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Shehata, A. Probiotics, Prebiotics, and Phytogenic Substances for Gut Health. Encyclopedia. Available online: https://encyclopedia.pub/entry/19437 (accessed on 17 November 2024).
Shehata A. Probiotics, Prebiotics, and Phytogenic Substances for Gut Health. Encyclopedia. Available at: https://encyclopedia.pub/entry/19437. Accessed November 17, 2024.
Shehata, Awad. "Probiotics, Prebiotics, and Phytogenic Substances for Gut Health" Encyclopedia, https://encyclopedia.pub/entry/19437 (accessed November 17, 2024).
Shehata, A. (2022, February 15). Probiotics, Prebiotics, and Phytogenic Substances for Gut Health. In Encyclopedia. https://encyclopedia.pub/entry/19437
Shehata, Awad. "Probiotics, Prebiotics, and Phytogenic Substances for Gut Health." Encyclopedia. Web. 15 February, 2022.
Probiotics, Prebiotics, and Phytogenic Substances for Gut Health
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This entry is adapted from the peer-reviewed paper 10.3390/microorganisms10020395

The gut microbiota has been designated as a hidden metabolic ‘organ’ because of its enormous impact on host metabolism, physiology, nutrition, and immune function. The connection between the intestinal microbiota and their respective host animals is dynamic and, in general, mutually beneficial. This complicated interaction is seen as a determinant of health and disease; thus, intestinal dysbiosis is linked with several metabolic diseases. Therefore, tractable strategies targeting the regulation of intestinal microbiota can control several diseases that are closely related to inflammatory and metabolic disorders. As a result, animal health and performance are improved. One of these strategies is related to dietary supplementation with prebiotics, probiotics, and phytogenic substances. These supplements exert their effects indirectly through manipulation of gut microbiota quality and improvement in intestinal epithelial barrier. 

gut microbiota dysbiosis tight junctions synbiotics poultry feed additives

1. Introduction

The permeability of the intestinal tract controls the uptake of nutrients and the transport of unwanted extracellular substances such as bacteria and xenobiotics, in addition to the non-digested substances. Therefore, gut health plays an essential role in the pathogenesis of various intestinal disorders. The permeability of the intestine is controlled by gut microbiota, digestive secretions, physical barriers (mucin, intestinal epithelial cells lining and tight junctions), and chemicals such as cytokines [1].
Under normal conditions, the symbiotic relationship between the gut microbiota and the host crucially determines intestinal health. However, a disturbance in the gut microbiota can lead to an imbalanced host–microbe relationship, which is called “dysbiosis” [2]. Several factors, such as antinutritional factors in feed, heavy metals, toxic substances, bacterial toxins, herbicides, and antibiotics, can disrupt the gut microbiota. These impacts can lead to localized inflammation, extensive infection, or even intoxication [3][4][5], Additionally, the intestinal epithelium forms tight connections, acting as a biological barrier that controls the paracellular transit of different materials across the intestinal epithelium, including ions, solutes, and water. It also functions as a barrier of extracellular bacteria, antigens, and xenobiotics.
The impaired intestinal barrier function, commonly known as “leaky gut”, is a condition in which the small intestine lining becomes damaged, leading to infiltration of luminal contents such as bacteria and their associated components including toxins to pass between epithelial cells. These conditions subsequently lead to cell damage and/or inflammation of the intestine, characterized by increased levels of bacteria-derived endotoxins in blood. This inflammatory process consumes significant amounts of nutrients, and, subsequently, has negative effects on metabolic responses, in particular on immunometabolic and endocrine responses. As a result, animal performances are severely reduced [6].

2. Intestinal Microbiota in Poultry

Microorganisms that live in animals’ gastrointestinal tracts (GITs) are a prime example of beneficial bacteria [7]. Indeed, the GIT is the home of a diverse and plentiful microbial community providing essential functions to their host animals. Although the intestine is exposed to microflora components from birth or hatching, little is known about their impact on healthy development and function. Microorganisms are more densely populated in the GIT than in any other organ [7]. Animals have evolved the ability to host complex and dynamic consortia of microbes over their life cycle during millions of years of evolution [8].
Colonization of avian guts could already start during embryogenesis [9] and progresses to the formation of a complex and dynamic microbial society [10]. Based on principles established during animal history, extensive and combinatorial microbial–microbial and host–microbial interactions are likely to govern the microbiota assembly [11]. Comparing germ-free rodents that were raised without exposure to microorganisms to those that built up a microbiota since birth, or those that were colonized with microbiota components during or after postnatal development, a variety of host functions influenced by indigenous microbial communities were identified [12].

