrhosis	Sprague-Dawley rats	[55]
Fermented milk	Lactobacillus spp.	Improves amino acid absorption that in turn enhances postprandial MPS via Akt-independent mechanisms	Skeletal muscle protein anabolism	Sprague-Dawley rats	[40]
Yogurt and fermented milk	FMP: Lactobacillus helveticus; -Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus	Greek-style yogurt protein (YP) increased the expression of genes involved in jejunal and ileal immunity and integrity in WT mice; as well as YP also improved insulin sensitivity by 65% in LRKO mice, Lactobacillus helveticus fermented milk protein (FMP) and YP both modulate the intestinal microbiota	Cardiometabolic markers and intestinal microbiota	C57BL/6J wild-type (WT) and atherosclerotic (LRKO) male mice	[56]
Fermented milk	Lacticaseibacillus casei CRL431	Probiotic-fermented milk (PFM) had the highest percentages for CD4+ and CD4+ CD8+ cells. While IL-10, TNF-α, IFN-γ, and IL-6 concentrations decreased significantly in the PFM group that increased in mice from the milk group	Breast cancer	Female BALB/c mice	[57]
Fermented milk	Lactobacillus brevis DL1-11	Modulates the composition of the gut microbiota, such as significant increases in the relative abundances of Ruminococcus, Adlercreutzia, and Allobaculum. Moreover, these changes may be associated with significant increases in the production of SCFAs in the intestine	Insomnia	Rat	[41]

).

2.2. Positive Influence of Fermented Whey-Based Products

In addition to essential nutrients, fermented whey includes a wide range of natural bioactive chemicals such as lactalbumin, lactoferrin, lactoperoxidase, lysozyme, EGF, and TGF [58]. A milk-derived whey protein concentrate rich in TGF has been developed by the food industry to stabilize epithelial barrier function and protect the intestinal barrier from inflammatory damage in infants and children [59]. TGF-1 boosted the activity of the claudin-4 promoter and protected HT-29/B6 cells against IFN-γ-induced barrier damage in a dose-dependent manner [60]. Furthermore, fermented whey supplementation protects intestinal integrity by decreasing the production of pro-inflammatory cytokines in the intestinal tract and increasing the expression of TJ proteins such as occludin and ZO-1 in LPS-treated pigs.

The anti-inflammatory properties of goat whey were investigated in a mouse model of colitis induced by 2,4-dinitrobenzenesulfonic acid (DNBS). Goat whey alleviated intestinal inflammatory symptoms, by lowering the disease activity index, colonic weight/length, and leukocyte infiltration. Additionally, goat whey boosted the expression of mucins, occludin proteins, and suppressors of cytokine signaling [61]. Bovine WPE (whey protein extract) inhibited apoptosis in human blood neutrophils and had a dose-dependent priming impact on these cells, enhancing their adhesion, chemotaxis, phagocytosis, oxidative burst, and degranulation capacities in response to further stimulation. Not only did WPE stimulate neutrophil chemotaxis, but it also raised the surface expression of CD11b, a mediator of neutrophil adherence to endothelial cells [62].

On the other hand, the bioactive forms of proteins and growth factors found in low-heat-treated whey protein concentrate (WPC) promote cell proliferation and immune response enhancement. Lactoferrin and TGF-2 were retained at a higher concentration level in low-heat-treated WPC compared to regular WPC in in vitro conditions [63]. Glycated Whey Protein Concentrate (G-WPC) generated by a non-enzymatic Maillard process exhibited no cytotoxic effect on RAW264.7 macrophage cells but elevated the production of several cytokines (i.e., TNF-α, IL-1, and IL-6 mRNA) that were shown to promote phagocytosis [64]. Interleukin-2 receptor surface expression and interferon production may also be inhibited when modified WPC is added to T and B cell cultures [65]. The NF-kB and MAPK pathways in neutrophils treated with whey protein extract generated more IL-1Ra than IL-1 [66]. Low-heat-treated WPC from acid whey substantially boosted cytokine response and proliferation in intestinal epithelial cells (IEC) as compared to low-heat-treated sweet whey [67]. WPC’s bioactive peptides promoted innate immunity in children by largely elevating CD8+ IEL (intestinal intraepithelial lymphocytes) and NK cells (natural killer cells) in the mucosal location [43]. Goat whey inhibited the production of many proinflammatory markers such TNF-α, IL-1, and IL-6 in the colonic tissue of mice with DNBS-induced colitis, as shown by [61]. Moreover, Rusu et al. found that WPE induced a time-dependent phosphorylation of inhibitory kappa B (IκB), the inhibitor of NF-B in neutrophils, which released IkB from NF-κB and activated NF-κB, thereby activating the immune response [62].

