Homeostasis – The golden path to efficient poultry production

The gut harbors the largest part of the cells of the immune system and is home to a wide variety of commensal bacteria. In the highly intensive broiler industry where antibiotics as growth promoters are banned, it is critical to boost gut health by promoting nutritional strategies focusing on intestinal barrier strengthening, oxidative stress reduction, pathogen prevention and microbiota and immune modulation.

Dr. Ruth Raspoet
Poultry R&D Manager
Phileo by Lesaffre

The gut is the largest organ of the body that is exposed to the external environment while exerting several complex functions. The most well-known function of the gastro-intestinal tract is digestion of feed and absorption of nutrients. Besides digestion, the intestinal mucosa functions as a barrier preventing the passage of toxins and pathogens. The gut harbors the largest part of the cells of the immune system and is home to a wide variety of commensal bacteria. As an optimal gastrointestinal functionality is essential for an efficacious and sustainable animal production, it is becoming globally accepted that gut health is an important physiological condition intertwined with overall health (Bischoff 2011). In 2016, gut health was defined as ‘the absence/prevention/avoidance of disease so that the animal can perform its physiological functions in order to withstand exogenous and endogenous stressors (Kogut 2016). Later on, Celi et al., proposed that gut health would be defined as ‘a steady state, where the microbiome and the intestinal tract exist in symbiotic equilibrium, and where the welfare and performance of the animal are not constrained by intestinal dysfunction’. It shows that holistically, gut health is the result of complex interactions of various components of the gut, the host animals, and the environment to maintain homeostasis (Wickramasuriya et al., 2022). A variety of factors including management, pathogen pressure and diet can affect the gut health status of the animal, leading to microbiome dysbiosis, disturbance of the intestinal homeostasis with gut mucosal barrier leakage and inflammation (Zhu et al. 2021). Consequently, in the highly intensive broiler industry where antibiotics as growth promoters are banned, it is critical to boost gut health by promoting nutritional strategies focusing on intestinal barrier strengthening, oxidative stress reduction, pathogen prevention and microbiota and immune modulation.

Based on advanced, science-proven yeast solutions, Phileo by Lesaffre has developed a dedicated gut health program focusing on the 4 key specific pillars mentioned above, to help birds to maintain homeostasis, be more resilient to stresses and reach greater production performance.

Figure 1. Goblet cell numbers significantly increased by yeast postbiotic Safmannan at different timepoints (adapted from Pascual et al., 2020)

EPITHELIAL BARRIER STRENGTHENING
An essential function of the intestinal mucosa is to act as a physical barrier between gut luminal content and the remainder of the body. The physical intestinal barrier depends on a variety of mucosal structural components that confer the property of selective permeability with free exchange of water, ions and macromolecules between the intestinal lumen and the underlying tissues. The luminal surface of the intestinal mucosa is lined by a hydrated gel, composed of mucins secreted by goblet cells. This layer prevents large particles and intact bacteria from coming into direct contact with the underlying epithelium. Underneath the mucus layer, there is the epithelial monolayer as primary determinant of the mucosal barrier. An intact epithelium restricts the passage of hydrophilic solutes but to further limit transmucosal flux, the paracellular space needs to be sealed as well. This task is regulated by a series of intracellular junctions (tight junction, adherens junctions and desmosome) who together form the apical junctional complex (Odenwald and Turner 2017). An experiment performed in 2020 by Pascual et al., showed that supplementation of the yeast postbiotic Safmannan® containing >20% mannans and >20% β-glucans could increase the goblet cell density (Figure 1).

Figure 2. Mucin 2 expression is significantly increased by yeast postbiotic Safmannan, under challenging or normal experimental conditions.

These results are in line with another study where the same yeast postbiotic was able to induce the mucin expression. In the last study, a factorial design was used to elucidate the effect of the postbiotic with and without heat stress. In both the non heat stress and the heat stress treated groups an increase in mucin production was seen in the animals supplemented with the postbiotic. This leading to a better protection of the enterocytes and reduction of the possibility for pathogens to interact with the epithelial cells (Bungo – WPC 2020) (Figure 2). Additionally, a similar heat stress trial was performed by the same research group and showed that heat stress is inducing leaky gut symptoms with impairment of the tight junctions. Whereas supplementation of the yeast postbiotic under these conditions could strengthen the tight junctions and prevent the leakage of harmful substance into the systemic system of the animals (Bungo – WPC 2020).

Figure 3. Broiler final body weight increased significantly by organic selenium enriched yeast Selsaf, compared to other mineral and organic sources of selenium.