3. Intestinal Barrier and Tight Junctions

Enterocytes are the cornerstone of the intestinal mucosal monolayer that protects the host from the external environment. A scheme of the intestinal epithelial barrier and some interactions with intestinal microbiota is shown in Figure 1. Enterocytes are connected by the so-called tight junctions (TJs), which constitute a continuous belt of intimate contacts formed during the assembly process of integral transmembranes (occludin, claudins, junctional adhesion molecules (JAMs), and tricellulin) and peripheral membranes (zonula occludens-1 (ZO-1), ZO-2, and ZO-3). The TJ proteins are located between adjacent enterocytes, sealing the paracellular space and regulating the permeability of the intestinal barrier. Therefore, these proteins prevent the transit of microorganisms, toxins and other antigens from the intestinal lumen to the systemic circulation [13][14]. The formation and function of tight junctions are controlled by intracellular signal transduction pathways: (i) protein kinase C (PKC), A (PKA), and G (PKG) signaling, (ii) phosphatase-Rho, myosin light chain (MLC) kinase (MLCK), MAPK signaling, and (iii) the PI3K/Akt pathway [15][16].
Microorganisms 10 00395 g003
Figure 1. Intestinal epithelial barrier and intestinal microbiota interaction.

4. Biomarkers Related to Intestinal Health of Animals

The interactions between the epithelial barrier function, intestinal inflammation, and the microbial environment influence gut health [17][18]. Therefore, the discovery of reliable, widespread biomarkers to measure intestinal inflammation and barrier function is an important ongoing area of research. A summary of some of the known biomarkers related to intestinal health is presented in Table 1. To study intestinal health, it is also important to develop inflammatory gut models with different challenge conditions (anti-nutritional factors, pathogens, toxins, and environmental triggers) [19][20]. Inflammation can also be associated with oxidative stress and changes in the expression of genes related to oxidative stress, indicating that oxidative stress may have a critical role in the physiological intestinal function [21]. One quantitative technique that is used to evaluate the integrity of tight junction proteins in epithelial cell monolayers is the measurement of transepithelial electrical resistance (TEER) [22]. Mitochondrial respiration is required to maintain TEER, implying that oxidation plays a critical role in Caco-2 cell tight junction stability [23]. 
Table 1. Potential biomarkers to evaluate intestinal health.
Measurement/Function Biomarker Type
Antioxidant activity Superoxide dismutase (SOD), Thiobarbituric acid reactive substances (TBARS), Total antioxidant capacity
Gene expression of host protein
biomarkers and tight junction		 Fatty acid binding protein (FABP), Fibronectin, Occludin, Zonula
occludens, Claudins
Immune activity Acute phase proteins, Calprotectin, Lipocalin, Immunoglobulins (IgA), Interferon gamma (INF-γ)
Intestinal permeability Fluorescein isothiocyanate dextran (FITC-d), Trans epithelial electrical resistance (TEER), Bacterial translocation
Enterocyte function Extracellular signal-regulated kinase (ERK), Citrulline
Adapted from Chen et al. [20] and Baxter et al. [24].
Biomarkers for the evaluation of intestinal health can also be related to monitoring intestinal function. Citrulline is a nitrogen-containing by-product of glutamine metabolism that can be converted to arginine and is produced mainly by enterocytes of the small intestine [25]. Plasma citrulline levels have been associated with intestinal absorption of markers such as mannitol in pre-weaned piglets, indicating that citrulline may be utilized to monitor intestinal function [26]. The extracellular signal-regulated kinase (ERK) is another biomarker that can be considered to be an option because it serves as a critical signaling pathway for intestinal epithelial proliferation and tissue healing. Thus, serum ERK activity can reflect intestinal disruption caused by a stressor [27].

5. Probiotics

Properly dosed probiotics improve gut microbial balance, colonization resistance against infections, and immunological responses [28]. Lactobacillus spp., Streptococcus thermophilus, Enterococcus faecalis, and Bifidobacterium spp. are the most frequent lactic acid bacteria (LAB) utilized in probiotic formulations. Possible mechanisms of action include: (i) maintaining a healthy balance of bacteria in the gut by competitive exclusion, i.e., in a process by which beneficial bacteria exclude potential pathogenic bacteria via competition for attachment sites in the intestine and nutrients, and (ii) preventing bacterial overgrowth in the gut [29].
There is also ample evidence that probiotics affect the immune system by balancing pro- and anti-inflammatory cytokines [30]. Some probiotics have antioxidant capabilities and improve barrier integrity [31]. Another study found that both innate and humoral immunity are improved while using probiotics [32]. 

6. Prebiotics

Prebiotics are a relatively recent concept, arising from the idea that nondigestible food elements (e.g., nondigestible oligosaccharides) are selectively fermented by bacteria known to benefit gut function [28]. The proliferation of endogenous lactic acid bacteria and Bifidobacteria in the gut has been demonstrated to benefit host health [33]. Prebiotics may help Bifidobacteria and lactobacilli to proliferate in the gut, enhancing the host microbial balance. Prebiotics, unlike probiotics, encourage the gut bacteria that have acclimated to the gastrointestinal tract’s environment [34]. Other gastrointestinal alterations include increased intestine length in elderly humans [35]. Prebiotics alter the colonic microbiota and may impact gut metabolism in humans [36]. Healthy gut microbiota may increase absorption, protein metabolism, energy metabolism, fiber digestion, and gut maturation in Leptin-Resistant Mice [37]. Prebiotics have also been shown to improve host defense and reduce pathogen-induced mortality in birds [38].
Prebiotics’ ability to increase the quantity of LAB in the gut may aid in the competitive exclusion of pathogens from the gastrointestinal tract of birds [33]. The increased intestinal acidity caused by prebiotics may also help to reduce infections in the gut of chickens. Prebiotics have also been shown to boost the immunological response in chickens, resulting in faster infection clearance [39].

