A thorough review of phytogenic feed additives in non-ruminant nutrition: production, gut health, and environmental concerns

Analyzing the impact of PFAs on intestinal morphology can provide insights into their role in enhancing gut health and structural integrity. Phytogenic compound positively influence nutrient digestibility by minimizing competition for nutrients between the bird and its gut microflora, and by potentially stimulating intestinal enzyme activity and inducing alterations in gut morphology [19]. PFAs contribute positively to intestinal morphology primarily by diminishing inflammation, fostering cellular growth, and potentially influencing mortality control [29]. Wang et al. [30] conducted research indicating a linear rise in duodenal mucus layer thickness in broilers with escalating concentrations of dietary PFAs. Grape-derived dietary polyphenols alter the gut morphology and intestinal microflora while enhancing the biodiversity of intestinal bacteria in broiler chicks [31]. The morphometric parameters of jejunum CD and villi height (VH) were evident only in 21-day-old chickens, with a significant interaction observed only in chickens fed a maize diet supplemented with plant origin active substances [32]. Additionally, the inclusion of PFAs led to an elevation in VH throughout the small intestine in poultry [33] and pigs [34]. Flavonoids from plants, specifically genistein (5 mg/kg) and hesperidin (20 mg/kg) were administered to broilers challenged with lipopolysaccharide (LPS), demonstrating their efficacy in immune stimulation and enhancing gut morphology [35]. In their study, Reisinger et al. [36] noted that supplementing the diet with a PFA based on EOs resulted in heightened villus length (VL) and increased goblet cell density in the mid-ileum section of the small intestine in broilers subjected to a mild coccidial vaccine challenge. Birds supplemented with dietary genistein and hesperidin exhibited a significant increase in gut VL and villus width on days 21 and 42, and a decrease in CD in the duodenum on day 42 and in the ileum on day 21, irrespective of the LPS challenge [35]. Increased VH could also enhance the activity of enzymes released from the villus tips, potentially leading to improved digestibility [37].

The effects of PFAs on gut barrier integrity are crucial for their potential to improve intestinal health and strengthen the body’s defense against pathogens. You et al. [38] observed improved performance in newborn pigs with the dietary addition of flavonoids, noting benefits such as the adjustment of beneficial gut bacteria, enhanced gut epithelial structure, better barrier functionality, and increased immune performance. Dietary polyphenols, by promoting Igs and reducing the release of pro-inflammatory cytokines may further improve gut health and integrity in monogastric animals [39]. Moreover, Yuan et al. [40] found that incorporating flavones extracted from Eucommia ulmoides leaves into the diet improved the intestinal morphology and integrity of challenged pigs by enhancing intestinal barrier function. Additionally, eckol has been identified as a potential feed supplement for influencing intestinal barrier functions, wound healing, and oxidative stress, leading to enhanced growth during the transition from suckling to weaning [41]. Enhanced pre-cecal digestive capacity decreases the influx of fermentable substances into the hindgut, thus restraining postileal microbial growth and the expulsion of bacteria in feces [3]. According to Kroismayr et al. [20], a reduction in immune defense activity in the gastrointestinal tract (GIT) aligns with concurrent enhancements in zoo-technical performance, gut microbial composition, fermentation products, and apparent nutrient digestion facilitated by EOs.

Exploring the impact of PFAs on the intestinal microbiota is essential for understanding their role in influencing gut microbial communities and enhancing digestive health. PFAs were documented to enhance the production of mucus in the intestines of broilers, with the assumption that this action could hinder the attachment of pathogens, consequently aiding in the stabilization of microbial balance in the gut [32]. The antimicrobial properties of bioactive substances in herb extracts arise from the hydroxyl group, which can bind to bacterial protein molecules, leading to the release of vital cell components [42]. For example, the dietary supplementation with carvacrol, cinnamaldehyde, and capsaicin enhances mucus secretion, forming a protective barrier in the gut, which may reduce epithelial adhesion and intestinal populations of Escherichia coli, Clostridium perfringens, and fungi in chickens [32]. Carvacrol and thymol induce the collapse of the outer membrane in Gram-negative bacteria by releasing LPS, increasing the permeability of the cytoplasmic membrane to ATP, and depolarizing the cytoplasmic membrane [43,44]. These compounds, found in thyme and oregano, exhibit antimicrobial properties by penetrating cell membranes and mitochondria, leading to cell lysis [43]. Mountzouris et al. [45] found that including PFAs (125 and 250 mg/kg) diet led to beneficial modulation of caecal microbiota in 42-day-old broilers, with a linear increase in Lactobacillus, Bifidobacterium, and Gram-positive cocci concentrations, while caecal coliforms at 14 days of age were significantly lower compared to the antibiotic Avilamycin. Mitsch et al. [46] also suggested that PFAs play a role in stabilizing the gut microbiota, consequently decreasing the colonization of clostridia within the GIT. Thus, PFAs significantly modulate the intestinal microbiota by enhancing beneficial bacteria and reducing pathogenic bacteria, thereby stabilizing gut microbial communities and promoting digestive health in non-ruminant livestock.

