Lactobacilli Combined with Microbiota-Accessible Carbohydrates in Host Health Management and Their Application in Dairy Products

Abstract

Nutrients in the gut promote the evolutionary adaptation of host microbiota, which in turn play a critical role in gut health. Dietary carbohydrate deficiencies result in the loss of some commensal lactobacilli; however, the addition of microbiota-accessible carbohydrates (MACs) promotes the proliferation of commensal lactobacilli and improves gut health. MACs are a group of substances that are not absorbed from the digestive tract and enter the gut directly for use by microorganisms and are mainly dietary components or substances secreted by the host or microorganisms. Their mechanism of action is mainly to act as growth factors for probiotics, promote changes in the intestinal environment, and regulate the balance of gut microbiota. In addition, lactobacilli combined with MACs have a wide range of applications due to their ability to enhance the unique physiological properties, balance nutritional value, and improve the taste of fermented dairy products.

1. Introduction

The gut is a complicated environment enriched with nutrient metabolism, where the microbiota grows in a nutrient-dependent manner and plays a crucial role in host health. Studies have shown that the structure of the gut microbiota changes dynamically with dietary and environmental changes, which is closely related to a number of diseases in the human body [1].

Microbiota-accessible carbohydrates (MACs) are a category of carbohydrates metabolically fermented by intestinal microorganisms and are mainly dietary components that are not directly digested and absorbed by the host or maybe secreted by the host or microorganisms in the intestinal tract (Figure 1) [2, 3, 4]. These carbohydrates are functional components that maintain the complex microbial ecosystem of the gastrointestinal tract and contribute to the prevention of intestinal ecological dysbiosis. Carbohydrates are easier to digest and convert into energy than other macronutrients, making them the primary source of energy for humans [5].

Figure 1.

General classification of MACs.

Sugars are the predominant carbohydrates, mainly including monosaccharides, disaccharides, oligosaccharides, and polysaccharides [3]. Monosaccharides are composed of a single sugar molecule, usually found in fruits, which are absorbed by the body within a few minutes of ingestion and serve as an immediate source of energy. The most common monosaccharides are glucose and fructose. Disaccharides are composed of two sugar molecules that are usually hydrolyzed by enzymes present in the small intestine, but if not digested and absorbed in the small intestine, they reach the large intestine to be broken down by intestinal microorganisms; common disaccharides are sucrose and lactose [6]. Polysaccharides are more complex structural MACs, usually composed of multiple monosaccharides linked by various glycosidic linkages.

Functional oligosaccharides are typical MACs that cannot be digested and absorbed by the human body; they can directly reach the colon and selectively stimulate the growth of beneficial bacteria (Bifidobacterium, Lactobacillus, etc.) to improve the health of the organism [7]. It is composed of 2–10 monosaccharides that are polymerized by one or more glycosidic linkages [8]; most oligosaccharides are derived from plants and algae. Common functional oligosaccharides can be used as prebiotics, mainly including arabinoxylo-oligosaccharides, fructooligosaccharides (FOS), galactooligosaccharides (GOS), and human milk oligosaccharides (HMOs), all of which contain a special glycosidic linkage structure, that cannot be hydrolyzed by ordinary digestive enzymes, as shown in Table 1 [9, 10]. Functional oligosaccharides have been widely recognized as important determinants of health and lifestyle-related diseases for a long time, and most functional oligosaccharides have been extensively researched and commercialized with abundant content in plants. Based on the metabolic properties and functional characteristics of functional oligosaccharides, isomaltooligosaccharides, fructooligosaccharides, fucosylated oligosaccharides, and sialylated oligosaccharides have been successfully applied to the development of infant milk powders and foods, thus promoting the proliferation of Bifidobacterium and other probiotics. Clinical studies have found that breast milk or infant formula with galactooligosaccharides can increase the abundance of Bifidobacterium and Lactobacillus indigenous to the infant’s intestinal tract and reduce the intestinal pH and the level of Escherichia coli, whereas milk formula without galactooligosaccharides does not have this function [11].