Recent research by Gupta et al. [68] showed that the fermented probiotic L. rhamnosus MTCC 5897 whey exhibited anti-inflammatory properties against E. coli-induced inflammation in intestinal epithelial cells (Caco-2) [68]. Similarly, Kaur et al. found that L. rhamnosus MTCC 5897 fermented whey had an intriguing effect on enhancing the intestinal epithelial barrier function in ulcerative colitis rats. Additionally, it may increase the RBC and lymphocyte counts in cases of anemia, which is critical for the body’s capacity to fight against infections [16]. In pregnancy, during the third trimester, the administration of a probiotic-fermented milk containing Streptococcus thermophilus, Lactobacillus bulgaricus, Lactobacillus acidophilus LA5, and Bifidobacterium animalis subsp. lactis BB12 has been associated with a decreased risk of maternal insulin resistance. In addition, yogurt intake has been associated with immunological advantages, such as a lower level of inflammatory markers in pregnant women [69] and has been shown to alter both humoral and cellular immunity [70].

2.3. Fermented Dairy Product as a Probiotic Vehicle

Fermented dairy products provide an ideal atmosphere for delivering probiotic bacteria to the human body (Figure 1). Probiotic fermentation combines the health benefits of fermented food with the benefits of good bacteria by increasing the amount of bioactive peptides that are released [71]. Additionally, because of the presence of high levels of lactic, butyric, citric, and acetic acids found in dairy products including cream, cheese, yogurt, acidophilus-bifidus milk, koumiss, kefir, and fermented drinks, these items have long been regarded the ideal matrix for probiotic microorganisms [72]. Rezac et al. observed a wide range of fermented foods and discovered that most of them had at least 10^5–7 LAB per milliliter or gram, but that this number varied greatly depending on sampling time and location. Bacteria at quantities of up to 10⁹/mL or g were often found in cultured dairy products [8]. Understanding the distinguishing characteristics of these species is greatly aided by cutting-edge omics technologies [73]. As a result, it very important to understand the genomics and proteomics profile of lactobacillus probiotics bacteria in order to gain insight into their beneficial properties [74,75,76,77,78,79].

According to Swanson et al. [80], guidelines for the minimum viable count of each probiotic strain per gram or milliliter of probiotic products differ in terms of providing probiotic-organism-related health benefits [80]. To begin, fermented dairy products such as probiotic yogurt are often believed to contain living microorganisms because, unlike many other fermented foods, dairy products are usually not pasteurized or heated at the point of manufacture, ensuring microbial viability [81]. Additionally, bacterial growth and survival in dairy products have been extensively researched [82]. A recent study demonstrated that the culture bacteria did not decrease in quantity after frozen storage of low-fat yogurt including the probiotic strains Streptococcus thermophiles and L. acidophilus [83]. Yogurt’s composition, which includes milk proteins, fat, and lactose, among other components, has proven to be an ideal environment for microbes. Its efficiency is enhanced by its frozen state and the recommended pH of yogurt is from 5.5 to 6.5 to ensure the viability of the lactic cultures during storage. Additionally, the lowered acidity promotes client acceptance, especially among those who choose milder products [84]. Therefore, fermented dairy products are the most effective probiotic delivery system (Figure 1).

Similarly, fermented milk treated with lemon and orange fibers boosted L. acidophilus numbers and improved cold storage stability when compared to the control group [85]. Likewise, fermented dairy cheese has a great potential for introducing beneficial microorganisms into the human gut owing to its unique physicochemical properties as described earlier in the text. The valuable physiochemical qualities of cheese keep probiotic microorganisms safe while they are stored and move through the gastrointestinal system [47,86]. In this way, it is safe to report that fermentation permits the maintenance and optimization of microbial viability and production while preserving probiotic properties [87].

2.4. Health Benefits of Probiotic Functional Food

Fermented probiotics are live microbial dietary additives that provide several health advantages by assisting in the stability and maintenance of the gut microbiota’s composition and enhancing resistance to pathogen infection [15]. Probiotics are also considered as potential functional foods since they give much more health advantages than standard nutritional diets [88]. As public knowledge of the influence of nutrition on health rises, the market for probiotic functional foods increases swiftly and persistently [89,90]. Probiotics have been shown to be effective in treating a variety of diarrheal illnesses, modulating immunological function, preventing colon cancer, and alleviating other chronic gastrointestinal inflammatory disorders, as shown by a growing body of high-quality, scientific clinical research [91,92]. The potential effectiveness of probiotics is increasing the interest in determining the activities and therapeutic benefits in a wide variety of neurological diseases too [93] (Figure 2).

2.4.1. Obesity and Diabetes

Diabetes is a major public health problem worldwide. Several reports have suggested the anti-diabetic properties of probiotic food containing L. paracasei and L. rhamnosus [94]. LAB alone dramatically decreased hyperinsulinemia, hyperglycemia, and glucose intolerance, suggesting a viable preventative treatment option for metabolic syndrome. According to Alihosseini et al. [95], diabetic patients who consumed probiotic-fermented milk (kefir) had lower fasting blood glucose and HbA1C levels than those who received conventional fermented milk [95]. In other research, when administered orally to 8-week-old diabetic male rats, fermented milk containing the L. casei strain AP was as effective as the commonly used diabetes drug metformin [96]. Another study demonstrated that consumption of probiotic fermented milk containing L. rhamnosus (MTCC 5897), L. fermentum (MTCC 5898), and L. rhamnosus (MTCC 5957) had an anti-diabetic effect both individually and in combination by regulating glucose metabolism, inflammation status, and serum lipid profile in diabetic rats compared to the control group [97].