Phytochemicals exert health-promoting effects by enhancing the host’s defense mechanisms against microbial infections. The fundamental action of phenolic compounds on immune function includes stimulating the production of Igs and cytokines, enhancing phagocytosis, and promoting the release of interferon (IFN)-γ [47]. In vitro studies have demonstrated that phytochemicals from sources such as dandelion, mustard, safflower, thistle, turmeric, reishi mushroom, and shiitake mushroom inhibit tumor cell growth and stimulate innate immunity. These effects are confirmed by in vivo trials showing that PFAs can modulate immune responses through multiple mechanisms [48]. For instance, supplementation with PFAs containing carvacrol primarily affects the cecal microbiota by increasing beneficial bacteria like Bacteroides spp. and Clostridium clusters IV and XIVa, which contribute to gut function and butyrate production [49]. Additionally, incorporating phenolic-rich soy isoflavones into the diet resulted in enhanced immune function, reduced incidence of diarrhea, and decreased plasma endotoxin levels in piglets challenged with LPS [50]. Likewise, tea polyphenols demonstrated the ability to modulate T lymphocyte activities, improve the CD4+/CD8+ ratio, facilitate immune recovery from oxidative stress-induced damage, enhance cell-mediated immune response, and reduce the secretion of pro-inflammatory cytokines like IFN-γ, emphasizing their immunomodulatory potential [51]. Hence, PFAs enhance host defense mechanisms and immune responses through various pathways, including the modulation of intestinal microbiota, stimulation of Ig and cytokine production, and reduction of pro-inflammatory cytokine secretion, thereby improving overall health and resilience against infections in livestock animals. Table 1 illustrates the effect of PFA on the immunity of non-ruminants.

Inflammation is a natural protective reaction triggered by tissue injury or infection to combat microorganisms and eliminate dead or damaged host cells [52]. PFAs are known to possess anti-inflammatory properties that can help modulate immune responses and reduce oxidative stress in non-ruminant animals. EOs like chamomile have anti-inflammatory effects and have been traditionally used for centuries to treat symptoms of eczema, dermatitis, and other notable irritations [53]. These EOs exert their anti-inflammatory benefits by interacting with signaling pathways involving various cytokines and regulatory transcription factors, and by regulating the expression of genes related to inflammation [54]. For example, resveratrol, when administered at 500 mg/kg as a phenolic compound, effectively modulated immune function and inflammatory response in yellow feather broilers experiencing heat stress, achieved through the inhibition of various signaling pathways including nuclear factor-kappa B (NF-κB), MAPK mitogen-activated protein kinase, and phosphoinositide 3-kinase/protein kinase B [55]. Alkaloids enriched with phenolic compounds can influence gut health by modulating the inflammation cascade through the inhibition of NF-κB activation [56]. Dietary carvacrol EOs, administered at 200 μL/L, reduced the expression of inflammatory cytokines in broiler chickens challenged with LPS, underscoring the anti-inflammatory role of carvacrol [57]. Lavender EO supplementation increased the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) enzymes, which are crucial for defending against oxidative stress [58, 59]. Phenolic compounds from the Labiatae plant family have been shown to enhance the oxidative stability of both pork [60] and poultry meat [61]. Feeding broiler chickens with Artemisia annua, a type of PFA, resulted in a significant reduction in thiobarbituric acid reactive substances values in both breast and thigh meat, suggesting the potential antioxidative properties of polyphenolic compounds or vitamin E in Artemisia annua [62]. Additionally, thymol supplementation reduced malondialdehyde levels in the duodenal mucosa, suggesting decreased fatty acid oxidation [63]. Mueller et al. [64] demonstrated that phytogenic substances such as broccoli, turmeric, oregano, thyme, and rosemary up-regulated antioxidant response element genes in the small intestine of broilers, indicating reduced oxidative stress. Agricultural residues serve as a valuable reservoir of polyphenols and antioxidant compounds, which can be beneficial as bioactive elements for animal feed [65]. Therefore, PFAs enriched with phenolic compounds and EOs offer significant anti-inflammatory and antioxidant benefits, effectively modulating immune responses, reducing oxidative stress, and improving the health and quality of livestock products.