Type of oligosaccharides	Glycosidic bond	Monosaccharides	Degree of polymerization (DP)
Arabinoxylo-oligosaccharides	α-(1 → 2), α-(1 → 3), and β-(1 → 4)	Xylose and arabinose	5–10
Fructooligosaccharides	β-(1 → 2)	Fructose and glucose	2–9
Lactulose	β-(1 → 4)	Fructose and galactose	2
Galactooligosaccharides	β-(1 → 3), β-(1 → 4), and β-(1 → 6)	Galactose and glucose	2–8
Arabino-oligosaccharides	α-(1 → 5)	Arabinose	2–8
Isomaltooligosaccharides	α-(1 → 6)	Glucose	2–5
Soya-oligosaccharides	α-(1 → 6)	Fructose, galactose, and glucose	2–4
Human milk oligosaccharides	β-(1 → 3), β-(1 → 4), and β-(1 → 6)	Glucose, galactose, N-acetylglucosamine, fucose, and sialic acid	2–8
Gluco-oligosaccharides	α-(1 → 2), β-(1 → 3), and β-(1 → 6)	Glucose	2–10
Gentio-oligosaccharides	β-(1 → 6)	Glucose	2–10
Lactosucrose	β-(1,4)	Galactose, glucose, and fructose	2–3
Mannanoligosaccharides	β-(1,4)	Mannose and glucose	2–6
Raffinose	α-(1 → 6), α-(1 → 2)	Galactose, glucose, and fructose	3
Stachyose	α-(1 → 6), α-(1 → 2)	Galactose, glucose, and fructose	4
Isomaltulose	α-(1 → 6)	Glucose and fructose	2

Table 1.

The main functional oligosaccharides used commercially [9, 10].

2. MACs and the host gut microbiota

The human gut microbiota or human gut microbiome has approximately 150 times more genes than the entire human genome and contains approximately 10¹⁴ microorganisms of different species [12]. Among all the microorganisms found in the human gut, bacteria are the most extensively studied area. Studies have shown that the presence of certain bacterial phylum, family, genus, and species is associated with a reduced or increased risk of certain diseases and overall health conditions [13, 14, 15].

The diversity of the gut microbiota and its balance is essential for the maintenance of human health. The human intestinal tract is composed of four main phyla, namely, Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria [16]. The ratio of Bacteroidetes to Firmicutes has been reported to be 1:1 in Western populations [17]. Bacteroidetes are the major carbohydrate-degrading bacteria in the intestine and contribute to the degradation of complex pectins as they have more than 81% of the signal sequence of glycoside hydrolases and pectin cleavage enzymes compared to the Firmicutes [18]. The composition of the human gut microbiota is influenced by a variety of external factors such as age, geography, nutrition, antibiotics, probiotics, and dietary habits [19]. Among these factors, diet, especially the carbohydrates contained within it, appears to have a significant effect on the regulation of the gut microbiota [20].

MACs, as microbiota regulators with unique properties, can maintain host homeostasis and largely determine the composition and function of the gut microbiota [21]. There is a correlation between the intake of different MACs and the proliferation of different microbes. For example, fructooligosaccharides, polydextrose, and galactooligosaccharides have been associated with the proliferation of intestinal Bifidobacterium and Lactobacillus. In addition, resistant starch is associated with the proliferation of Ruminococcus, Eubacterium rectale, and Roseburia [22]. The effects of MAC on the gut microbiota and host physiology vary with the type of MAC due to differences in the ability of intestinal bacteria to utilize different MACs as food sources.

MACs serve as selective agents that can alter the composition of the microbiota, which also determines the functional and metabolic performance of the microbiota [2]. It is the main source of energy for colonic bacteria and contributes to the proliferation of beneficial bacteria [23]. MACs are also a resource for regulating the ratio of gut microbiota and can be used for the production of metabolites, such as SCFAs [24]. SCFAs are produced by MAC fermentation in the colon and mediate multiple pathways, including immune and endocrine effects, and microbe-gut-brain axis connections [25, 26]. The main mechanism of MACs is thought to be the enrichment of lactic acid bacteria, which in turn increases SCFA production, enhances the expression of tight junction proteins, and regulates the gut microbiota (Figure 2) [27]. These mechanisms are critically dependent on the individual host microbiota and persist as long as carbohydrates are consumed [28]. Current data suggest that changes in microbiota composition and diversity induced by dietary MACs are associated with host health. Although the underlying mechanism of the association between microbiota diversity and health is unclear, SCFAs are likely to be mediators of this association.