2.4.2. Lactose Intolerance

Even in nations where the majority of the population can digest lactose without issue, lactose intolerance may manifest as a medical disease. Symptoms comparable to celiac disease may develop in individuals who are lactose intolerant due to the toxicity of lactose and the damage it causes to the intestinal mucosa [98]. Considering the widespread occurrence of lactose intolerance, it is preferable that milk has as little lactose as possible [99]. Because fermented milk often has lower quantities of lactose than low fat milk, it may be tolerated by those who otherwise cannot consume lactose [100]. It has been hypothesized that lactase-containing bacteria present in fermented milk persist in the digestive tract and aid in the digestion of ingested lactose [101]. Drinking fermented milk products, especially yogurt and acidophilus, was advocated for the health of Swedish volunteers aged 18–50 [102]. When planning meals for those who are lactose intolerant, it is important to keep in mind that neither yogurt nor acidophilus milk were reported to cause any gastrointestinal distress among the responders [100]. Similarly, probiotic ingestion shortened the duration of diarrhea, reduced inflammatory responses, and fostered the growth of beneficial microbes in the digestive tract [103].

2.4.3. Allergies

Consumption of probiotic-fermented foods alleviates the symptoms of food allergies in vulnerable people. A meta-analysis evaluating the effects of supplementation with various lactobacilli combinations on atopic dermatitis in normal and allergic risk groups revealed beneficial effects [62]. Consumption of probiotics such as L. gasseri KS-13, B. bifidum G9-1, and B. longum MM-2 in placebo-controlled research showed an anti-allergic effect in young people suffering from seasonal allergies through immune response regulation [104]. Further, Liu et al. [105] demonstrated that administration of the probiotic B. infantis CGMCC313-2 inhibited allergen-induced IgE antibody secretion as well as Th2 cytokine secretion and further attenuated allergic inflammation in a mouse model of allergen-induced airway inflammation and lactoglobulin-induced food allergies [105]. Saliganti et al. found that L. rhamnosus (MTCC 5897), another probiotic, reduced ovalbumin-induced allergy reactions in weanling mice [105] (Figure 3).

2.4.4. Oxidative Stress

Bioactive peptides produced by probiotics are effective antioxidants that may reduce the effects of free radical damage. The probiotic B. animalis 01 improved anti-oxidative enzyme efficiency and reduced lipid oxidation in elderly mice by decreasing MDA, lipofuscin levels, and monoamine oxidase activity [106,107]. According to the findings of Wang et al., Bacillus amyloliquefaciens SC06 has an anti-oxidative effect on intestinal porcine epithelial cells via decreasing reactive oxygen species (ROS) and regulating the Nrf-2 and Keap-1 pathways [108]. To inhibit ascorbate auto-oxidation and the generation of amino butyric acid, Garcia et al. [69] isolated L. plantarum DM5 from fermented beverages and demonstrated its anti-oxidative activity by decreasing hydroxyl radicals [69]. Another study reported that consuming fermented goats’ milk over the course of 21 days boosted overall antioxidative activity, reduced peroxidized lipoproteins, oxidized LDL, 8-isoprostanes, and the glutathione redox ratio, and improved anti-atherogenicity in healthy human individuals [109].

2.4.5. Skin Repair

Probiotic L. paracasei NCC 2461 supplementation reduced skin irritation and enhanced skin barrier function in female groups during a two-month placebo-controlled study [110]. A recent study has shown that the cell wall components isolated from L. rhamnosus GG were shown to have immunomodulatory effects against UV radiation and to inhibit the formation of skin cancers [111]. In 2019, Khmaladze et al. [112] looked at how probiotic L. reuteri DSM and its cell lysate affected overall skin health. The researchers found that the anti-inflammatory and antibacterial characteristics of probiotic bacteria helped reduce photoaging and provided greater protection against UVR-B-mediated inflammatory pathways [112]. Additionally, oral administration of L. rhamnosus GG improved skin health by reducing water loss and preserving moisture [113].

2.4.6. Hypercholesterolemia

Cardiovascular diseases (CVDs) are the major cause of mortality worldwide and are continually growing, spreading, and becoming more frequent around the globe. By 2030, the WHO predicts that CVDs would account for up to 40% of all fatalities, impacting roughly 23.6 million people worldwide. Indeed, people with hypercholesterolemia have a threefold increased risk of heart attack compared to those with normal blood lipid levels [114]. To prevent hypercholesterolemia, there has been significant interest in dietary and pharmacological interventions that block cholesterol absorption [115]. Dairy-fermented products with LAB are expected to reduce circulating cholesterol levels, hence lessening the population’s risk of cardiovascular disease. These microbes must be bile resistant and capable of deconjugating and binding bile acids and cholesterol. If these parameters are satisfied, fermented dairy products may be beneficial for lowering elevated cholesterol levels and avoiding CVDs [116].