PFAs influence several aspects of livestock performance, including the release of digestive juices and enzymes, immune system modulation, changes in intestinal morphology, and improvements in nutrient utilization, leading to enhanced overall performance [66]. Mahfuz et al. [67] noted that incorporating phenolic supplements into feed can positively affect antioxidant capacity, immune response, antibacterial properties, and overall production efficiency in pigs and poultry. For instance, adding 0.5 g/kg of anise seed, with anethole as the active component, to the diet notably enhanced body weight gain (BWG) and performance index in broilers; however, there were no significant effects on FI or feed conversion ratio (FCR) [68]. Furthermore, Choi et al. [69] documented a gradual increase in both the overall average daily gain and feed efficiency in weaning pigs. It was reported that incorporating quercetin in the diet at concentrations of 0, 0.2, 0.4, and 0.6% resulted in enhanced BWG and increased FI during the period of 0 to 35 days [70]. Administering 50 or 100 mg of garlic and onion to the diet of broiler chickens resulted in a notable increase in body weight [71]. Similarly, fenugreek seed supplementation at 1%, 2%, and 3% levels significantly improved FCR in broilers [72]. Another study indicated that adding 1 or 2 g of anise seed to a broiler’s diet resulted in enhancements in BWG and FCR, with no impact on FI [73]. Supplementing a low-protein diet with AJE showed promise in maintaining comparable growth performance by enhancing nitrogen digestibility and influencing the intestinal bacterial population in broilers [74]. Biswas et al. [75] observed a dose-dependent improvement in growth performance and nutrient utilization with increasing concentrations of gallic acid. Additionally, incorporating AJE into a low-protein diet maintained comparable growth performance and improved meat quality [76]. PFAs also positively impact nutrient digestibility, leading to increased total apparent dry matter and crude protein digestibility [77]. These improvements in feed conversion and growth efficiency are attributed to changes in gastrointestinal surface and enhanced digestive enzyme functionality [45]. The beneficial effects of phenolic content on growth may also stem from improved FI and enhanced nutrient absorption, which positively influence the intestinal epithelium [78].

Flavor, perceived through taste and smell, can be enhanced or altered in feed using plant ingredients like herbs, spices, and their extracts, thereby improving palatability and influencing the sensory properties of the diets [66]. Phytobiotics are primarily asserted to positively impact the flavor and palatability of feed, thereby boosting production performance [3]. EOs, which are volatile compounds responsible for the distinctive fragrance of their sources, are named after their origins [79]. Evidence suggests that incorporating PFAs into swine diets can enhance FI [20]. However, the effects of EOs on palatability can vary. For instance, feeding pigs EOs from fennel and caraway, or thyme and oregano, caused a dose-dependent decrease in palatability [80]. In a choice feed experiment, supplementing with fennel (100 mg/kg) or caraway oil (100 mg/kg) significantly reduced FI, indicating that these flavors may decrease palatability. This decrease in palatability may be attributed to the strong, distinctive aromas and flavors of these EOs, which can lead to feed aversion in pigs. High doses of certain EOs may also activate bitter taste receptors, further reducing FI. Conversely, aromatic EOs that enhance feed flavor and palatability can lead to increased voluntary FI and subsequent weight gain. Thus, the impact on flavor and palatability varies based on the type and dosage of PFAs used.