Figure 2.

MACs (e.g., dietary fiber) and host gut microbiota metabolism.

2.1 Host intestinal metabolite SCFAs

The major metabolites of MACs fermented in the colon are SCFAs, fatty acids with carbon chain lengths between one and six carbon atoms. Approximately 500–600 mmol of SCFAs are produced daily in the gut, depending on the amount of dietary fiber [4]. Acetic, propionic, and butyric acids are the most abundant SCFAs produced in the lumen of the large intestine, accounting for approximately 95% of the total SCFA production [29]. Other SCFAs, such as formic, caproic, and valeric acids, are produced at lower rates [30]. Generally, the ratio of acetic, propionic, and butyric acids in the colon is 6:2:2, respectively [31]. Fiber fermented to SCFAs in the colon lowers the pH and promotes the growth and diversity of the gut microbiota [25]. The SCFA profile in the human intestine is shaped by microorganisms, and the production of propionate and acetate in the intestine is associated with the presence of Bacteroidetes, while butyrate is mainly produced by Firmicutes [32].

SCFAs are absorbed by host cells and used as a source of cellular energy for the production of glucose and lipids. Among them, SCFAs are utilized for the citric acid cycle and mitochondrial β-oxidation after absorption by colonic cells [33]. Furthermore, SCFAs can affect host insulin sensitivity and appetite regulation by acting as substrates for gluconeogenesis and cholesterol synthesis, thus helping to prevent diet-related insulin resistance and obesity [31].

Among SCFAs, butyrate has received much attention as the preferred energy source for colonocytes [34]. Most SCFAs are absorbed via the intestinal barrier and subsequently metabolized by various tissues [35]. SCFAs perform important roles in a variety of cellular mechanisms such as chemotaxis, differentiation, proliferation, and apoptosis. They are also involved in the regulation of many pathways such as the activation of G protein-coupled receptors (GPCRs) and the stimulation and inhibition of histone deacetylases [36]. The SCFAs produced in the colon are detectable by G protein-coupled receptors present on the surface of colon cells, liver, and skeletal muscle cells, which activate G protein receptors (GPR41, GPR43, and GPR109a) [37]. Among these, GPR43 induces gastrointestinal L cells to secrete the gut hormone Peptide YY (PYY), which increases during food intake, and glucagon-like peptide-1 (GLP-1), which acts as a potent antihyperglycemic hormone that induces pancreatic β-cells to release insulin in response to elevated glucose levels [38].

3. Functional oligosaccharides and gut health

The health efficacy of functional oligosaccharides, such as naturally occurring MACs, is a research hotspot in the scientific and technological community. As reported in the literature, most of the functional oligosaccharides have probiotic functions such as regulating the intestinal immune system [39], preventing chronic intestinal inflammation [40], and relieving constipation [41] and irritable bowel syndrome. Due to their unique prebiotic properties, certain oligosaccharides have been widely used in conventional foods and infant foods, effectively improving food quality and functionality.

3.1 Enrichment of intestinal probiotics and removal of intestinal pathogens

Since intestinal microorganisms contain genes encoding functional oligosaccharide degrading enzymes, they can produce the corresponding degrading enzymes. Functional oligosaccharides can be degraded by these enzymes after passing through the gastrointestinal digestive system for fermentation by intestinal microorganisms. Studies have shown that intestinal commensal Bifidobacterium and Lactobacillus commonly possess a variety of enzymes related to carbohydrate metabolism, thus utilizing oligosaccharides as proliferation factors, which in turn regulate the gut microbiota and promote intestinal health [39]. For instance, in vitro fecal fermentation of xylo-oligosaccharides successfully enriched Bifidobacterium longum [42], and children aged 3–6 years supplemented with 6 g of FOS daily for 24 weeks showed a significant increase in the abundance of Bifidobacterium and Lactobacillus in feces [43].