2.4.7. Gastrointestinal Disorders

Probiotic strains for treating inflammatory bowel illness are Lactobacillus, Bifidobacterium, and designer probiotics are most commonly used in supplemented fermented foods [117]. Probiotics promote gut health by restoring a healthy balance to the intestinal flora and decreasing the probability of colonization by pathogenic microorganisms [118]. Likewise, Dore et al. investigated the effect of administering a specific dose of L. acidophilus affected ulcerative colitis symptoms in colitis mice by altering the microbiota composition in the distal colon [119]. In functional dyspepsia patients, fermented milk containing the probiotic Bifidobacterium bifidum YIT 10347 improves stomach and lower abdominal symptoms associated with the formation of gastro-protective mucin [120]. According to Eales et al., frequent use of probiotic food with the specific B. lactis DN-173 010 strain may improve gastrointestinal well-being and digestive symptoms in adult women with mild digestive illnesses [121].

3. Probiotic-Fermented Products: Stimulation and Regulation of the Immune System

Inflammation is the immune system’s response to infections, damaged cells, and toxins, among other adverse stimuli. It is a common cause of several chronic diseases, including cardiovascular disease, diabetes, rheumatoid arthritis, inflammatory bowel disease, and cancer [122]. It is essential to consume foods that possess anti-inflammatory properties. Therefore, consuming fermented probiotic foods monitors the creation of beneficial anti-inflammatory compounds. In this regard, the notable very good example is the process of fermentation of food especially by some LAB strains which potentially results in the elimination of lactose and galactose from fermented milk, hence reducing the risk of lactose intolerance and galactose buildup. At the same time, the most important aspect to note is that lactose is converted into lactic acid, which, in addition to other bioactive components, has anti-inflammatory and immunomodulatory characteristics [123].

3.1. Probiotic-Fermented-Product-Mediated Modulation of DCs

It was reported in many studies that fermented probiotics have a positive effect on intestinal epithelial cells (IECs). IECs are essential in driving the development of tolerance by suppressing DC activation, which subsequently controls the suppressive function of T regulatory cells (Tregs). IECs have also been designated to stimulate the development of CD103+ DC. This population of tolerogenic DCs induces Foxp3+ Treg cells and is dependent on TGFβ (Figure 3 and Figure 4). Under the effects of probiotics and commensal microbiota, the activated DCs induce the appropriate immune response (e.g., naïve CD4 T cells to Treg cell differentiation), which generally inhibits Th-1, Th-2, and Th17-mediated inflammatory response [124]. In vitro models based on cell lines or individual immune cells are especially appealing. These models could also be useful to quantify the development of nonspecific and specific immune responses by monitoring parameters such as cytokine and mediator production by antigen-presenting cells and biological markers for distinct cell types. Through a TLR-2 signaling route, cell-free concentrated whey from B. breve C50-fermented milk (BbC50sn) generated a unique interleukin-10 (IL-10)-rich cytokine profile and extended DC survival. The anti-apoptotic BbC50sn signal outperforms lipopolysaccharide’s pro-apoptotic action on DCs [125]. In a recent study, Jeffrey et al. showed that milk fermented with L. rhamnosus R0011 enhanced regulatory cytokine release from LPS-challenged U937 and THP-1 macrophages, while simultaneously upregulating the production of IL-1β and expression of DC-SIGN and CD206, a profile characteristic of polarization into the immunoregulatory M2 macrophage phenotype [126]. L. salivarius Ls33 stimulated the CD103+ DCs and CD4+ Foxp3+ regulatory T cells’ development in an IL-10-dependent manner [127]. Purification of peptidoglycan (PGN) from L. salivarius Ls33 demonstrated that the protective effects of L. salivarius were NOD2-dependent but MyD88-independent. Another study has identified a probiotic mixture, IRT5 (Streptococcus thermophilus, L. reuteri, B. bifidium, L. acidophilus, and L. casei), which upregulates the generation of CD4+ Foxp3+ regulatory T cells (Tregs) from the CD4+ CD25− population [128]. Overall, the data indicate that fermented probiotic factors and their bacterial components may stimulate DC maturation. In addition, evidence suggests that fermented probiotics have a specialized function in regulating intestinal DCs.