Research on dietary EOs has shown various impacts on meat quality and lipid oxidation. For instance, Javan et al. [81] assessed the effects of EOs (Zataria multiflora) on microbiological growth and lipid peroxidation in refrigerated broiler breast fillets. In the study by Hong et al. [33], birds in the EO group exhibited increased tenderness in breast meat and greater juiciness in thigh meat compared to the CON and AGP groups, likely due to the ability of PFAs to enhance protein metabolism and water-holding capacity. As reported by Ranucci et al. [82], adding a plant extract mix (a combination of oregano EO and sweet chestnut wood extract, 0.2%) to the diet decreased meat lipid oxidation in pigs, which can be attributed to the antioxidant properties of polyphenols that scavenge free radicals and inhibit oxidative damage. Similarly, Ghazaghi et al. [83] observed that incorporating Mentha spicata (1-4%) into the diet enhanced the meat quality of Japanese quail by improving muscle fiber integrity and reducing oxidative stress. The inclusion of EOs also led to an enlarged longissimus muscle area and reduced yellowness in meat [84], potentially due to their role in modulating muscle protein synthesis and reducing lipid oxidation. PFAs reduced saturated fatty acid (SFA) levels while increasing monounsaturated and polyunsaturated fatty acids, particularly lowering hypercholesterolemic SFAs like lauric, stearic, myristic, and palmitic acids [85,86], likely through their influence on lipid metabolism and enzyme activity involved in fatty acid synthesis. Increased quercetin levels in the diet positively affected breast muscle development, improved meat quality parameters such as cooking loss and drip loss, and enhanced blood profiles [87], possibly due to its ability to regulate muscle cell differentiation and maintain cellular integrity. Moreover, EOs have been shown to improve the oxidative stability of meat from broilers [88] by enhancing endogenous antioxidant enzyme activity and reducing lipid peroxidation. The enhancement of meat quality traits through dietary supplementation with PFAs is largely attributed to the antioxidant properties of phytogenic compounds. In contrast, Simitzis et al. [89] found that adding dietary oregano EO at doses of 0.25, 0.5, and 1 ml/kg of feed did not lead to improvements in the lipid oxidation status of pork. This variability in results could be attributed to species-specific differences in fatty acid composition and antioxidant enzyme activity between poultry and swine, as well as variations in the bioavailability and metabolism of phytochemicals.

PFAs, particularly EOs and herbal extracts, have shown potential in enhancing egg production and quality in laying hens through various mechanisms. For example, addition of 200 mg/kg of EOs from thyme, sage, or rosemary was found to increase the proportion of eggshell [90]. Incorporating peppermint (Mentha piperita) leaves into the diet of 64-week-old Hy-Line brown laying hens resulted in a notable increase in egg weight, egg production, and overall egg mass [91]. Additionally, a mixture of herbal EOs improved eggshell thickness [92], and herb blends increased the hens’ egg-laying capacity by 1.79% compared to the CON group [93]. These positive effects of PFAs may be attributed to their ability to enhance uterine health, increase calcium storage, and boost pancreatic secretions, thereby improving nutrient digestion and subsequently eggshell and egg quality [94]. However, there were no observed benefits in terms of relative shell weight when black cumin EO was added to the diet at three varying levels (1, 2, or 3 mL/kg) [90]. Similarly, adding oregano EO (50 or 100 mg/kg) to the diet at 32 weeks of age had no impact on egg quality attributes, such a yolk color score, Haugh unit, or shell thickness [61]. Similarly, the laying rate and the weight of settable eggs were not affected by an EO mixture at levels of 24, 36, or 48 mg/kg [95]. This discrepancy may be due to various factors such as the inherent variability of botanical composition, animal scenarios, environmental and management conditions, potential pathogen challenges, and the treatment technique used, which can alter the active substances and related compounds in the final product [3].

The impact of PFA administration on the biochemical markers in serum helps illustrate the body’s physiological status and nutrient metabolism. For instance, increased monocyte counts were observed in hens supplemented with fennel EO at 300 mg/kg [96], while higher lymphocyte numbers were associated with the inclusion of thyme powder at 0.2% [97], both of which serve as positive health indicators in laying hens. Supplementation of lavender EO reduced serum lipid parameters such as cholesterol and low-density lipoprotein cholesterol in broiler chickens [59]. Similarly, Pulicaria gnaphalodes powder decreased cholesterol and triglycerides [98], and a blend of oregano, anise, and citrus EOs lowered cholesterol levels [99]. In addition, supplementation of peppermint oil reduced serum cholesterol levels in laying hens [94]. Moreover, including a mixture of yeast and garlic extract supplements in broiler diets led to a progressive enhancement in immune function, characterized by a linear increase in blood IgG levels [11]. Anise supplementation in poultry feed was also found to enhance lymphocyte counts [68]. Furthermore, the blood profile revealed a significant linear decrease in cholesterol levels and a tendency for triglyceride levels to decrease with micelle silymarin (MS) supplementation [16]. Adding 0.06% MS to a corn-soybean meal-based diet for 12 weeks significantly enhanced production performance and egg quality, positively affecting aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase levels, and indicating improvements in albumin, triglyceride, and cholesterol levels [100]. Research indicates that PFA may inhibit the enzyme HMG-CoA reductase, essential for liver cholesterol synthesis, thereby potentially reducing cholesterol levels in the bloodstream [101]. Table 2 and Fig. 1 illustrates the response of non-ruminant animals to the phytogenic additive.

Fig. 1. Effects of phytogenic feed additives on non-ruminant animal health.

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