Functional oligosaccharides can inhibit intestinal pathogens directly or indirectly during the process of intestinal fermentation to promote the proliferation of specific probiotics, preventing their adhesion and colonization to cause intestinal infections [27]. The direct inhibition way is that the functional oligosaccharide can bind with phytohemagglutinin on the surface of pathogenic bacteria, causing the pathogenic bacteria to lose the ability to recognize and adhere to the intestinal wall so that they will be excreted; the indirect inhibition way is that functional oligosaccharide can inhibit the overpopulation of the intestinal pathogenic bacteria by stimulating the growth of the beneficial bacteria, such as Bifidobacterium, thus maintaining the balance of the gut microbiota. For example, Bifidobacterium, Lactobacillus, and others ferment oligosaccharides to produce some organic acids, which can reduce the pH in the intestinal lumen and alter the living environment of pathogenic bacteria. In addition, Bifidobacterium can also produce lectins that bind to glycoprotein receptors in the intestinal mucosal epithelial cells and form biofilm barriers with other anaerobic bacteria in the intestinal tract to prevent the invasion of pathogenic microorganisms, producing antimicrobial peptides to eliminate certain pathogenic bacteria [44]. Lee et al. [45] found that β-GOS specifically promotes the proliferation of lactic acid bacteria and increases the production of Streptococcus lactis peptide Z, thereby inhibiting the growth of pathogenic bacteria; Lane et al. [46] showed that Manuka honey oligosaccharides significantly reduced the adhesion of E. coli O157:H7, Staphylococcus aureus, and Pseudomonas aeruginosa to HT-29 cells.

3.2 Regulation of SCFAs synthesis and promotion of nutrients intake

Anaerobic bacteria metabolize MACs by activating key enzymes via functional oligosaccharides to produce SCFAs (including acetic, propionic, and butyric acids), which are highly concentrated in the proximal part of the cecum and colon and play important roles in regulating cell proliferation, host metabolism, and the immune system [47]. Studies have shown that most SCFAs are absorbed by colonic epithelial cells and metabolized by cells in various tissues, including the colon, with only 5% of SCFAs are excreted in the feces [48]. Butyric acid, which is the main source of energy for colon cells, promotes the proliferation of intestinal epithelial cells while decreasing the intestinal barrier permeability by inducing mucin production [49]. In addition to providing energy for colonic cells, SCFAs also lead to an increase in intestinal acidity, which inhibits the growth of pathogenic bacteria and facilitates the absorption of NH₄⁺ by bacterial clusters and their excretion in the feces [50]. Therefore, it can be seen that functional oligosaccharides can exert probiotic effects by regulating the metabolism of the gut microbiota and the content of SCFAs in the intestine.

Functional oligosaccharides can produce nutrients such as proteins, vitamins B and K, as well as minerals after selective metabolism by microorganisms in the gut for further absorption and utilization by other microorganisms in the gut [51]. In addition, SCFAs produced by the fermentation of functional oligosaccharides acidify the intestinal lumen environment, which further enhances the dissolution and absorption of minerals in the colon. For example, Weaver et al. [52] found that the addition of 8% GOS to the diet of Sprague Dawley (SD) rats for 8 weeks significantly increased the abundance of intestinal Bifidobacterium and promoted the absorption of calcium and magnesium. Porwal et al. [53] showed that FOS promoted new bone formation and prevented estrogen deficiency-induced bone loss in rats by increasing butyrate cycle levels.