7. Synbiotics

When used in combination with prebiotics, probiotics are termed synbiotics, and have the ability to further improve the viability of the probiotics. Probiotics, prebiotics, and synbiotics are now widely used globally. 

7.1. Role of Synbiotics in Poultry Production

Immediately after hatching, birds must switch from endogenous yolk energy to an exogenous carbohydrate-rich diet [40]. During this vital period, intestine size and morphology change dramatically. Changes in epithelial cell membranes alter the mechanical interface between the host’s internal environment and the luminal contents. Studies on early growth nutrition and metabolism in chicks may help optimize nutritional management for optimum growth. The end products digested by symbiotic gut microorganisms can modify not only gut dynamics, but also various physiologic systems [41]. The multiple roles of synbiotics on digestive physiology are summarized in Figure 2.
Microorganisms 10 00395 g004
Figure 2. The role of synbiotics on digestive physiology.

7.2. The Role of Short Chain Fatty Acids (SCFAs) on Digestive Physiology

The principal fermentative response in humans and chickens is the hydrolysis of non-digestible polysaccharides, oligosaccharides, and disaccharides to simple sugars, which are then further fermented by gut bacteria, for example, into SCFAs. In the large intestine, carbohydrate presence and fermentation can change gut physiology. As the intestinal microbiota are established, the SCFA concentration rises from undetectable levels in the ceca of day-old chicks to the greatest concentration at day 15 [42]. The effects of SCFAs are separated into those in the lumen and those in the big gut wall cells. SCFAs are major luminal anions.

8. Phytogenic Feed Additives

Phytogenic feed additives (PFAs) are classified as sensory and flavoring compounds according to the European Union Legislation (EC 1831/2003) [43]. It has been suggested that PFAs increase the growth performance [44][45], nutrient digestibility [46], and gut health [44][47][48] in poultry. Currently, PFAs are used in feeding programs of poultry and swine. The count of Lactobacillus spp. in the caecum was increased when 75 mg/kg red ginseng root powder was added as a feed supplement [49]. 
Several factors can modulate the intestinal microbiota causing either a positive or negative effect on the host [50]. Dietary effects on the composition of microbiome are shown in Table 2. Supplementation of day-old chickens with antibiotics negatively modulated the intestinal microbiota and adversely affected the immune system development [51].
Table 2. Dietary effect on the composition of the microbiome.
Enterotypes Biological Activities Favorable Substance/s
Bacteroides
  • saccharolytic, proteolytic
  • biotin, riboflavin, pantothenate and ascorbate synthesis
 proteins and fats
Prevotella
  • mucin/glycoprotein degrading
  • thiamine and folate synthesis [2].
 high fiber diet
Ruminococcus
  • mucin/glycoprotein degrading.
  • transmembrane transport of sugars
 Sugars
Adapted after [52][53].

9. Conclusions

It is critical in modern animal production systems to shift the status from survival to creation; that is, minimize the impacts of chronic inflammation and excessive stress so that chickens can utilize their energy for growth rather than defense. Although there is no “magic bullet” for preventing the multifactorial conditions associated with chronic stress, numerous studies have shown that alternative products, such as probiotics, direct-fed microbials, prebiotics, and phytochemicals, can help to improve intestinal microbial balance, metabolism, and gut integrity. These feed additives have been demonstrated to have anti-inflammatory, antioxidant, immunological modulatory, and barrier integrity-enhancing characteristics. To meet their health and productivity goals, poultry farmers who have eliminated antibiotics from their production systems may utilize a combination of alternative products in conjunction with enhanced management methods, rigorous biosecurity, and effective immunization programs. The relevance of dietary items and their quality, in addition to the absence of Mycoplasma spp. and Salmonella spp. from genetic lines, cannot be overstated. Any kind of stress induces intestinal inflammation, oxidative stress, and lipid peroxidation of vital cellular components, such as the cell and mitochondrial membranes. Damage to these organelles compromises cell homeostasis and the birds’ health and productivity. All animals have efficient mechanisms to avoid oxidative stress, such as glutathione peroxidase or superoxide dismutase. Nevertheless, chronic stress and chronic inflammation can overload the bird’s system. Antibiotic-free poultry production systems employ alternative natural products to reduce the effects of inflammation, colonization risk, and transmission of food-borne pathogens. These products also serve as strategies to maintain human and animal health and food safety in poultry production systems.

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Awad Shehata
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