3.2. Probiotic-Fermented-Product-Mediated Modulation of NK Cells

Natural killer cells (NKs) play a crucial role in the immune response and regulation of homeostasis. They can distinguish between normal to abnormal cells with altered or missing MHC class I molecules (Figure 4). As people become older, their immune functions begin to deteriorate. It has been claimed that probiotic supplementation may reduce or reverse these age-related alterations. To confirm, a systematic meta-analysis reported that short-term probiotic supplementation (duration ranged from 3 to 12 weeks) in the elderly adults improves the cellular immune response via polymorphonuclear cell phagocytic capacity or natural killer (NK) cell tumoricidal activity [129]. Recently, another study by Gui et al. showed that probiotic Lactobacillus interventions alone or in combination with Bifidobacterium enhances the natural killer (NK) cell function in healthy elderly individuals [130]. A study conducted in Japan by Shida et al. on healthy volunteers showed that regular consumption of L. casei Shirota-fermented milks orally for three weeks resulted in the improved NK cell activity [131]. It found to be very helpful for individuals with low NK cell activity and in turn help in the overall better health and reduction in illness, as measured in peripheral blood mononuclear cells (PBMC). In a separate study, the administration of L. casei Shirota (LcS) to patients whose colonic polyps had been surgically removed has shown a significant reduction in the recurrence of colorectal cancer. The results also showed the specific mechanisms of action of LcS on positively correlated NK cell activity via induction of IL-12 and TNFα production [132].

However, ingestion of a combination of eight strains of sonicated probiotic bacteria named sAJ2 (Streptococcus thermophiles, B. longum, B. breve, B. infantis, L. acidophilus, Lactobacillus plantarum, and L. casei) by patients demonstrated improvement in the NK function both in terms of IFN-γ secretion as well as NK-cell-mediated cytotoxicity after four weeks of consumption [133]. The relevance of bacteria-mediated enhancement of immune activation and restoration of immunological function in patients is shown by the increased activity of NK cells observed in both in vitro and in vivo investigations. In addition, researchers had shown earlier, in vivo, in the humanized-BLT mouse model that the consumption of AJ2 probiotic bacteria improved NK cell activity and linked with the reduction or disappearance of oral and pancreatic cancers [134]. The primary effect of LAB on NK cells is the elevation of their cytotoxic activity and, therefore, antitumor responses, as opposed to the rise in NK cell count. In accordance with this, a number of human investigations have shown that LcS supplementation increases NK cell function, with in vivo studies revealing that this is due to IL-12 [135]. This information suggests that certain LAB initiate NK interactions effectively, which improves the cytolytic capacity of NK cells in mucosal immunity.

3.3. Probiotic-Fermented-Product-Mediated Modulation of Neutrophils

Neutrophils are crucial for innate immunity and pathogen identification and response. They are short-lived myeloid cells that readily combat infection by means of oxidative-dependent generation (ROS), also known as oxidative burst, and phagocytic clearance; both of which are assisted by neutrophil extracellular traps (NETs). Probiotic bacteria on neutrophils are likely to target its effector functions: ROS production, phagocytosis, NET formation, hydrolytic enzyme activity, chemokine-mediated recruitment, and inflammatory cytokine secretion; thus, having a profound effect on neutrophil-mediated responses associated with acute infection and chronic infection/immunopathogenesis. L. rhamnosus GG has also been demonstrated to inhibit NET formation and, as a result [136], caused decreased ROS generation and avoidance of tissue death by chronic inflammation, with the reduction of ROS production indicating an inhibitory impact on NF-κB.

Additionally, it was shown that cell-wall extract of L. gasseri ATC33323 upregulated the expression of TNF-α, IL-1β, MIP-1α, and MCP-1 in a Sprague-Dawley rat model of sepsis [137]. L. brevis enriched with selenium nanoparticles was found to be capable of reducing liver metastasis in a metastatic mouse (BALB/c) breast cancer model. The study is of relevance to neutrophils since the immune responses are in the form of elevated IFN-γ and IL-17 cytokine levels and enhancement of NK cell activity [138]. Recently, Li et al. reported that oral administration of microbial metabolite butyrate markedly ameliorated mucosal inflammation in DSS-induced murine colitis through inhibition of neutrophil-associated immune responses [139]. Further, in vitro studies confirmed that butyrate suppressed neutrophil migration and formation of NETs from both CD and UC patients. B. animalis MB5 and L. rhamnosus GG strains have been shown to suppress enterotoxigenic E. coli K88 induction of the NFκB-dependent inflammatory mediators TNFα, IL-1β, IL-8, Gro-α, and ENAP-78, resulting in a corresponding inhibition of neutrophil transmigration [140].

3.4. Probiotic-Fermented-Product-Mediated Modulation of Cytokines and Immunoglobulin

Following the ingestion of fermented milks, several LAB strains have been shown to enhance both innate and adaptive immunity in animal models. Probiotic-fermented products are being studied for their immunomodulatory properties in a number of animal and human clinical studies. The effects of LAB depend on the strain, and many lactobacilli work on payer patches to improve IgA synthesis, phagocytosis, and anti-inflammatory and anti-allergic properties by stopping the production of cytokines and immunoglobulin E (IgE) [141]. In a mouse colon cancer model, yogurt intake reduces tumor development by a reduction in inflammatory response, an increase in IL-10-secreting cells, apoptosis, and a decrease in procarcinogen enzymes [142].