3.3 Maintenance of intestinal barrier integrity and improvement of the intestinal immune system

The intestinal barrier is a vital defense for human nutrient absorption, metabolism, and prevention of pathogen invasion, composed of gut microbiota, intestinal mucosal epithelium, mucus layer, immune cells, and so on [54]. Gut microbiota and diet are essential for maintaining the normal structure of intestinal mucus [55], SCFAs produced by the fermentation of intestinal probiotics with functional oligosaccharides can stimulate mucus secretion and antimicrobial peptide production, thus strengthening the intestinal barrier (Figure 3). It has been shown that HMOs in breast milk have more diverse structures and glycosylation patterns, and they maintain intestinal structural integrity by indirectly inducing mucus production, stimulating antimicrobial peptide secretion from cuprocytes, and regulating intestinal barrier maturation at multiple levels [56]. Studies have found that high doses of inulin (20%) can prevent the invasion of pathogenic bacteria, improve the permeability of the mucus layer, reduce metabolism-related parameters in obese mice, and alleviate mild inflammation, thereby promoting intestinal health [57]. Therefore, increased intake of functional oligosaccharides in the diet may lead to an increase in intestinal SCFAs and better maintenance of intestinal health.

Figure 3.

Functional oligosaccharides enhance the intestinal barrier.

The intestinal immune system is critical for preventing the invasion of pathogenic bacteria, maintaining intestinal health, and strengthening the body’s immunity. Functional oligosaccharides can enhance intestinal immunity via Bifidobacterium by the following mechanisms: (1) Bifidobacterium cells, cell wall components (intact peptidoglycan), and extracellular secretions enhance immune cell activity and contribute to the production of intestinal plasma cells and a variety of cytotoxic effectors; (2) Bifidobacterium increases the killing of NK cells and phagocytic activity of macrophages; and (3) Bifidobacterium along with its commensal bacteria produce metabolites, including SCFAs, vitamins, and others, to enhance the structural immunity of the intestinal epithelial barrier. Moreover, oligosaccharides can also regulate the function of mucosal dendritic cells through Toll receptors to exert the effect of regulating immunity. Ji et al. [58] demonstrated that butyrate, a metabolite of oligosaccharides, attenuated intestinal inflammation in DSS-induced colitis mice and significantly increased the expression of the colonic M2 macrophage-associated protein Arg1. Ma et al. [59] showed that soybean oligosaccharides treatment of healthy mice significantly increased the abundance of Bifidobacterium and Lactobacillus in the feces with an increased percentage of T-lymphocytes, NK-cell activity, phagocytosis activity, cytokine production, and immunoglobulin levels.

4. Lactobacilli and MACs improve host organism health

Lactobacilli are an extremely important physiological flora in the human intestinal tract, taking on a variety of important physiological functions of the body, with the maintenance of the microecological balance of the human body. Then, they can regulate the normal gut microbiota, maintain microecological balance, improve food digestibility and biological value, reduce serum cholesterol, control endotoxins, inhibit the growth and proliferation of intestinal putrefactive bacteria and the production of putrefactive products, produce nutrients, and stimulate the development of tissues. Thereby, they contribute to the nutritional status, physiological functions, cellular infections, drug effects, toxic reactions, immune responses, tumorigenesis, the aging process, and sudden stress responses, which are closely related to the health of the organism. Lactobacilli could metabolize MACs in vivo to promote their own proliferation; for example, GOS improves the bioactivity of Lactiplantibacillus plantarum ZDY2013 and promotes its colonization in the host [10]. In addition, numerous studies have shown that the effect of lactobacilli in combination with MACs tends to be superior to the use of either lactobacilli or MACs alone.

4.1 Lactobacilli and MACs alleviate inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic, life-threatening inflammatory gastrointestinal disease that is influenced by the host’s genetic, immune, dietary, and other factors [60]. It can cause weight loss, diarrhea, abdominal pain, fecal occult blood, and other pathological features by altering the levels of inflammatory cytokines, disrupting the intestinal barrier, generating oxygen radicals, etc. [61]

Lactobacilli play a synergistic effect with MACs, largely associated with the production of SCFAs and the modulating effect of the gut microbiota; the possible mechanisms are as follows: (1) restoration of intestinal epithelial barrier function and prevention of bacterial translocation through upregulation of mucus secretion and induction of host immunomodulatory activity; (2) regulation of gut microbiota, reduction of harmful bacteria such as Clostridium and Enterobacteriaceae, and increase of beneficial bacteria such as Lactobacillus and Bifidobacterium; (3) reduction of inflammation-related cytokine expression by inhibiting the activation of inflammatory pathways; (4) enhancement of the antioxidant capacity of the body and alleviation of oxidative damage to the body [62]; and (5) fermentation products such as lactic acid and SCFAs mediate intestinal health. In conclusion, lactobacilli in combination with MACs is an effective way of innovative IBD treatment.