Yogurt administration to DMH-injected mice causes a reduction in IgG and CD8 T cells while increasing IgA and CD4 T lymphocyte numbers in the lamina propria of the large intestine. Given that IgA is regarded as a crucial barrier in colonic neoplasia, the rise in IgA-secreting cells in the bowel of mice given yogurt but not IgG cells aid to control the inflammatory response. On the other hand, bioactive peptides in kefir cause macrophage activation, phagocytosis, and the generation of nitric oxide (NO) [143]. In healthy young women, regular consumption of fermented milk rich in probiotic and prebiotic bacteria showed favorable benefits on the skin by reducing dryness and on the intestines by encouraging bowel movements and cutting down on phenol synthesis by gut bacteria [144].

In a mouse model, animals administered Malleable Protein Matrix (MPM), a novel fermented whey protein-based product, demonstrated a substantial reduction in ear inflammation with minimal side effects when compared to mice given hydrocortisone. Blood polymorphonuclear cells and the quantity of myeloperoxidase in the ear showed that the MPM seemed to prevent neutrophil extravasation into tissue [145]. According to Cristofori et al., feeding mice B. breve for 9 days before generating DSS colitis lowers inflammation by altering the makeup of T cells in the distal colon by boosting T-reg-related cytokines and decreasing Th1-related cytokines [146]. In mice, oral treatment of the probiotic L. casei CRL 431 exhibited a protective effect by raising IFN-α, IL-6, and IL-10 production in the lamina propria of the small intestine and lowering TNF production [147]. Similarly, the fermented whey dairy beverage therapy significantly improved animal survival in the mouse model (70%) and reduced pathogen translocation to the liver (2/10). It also resulted in fewer lesions in the animal’s histology and provided inflammatory protection against Salmonella Typhimurium infection [148]. Furthermore, Nipa vinegar’s active ingredients, particularly the polyphenols, were found to enhance the anti-inflammatory, hypolipidemic, and weight loss effects in obese mice when compared to synthetic acetic acid vinegar, demonstrating that bacterially fermented Nipa vinegar has a favorable impact on inflammation and lipid metabolism [149]. Hunsche et al. investigated the immunological response in BALB/c mice fed milk fermented by L. casei DN-114001, L. delbrueckii subsp. Bulgaricus, or S. thermophilus over a period of 98 days. According to the results, oral consumption of fermented milks increased the number of intestinal samples with IgA+ TNF-α, interferon IFN-γ, interleukin IL-12, and interleukin (IL-10) generating cells. In the lamina propria of the gut, CD4+ and CD8+ cell populations were also increased [150]. However, mucosal areas outside of the gut lacked any alterations. Additionally, it has been shown that adherent cells derived from Peyer’s patches and peritoneal macrophages both produce more cytokines in vivo when exposed to kefir solids (which include bacteria) and liquid supernatant [151].

3.5. TLR-Mediated Immune Response and Probiotic-Fermented Products

Toll-like receptors contribute to IEC homeostasis by governing appropriate host responses to the intestinal microbes. LAB are capable of triggering TLR-2/TLR-6 signaling pathways, 16 different LAB strains of food and human origins were characterized and tested for their interactions with specific TLRs [152]. L. plantarum-purified DNA also modulates the immune response of host cells by interacting with TLRs, as reported by Kim, whose studies show that L. plantarum-purified DNA inhibits LPS-induced TNF-α production in THP-1 cells. Furthermore, L. plantarum-purified DNA blunt the expression of TLR4, TLR2, and TLR9, which induce NF-κB activation through the LPS signaling pathway, leading to pro-inflammatory cytokine upregulation [153]. Recently, Jia et al. showed that probiotic L. salivarius AR809 could attenuate the inflammatory response produced by S. aureus by elevating autophagic protein level and blocking the TLR-mediated NF-κB signaling network [154]. Supernatant from B. breve C50 strain culture (BbC50sn) induced maturation and activation of human DCs, but only after fermentation of a milk whey-based medium. BbC50sn induced a specific interleukin-10 (IL-10)-rich cytokine profile and prolonged DC survival via a TLR2 pathway [155]. Probiotic L. fermentum (MTCC-5898) exerts immunosuppressive effects in the presence of E. coli by inhibiting pro-inflammatory cytokines release and enhancing the expression of anti-inflammatory cytokines via TLR-2/TLR-4 and the NF-κB signaling pathways [156].