4.2 Lactobacilli and MACs alleviate obesity and type 2 diabetes mellitus

Obesity is a chronic metabolic disease characterized by excessive fat accumulation in the body and is usually considered obese when the body mass index exceeds 30 kg/m². Type 2 diabetes mellitus (T2DM) is an endocrine metabolic disease characterized by elevated blood glucose levels due to insulin resistance or insufficient insulin secretion; its main symptoms are polyphagia, polydipsia, polyuria, and weight loss [63, 64, 65].

Further research on gut microbiota has shown that the ratio of Firmicutes to Bacteroidetes is positively correlated with the severity of metabolic diseases such as obesity and T2DM [66]. Canfora et al. [67] found that patients with both obesity and T2DM had dysbiosis, inflammation, and disruption of the intestinal barrier. Therefore, gut microbiota homeostasis is significant in controlling metabolic diseases such as obesity and T2DM. An earlier study found that diabetic hemodialysis patients receiving a combination of Lactobacillus acidophilus, Lacticaseibacillus casei, and Bifidobacterium for 12 weeks had significant improvements in glycemic homeostasis and plasma antioxidant capacity compared to placebo controls [68]. In addition, in a randomized, double-blind, placebo-controlled trial, 26 outpatients with glycated hemoglobin (HbAlc-1) 7.0–10.0% and total triglycerides (TG) 400 mg/dL were treated with 8 weeks of continuous XOS supplementation. XOS (4 g/day) for 8 weeks reduced not only blood glucose and glycosylated hemoglobin concentrations but also total cholesterol (TC) and low-density lipoprotein (LDL) levels [69]. Other studies have shown that L-arabinose and sucrose are two MACs that influence diet-related obesity and gut microbiota metabolism, which together act on certain bacteria, such as Bacteroidetes, to synergistically increase the concentrations of acetate and propionate in the gut, thereby preventing diet-related obesity [21]. Therefore, dietary supplementation with lactobacilli and MACs maybe a safe dietary strategy for modulating the gut microbiota environment and improving blood glucose levels in diabetic patients.

4.3 Lactobacilli and MACs inhibit pathogenic bacterial infections

Infection with pathogenic bacteria is the main type that causes an imbalance in the gut microbiota of the organism, and the symptoms of the disease are manifested in the form of diarrhea. When the host is healthy, the gut microbiota and the environment are relatively stable, and there is colonization resistance to pathogenic bacteria; however, under the influence of factors such as changes in the external environment, the composition of the gut microbiota is disturbed, and the conditionally pathogenic bacteria will become the dominant flora [70]. Antibiotics are effective means of rapidly reducing morbidity and mortality from pathogenic bacterial infections. However, the short-term use of antibiotics can cause long-term gut microbiota disruption, promote drug allergies (especially affecting infants and young children), and even lead to bacterial resistance, triggering more serious consequences such as the destruction of immune defenses and the reduction of the body’s resistance to colonization by invading pathogenic bacteria [71]. Lactobacilli are critical for the prevention of intestinal pathogenic bacterial infections and gut microbiota disorders, which prevent pathogenic bacteria from long-term colonization and growth in the host. The main mechanisms include (1) occupying ecological niche for intestinal colonization; (2) competing for nutrients needed for metabolism in the gut; (3) secreting organic acids, bacteriocins, or peptide metabolites that inhibit the growth of pathogenic bacteria; and (4) inducing immune response, removing pathogenic bacteria and their toxins, and so on.