In summary, probiotics are bacteria found in fermented products that regulate immune responses by interacting with dendritic cells (DCs), monocytes/macrophages, and lymphocytes, resulting in an increase in IgA response [157]. Fermented foods rich in probiotics stimulate the production of antimicrobial peptides by host cells, including bacteriocins and beta-defensins, which serve as an infection defense. They also generate lactic acid and acetic acid, both of which have potent antibiotic effects on a range of Gram-negative bacteria. Probiotic-fermented items stop the colonization of harmful bacteria by blocking the mucosal attachment site or denying the bacteria food. This behavior is referred to as competitive exclusion. The integrity of the epithelial barrier is therefore changed by components generated from dairy-fermented probiotic bacteria, and tight junction protein synthesis is promoted by TLR regulation. Thus, the mucosal layer, antimicrobial peptide, secretory IgA, TLRs, and cytokines make up the overall intestinal barrier defense, all of which are crucial for maintaining the equilibrium of the gut’s immune system [158]. In addition, the complete nature and breadth of the probiotics and TLR signaling were both covered in the recently published review paper [159].

4. Probiotic-Fermented-Product-Mediated Reinforcement of Gut Barrier Function

Probiotic fermentation combines the health benefits of microorganisms with those of fermented foods [160]. Consuming probiotic bacteria via fermented milk is also a magnificent way to restore balance to the gut flora and preserve the epithelial barrier function [161]. By encouraging the production and assembly of tight junction proteins, probiotics and released metabolites improve barrier function. They also guard against disruption of tight junctions brought on by inflammatory stimuli. Additionally, they cause a variety of cell signaling pathways to be activated, which strengthens tight junctions and the barrier function [162].

4.1. Modulation of Tight Junctional Barrier Integrity

The paracellular gap is sealed by a circumferential belt made of tight junctions, which prevents macromolecules from diffusing across the epithelium [162]. Recently, Kaur et al. showed that L. rhamnosus fermented whey was important in maintaining barrier integrity in a mouse model of DSS-induced colitis. Prior to the induction of colitis, ingestion of whey fermented with the probiotic L. rhamnosus (PFW) substantially decreased the disease activity index and enhanced the histology scores. The considerably diminished levels of pro-inflammatory markers (IL-4, TNF-α, CRP, and MPO activity) and the enhanced levels of the anti-inflammatory cytokine TGF-β with IgA in the intestine upon feeding PFW appeared to prevent inflammation on colitis induction (Figure 2). This protection is mediated by the pathogen recognition receptors TLR-2, which result in the upregulation of tight junctional genes (ZO-1, occludin, and claudin-1) and the localized distribution of junctional (claudin, occludin, and ZO-1) and cytoskeleton (actin) proteins, thereby enhancing immune homeostasis and intestinal barrier integrity. In addition, PFW ingestion resulted in lower serum concentrations of the FITC-dextran marker, which directly confirmed the host gut’s better health [16]. In a similar manner, after consuming probiotic-fermented milk products, certain microorganisms (such as B. longum) become a permanent part of the human intestinal microbiota, while others, such as L. casei, exert their effects transiently as they pass through by remodeling or influencing the community of microbes that are already present [163].

Additionally, it was found that the broth prepared by fermentation of L. acidophilus in the presence of enhanced extracts from E. sativa seeds has a high concentration of glucoerucin and significantly decreased CXCL-8 expression in Caco-2 cells after EHEC infection, as well as epithelial disruption caused by EHEC infection [164]. L. casei BL23 and milk cooperate synergistically to protect the integrity of the epithelial barrier against pro-inflammatory cytokines [165]. Likewise, ingestion of L. plantarum Lp91 in the form of fermented dairy products may enhance the intestinal barrier’s function in both normal and enteric infection circumstances. Modulation of critical regulatory receptors TLR-2 and TLR-4, as well as upregulation of tight junction genes and secretory components mucin-2, -defensin-2, and cathalicidin, indicated the mechanism of protection against infection [166]. The L. paracasei 01 fermented milk beverage decreased macromolecule permeability and improved intestinal epithelial integrity that has been damaged by dextran sodium sulfate. Additionally, fermented milk beverages containing live L. paracasei 01 enhanced intestinal epithelial cell (Caco-2) proliferation, reduced lipopolysaccharide/tumor necrosis factor (TNF-α)/interferon (IFN-γ)-induced Caco-2 cell death, and raised the production of the chemokine CCL-20 [167].

The administration of B. longum subsp. longum YS108R fermented milk was shown to alleviate DSS-induced colitis through its anti-inflammatory properties, by protecting mucosal barrier integrity, and maintaining gut microbiota homeostasis. It also significantly decreased the expression of IL-6 and IL-17A and maintained the tight junction proteins, while increasing the expression of mucin2 [38]. Jeffrey et al. evaluated the immunomodulatory activity of culture supernatants obtained from milk fermented by various LAB (L. helveticus, L. casei ssp. Casei 31, L. casei subsp. rhamnosus 4008, L. acidophilus 41, L. delbrueckii subsp. bulgaricus 1208, and Streptococcus). Additionally, the effect of fermented milk supernatant by L. helveticus R389 regulated calcineurin expression and epithelial barrier strengthening [126]. The findings suggested that the supernatant of fermented milks improved gut mucosal immunity by bolstering the epithelium and nonspecific barriers as well as gut function at infection sites. This is an important signal in the network that activates the gut immune system [168].