Numerous studies have shown that exogenous supplementation with lactobacilli and MACs can effectively inhibit pathogenic bacterial infections. For example, short-term intake of L. plantarum ZDY2013 fermented milk alleviates gut microbiota disorders and intestinal inflammation caused by Bacillus cereus [72], and administration of GOS to mice enriches Lactobacillus abundance in the gut and thus fights Salmonella infection [73]. It is evident that lactobacilli and MACs can be used as new alternatives to antibiotics in the treatment of pathogenic bacterial infections.

4.4 Lactobacilli and MACs ameliorate neurodegenerative diseases

The human gut microbiome can significantly influence central nervous system activity in a number of ways, including physiological effects of the microbiota, changes in the function of the intestinal barrier, and changes in peripheral neuronal activity. The gut-brain axis controls immune activity, which is thought to be an important component of neurodegenerative diseases [26]. Studies of the gut-brain axis have shown that gut microbiota plays an important role in coordinating brain development and behavior, and the metabolites mediated by gut microbiota are the main regulators of these interactions [74]. Studies have shown that lactobacilli and their fermented products may have the potential to ameliorate neurodegenerative diseases due to their role in regulating the balance of gut microbiota. For example, L. plantarum PS128 ameliorated motor deficits and protected nerves in mice with Parkinson’s disease by modulating gut microbiota and levels of microRNAs [75]; Latilactobacillus sakei 383 and B. subtilis MC31 fermented soy products are neuroprotective in cognitively deficient mice [76]. Consumption of Eucommiae cortex polysaccharides (EP) effectively inhibits intestinal dysbiosis, thereby reducing neuroinflammation and serum endotoxin. In addition, high consumption of EP reduces glutamate and quinolinic acid levels in the hippocampus and contributes to the treatment of metabolic syndrome, with these effects promoting recovery from adult behavioral deficits and neurogenesis deficits in obese diet mice [77]. In parallel, high MAC intake improved the diversity and composition of the gut microbiota, which may help prevent cognitive decline in mice fed a high-fat, low-fiber diet [78].

5. Lactobacilli and MACs in dairy products

5.1 Characteristics and main components of fermented dairy products

Fermented dairy products are obtained by fermenting milk using appropriate and harmless microorganisms. In addition to lactobacilli, fermented dairy products contain bioactive compounds as well as bacterial-derived metabolites produced during the fermentation process. Due to the particular characteristics, fermented dairy products are excellent matrices for the incorporation of ingredients and/or nutrients that allow the properties of the final product to go beyond pure nutrition, making it a true functional food [79]. The types of fermented dairy products fall into two main categories: fermented milk and cheese. The most common use of lactobacilli in dairy products is in the production of yogurt, where they are used as a fermenting agent to ferment pasteurized raw milk to obtain yogurt products. Yogurt not only has the nutritional value of raw milk alone but also increases many microelements during the fermentation process, which helps the body absorb and utilize proteins, and it is a dairy product with a special flavor.

Fermented dairy products are rich in nutrients, including the following. (1) Protein: fermented dairy products consist of high-quality proteins such as casein (α-s1, α-s2, β-casein, κ-casein) and whey proteins (β-lactoglobulin, α-lactalbumin, lactoferrin, immunoglobulins, glucose mega peptides, enzymes, and growth factors) [80]. The proteins are hydrolyzed by lactobacilli to release specific peptides, which in turn exert immunomodulatory, antibacterial, antioxidant, and anticancer activities [81]. (2) Lipids: the lipid content of yogurt may vary depending on the source of the milk and the manufacturing process, but there is no significant change in quality compared to raw milk. In addition, dairy products contain high levels of conjugated linoleic acid [81]. (3) Carbohydrates: lactose is the main carbohydrate in dairy products and produces lactic acid when fermented. It also contains oligosaccharides and polysaccharides with some specific structural types of extracellular polysaccharides depending on the fermenting strain. (4) Vitamins and minerals: fermented dairy products are rich in a variety of vitamins and minerals with high bioavailability, mainly including vitamins A, B1, B2, B6, B12, niacin, pantothenic acid, and folic acid, as well as vitamin D, calcium, phosphorus, potassium, magnesium, zinc, and potassium iodide. (5) Probiotics: Probiotics are live microorganisms when given in sufficient amounts to benefit the health of the host. Probiotics have numerous beneficial effects on the host, and evidence of clinical effectiveness varies by probiotic strain and type of indication. While most marketed probiotics are bacteria such as Lactobacillus and Bifidobacterium, there are other microorganisms such as Saccharomyces boulardii [74].