4.2. Modulation of Gut Permeability

The gastrointestinal epithelium offers a structural and immunological barrier against the broad spectrum of noxious and immunogenic substances present in the gut lumen. Compromised intestinal mucosal integrity and breakdown of gastrointestinal mucosal barrier function, the condition generally referred to as “Leaky Gut Syndrome” [169]. Lactobacillus helveticus ASCC 511 (LH511)-fermented milk enriched with citrulline enhances the intestinal epithelial barrier function and inflammatory response in IPEC-J2 cells caused by pathogenic E. coli. It restored the transepithelial electrical resistance (TEER) and regulated the expression and distribution of tight junction (TJ) proteins (zonula occluden-1 (ZO-1), occludin, and claudin-1), toll-like receptors (TLRs) (TLR2 and TLR4), and negative regulators of the TLR signaling pathway (A20 and IRAK-M) [170].

Consumption of L. plantarum Lp91 in the form of fermented dairy food could increase the functioning of the intestinal barrier in normal health as well as enteric infection conditions. Protection against infection was demonstrated by the modulation of key regulatory receptors TLR-2, TLR-4 and by upregulating the expression of the tight junction genes along with secretory components, mucin-2, β-defensin-2, and maintaining gut permeability [166]. L. paracasei PS23-fermented milk (PS23 FM) and its heat-killed counterpart (HK PS23 FM) could protect or reverse the increased epithelial permeability by strengthening the epithelial barrier function in vitro by increasing transepithelial electrical resistance (TEER). In vivo analysis of the regulation of intestinal physiology demonstrated that low-dose L. paracasei PS23-fermented leads to upregulation of short-chain fatty acids which ameliorated DSS-induced colitis. This anti-colitis effect may be exerted by deactivating the inflammatory cascade and strengthening the tight junctions that cause the decrease in gut leakage [171]. Milk fermented with Lactococcus lactis ssp. cremoris JFR1 resulted in increased transepithelial electrical resistance, which remained constant for the duration of infection (up to 3 h), illustrating a protective effect on Salmonella invasion of intestinal epithelial cell cultures [172].

Moreover, L. casei BL23 and milk work synergistically to prevent damage to epithelial barrier integrity reduced losses to transepithelial electrical resistance (TEER) induced by pro-inflammatory cytokines [173]. Pretreatment of Caco-2 cell monolayers with L. plantarum significantly attenuates phorbol ester-induced redistribution of ZO-1 and occludin from the intercellular junctions and the increase in permeability. The surface layer lattice, being the cell’s outermost structure, is typically regarded to be the first bacterial component to interface directly with the intestinal epithelium. SLPs may preserve the intestinal barrier by altering F-actin distribution and modifying tight junctional proteins at the mRNA and protein levels [174]. Previous research has identified that in combination with fermented and probiotics foods, diet containing fruits, vegetables, and whole grains are essential modulators of gut microbes due to their high fiber, phenolic chemical, and prebiotic content [175]. Additionally, diets that include fermentable fibers and resistant starches promote gut fermentation and SCFA (short chain fatty acid) synthesis. Increased SCFA synthesis, in turn, would improve epithelial protection by strengthening the barrier through increased TJ protein and TEER, as well as reduced permeability and bacterial translocation [176,177]. Therefore, probiotic-fermented foods are well positioned in the market because they have strong consumer acceptability. As a result, research into this kind of product is attractive since it shows long-term promise. However, well-designed and relevant clinical trials are needed to find out more about how probiotics affect the gut-immune system.

5. Conclusions

Fermented functional foods are those that may provide extra health benefits beyond the nutrients they already contain. The classification of dairy-fermented products as functional foods represents a large potential for the dairy industry. Studies have shown that fermented dairy foods have a beneficial impact on gastrointestinal health and have the ability to improve the immune system. These benefits have been known for a long time. The frequency of gut disorders has grown in recent years due to the Western lifestyle and the eating habits linked with commercial items, which promote gut permeability and antigen transcytosis and produce inflammation, ulceration, and apoptosis. Milk is rich in LAB and bifidobacteria, which makes it an excellent environment for the growth of probiotic bacteria. This is one of the reasons why milk is used to create functional meals. The consumption of fermented dairy products has the potential to improve the health of the body in a range of diseases, including diarrhea, obesity, high cholesterol, cardiovascular health, and others. Fermentation also increases the amount of helpful bioactive peptides, vitamins, and other elements generated by bacteria, which are all beneficial to the body’s overall health. Probioactives are bioactive compounds related with the food matrix and probiotic microorganisms that are present in foods. The administration of fermented dairy foods with or without probiotic bacteria is essential for human health by preventing or treating inflammatory diseases, as proven by a range of strains, according to preclinical and clinical studies that promote health. As a result, fermented dairy foods have the potential to evolve into a “functional food package” with extended shelf life and sensory qualities for the benefit of humankind as a whole.