5.2 MACs improve the properties of fermented milk

Functional oligosaccharides are used in many food products and were first and most widely used in the dairy industry [75]. Functional oligosaccharides can optimize the function of infant formula, increase the nutrient content of milk powder, and improve human health, thus becoming an important nutritional fortification factor in milk powder formulas for infants, young children, and the elderly. Japan and many European countries allowed the addition of functional oligosaccharides to infant formulas at an early stage, and the type and dosage were indicated in the outer packaging. Fermented milk has become the most popular product among dairy products due to its unique physiological functions, balanced nutrition, and delicious taste. The addition of MACs (e.g., burdock polysaccharides, inulin, and functional oligosaccharides) into fermented dairy products has been recognized as an effective strategy to improve product quality, shelf-life, and functionality, mainly in terms of increasing the survival rate of Lactobacillus during storage of the product, improving the flavor of the fermented milk, and enhancing its functional properties (anti-obesity, antibacterial, antidiabetic, and alleviation of oxidative stress, etc.) [76, 82, 83, 84, 85]. It was found that FOS and GOS could significantly increase the number of viable lactobacilli in fermented milk and improve the viscosity of fermented milk. Under the storage condition of 4°C, the mass concentration of FOS in fermented milk of 1.5 g/100 mL could have a favorable effect on the quality of fermented milk, and it could protect the survival of Lactobacillus helveticus MB2-1, slow down its decline, alleviate the post-acidification of fermented milk, and increase the viscosity of the product [86]. The application of functional oligosaccharides to fermented milk also improves antioxidant activity. Madhu et al. [83] found that the addition of FOS to fermented milk promoted the growth and metabolism of L. plantarum CFR2194 and Limosilactobacillus fermentum CFR2192, enhanced the antioxidant activity of fermented milk by increasing its protein hydrolysis power, and also reached its highest total phenolics and iron-reducing capacity during low-temperature storage. In addition, lactic acid bacteria antagonize the growth of foodborne pathogens in dairy products, and Zdenkova et al. [87] found that L. plantarum CCDM336, Streptococcus thermophilus CCDM78A, and Enterococcus durabilis CCDM53 inhibited the growth of S. aureus and the transcription and expression of virulence genes in milk. In summary, functional oligosaccharides as nutritional factors applied to fermented milk synergize with probiotics to enhance dairy product quality and function.

6. Conclusion

The gut microbiota plays an important regulatory role in health and disease. Because of the interactions between nutrition and gut microbiota, dietary interventions are one of the most effective modulators of microbiota composition and function. MACs are the primary energy source for colonic bacteria, and the abundance of MACs promotes the proliferation of beneficial bacteria. The unique properties of each MAC can be used as sensitive microbiota regulators to support host homeostasis. Lactic acid bacteria metabolize MACs to produce beneficial metabolites, SCFAs, which play regulatory roles in a variety of pathways, such as intestinal homeostasis, endocrine effects, and immunomodulation, as well as mitigating a wide range of diseases and maintaining host organismal health. Therefore, the application of lactobacilli and MACs in dairy products has been favored by consumers, which has led to the rapid development of the dairy industry. With the diversification of social development, the development of specific MACs and their combined efficacy with lactobacilli to fulfill the nutritional needs of special populations and patients with certain diseases has a broad application prospect.

Acknowledgments

The work was supported by the National Natural Science Foundation of China (32101915), the Training Program for Academic and Technical Leaders of Major Disciplines in Jiangxi Province (20232BCJ23090), and the Natural Science Foundation of Jiangxi Province (20224BAB205005).

Conflict of interest

The authors declare no conflict of interest.