OXIDATIVE STRESS REDUCTION
Oxidative stress occurs when excess of reactive oxygen and nitrogen species (RONS) are creating an imbalance between the pro- and antioxidant system which in turn disrupts physiological processes and cause disease. Consequently, intestinal oxidative stress plays an important role in the early stage of intestinal injury. It triggers abnormal cell proliferation, growth stagnation and apoptosis leading to intestinal barrier dysfunction and inflammation (Wang et al 2020). A good antioxidant system is thus of outmost importance to balance the production of RONS, or neutralise them, while still guaranteeing their biological function. Seleno-enzymes e.g., glutathione peroxidase (GPx), are known for their actions in the antioxidant system and are requiring the trace element selenium for their activity. As selenium is a trace element, it is provided within the animal feed in inorganic or organic forms. The organic forms include synthetic selenomethionine (SeMet) or selenized yeasts, rich in natural Se components. The highly consistent organic selenium enriched yeast, Selsaf®, is obtained from the specific cultivation of a proprietary Saccharomyces cerevisiae (CNCM I-3399) and contains SeCys and SeMet from which the selenium atom can be used for the construction of animal seleno-enzymes. The high selenium values in blood after Selsaf administration show that the active selenium components in Selsaf® are efficiently absorbed by the gut. This leading to a higher bioavailability of the selenium with higher activity of the seleno-enzymes like GPx and thus a better functioning anti-oxidant system.

Figure 4. Laying performance greatly improved by organic selenium enriched yeast Selsaf, compared to other mineral and organic sources of selenium.

Furthermore, trials comparing the efficacity of the organic selenium enriched yeast Selsaf with synthetic organic SeMet products have demonstrated that Selsaf can greatly improve the production capacities of both broilers and layers (Figures 3 and 4).

MICROBIOTA MODULATION AND PATHOGEN PREVENTION
In cells, the microbial inhabitants of the intestine largely exceed those of the host and mediate key physiological processes for the health of the host. The microbiota exhibits important functions in digestion, development and regulation of the gut associated lymphoid tissue (GALT) but also competes with pathogenic invaders. At the Phylum level, over 90% of the phylogenetic categories in the cecum either belong to the Phylum Firmicutes (Clostridium, Enterococcus, Lactobacillus and Ruminococcus genera) or to the phylum Bacteriodetes (Bacteroides and Prevotelle genera), while at the species level there are huge differences in microbiota composition. Nevertheless, one constant characteristic of a healthy microbiota is that has a high diversity. Moreover, within the same host, the composition of the microbiota is influenced by a variety of factors. In some cases, this can even lead to dysbiosis, an undesirable alternation of the microbiota resulting in an imbalance between protective and harmful bacteria populations. Dysbiosis was practically unknown until the ban of AGPs, but since then one of the most challenging problems in broilers (Ducatelle et al., 2015). Dysbiosis can also be caused by the diet and especially in times when good quality raw materials are expensive and are not always available; this can be a problem. Nevertheless, a study performed in Brazil showed that the yeast postbiotic Safmannan® was able to increase the microbiota diversity of broilers receiving a low-quality diet. Significant increases in beneficial genera such as, Roseburia, Ruminococcus torques, Eubacterium hallii and Shuttleworthia were observed while Enterobacteria numbers decreased (Figure 5).

Figure 5. Higher microbiota diversity observed in broilers in the yeast postbiotic Safmannan group

Similar results were seen in a turkey trial where administration of the postbiotic led to a significantly higher abundance of firmicutes and actinobacteria in the supplemented group compared to the control in the feces after 21 days. Additionally, the microbiota of the treated animals was characterized by a lower abundance of Proteobacteria, attributed to the class of Gammaproteobacteria (mainly Enterobacteriaceae such as Klebsiella, Shigella, Acinetobacter, Escherichia, Enterobacter, Erwinia and Serratia). After 85 days, the supplemented group exhibited higher abundance of health promoting species such as Lactobacillus, Clostidium bifermentans and Pediococcus acidilactici (Zampiga – WPC 2020)(Figure 6).

Figure 6. The feces of turkeys in the Safmannan group showed a higher abundance of health promoting microorganisms in comparison to the control group.

PATHOGEN PREVENTION
The decrease in Enterobacteriaceae could partially be explained by the composition of the yeast postbiotic due to the presence of the α-mannans who will adhere to type-1 fimbriae of pathogenic bacteria including Salmonella, making it more difficult for these pathogens to colonize the intestinal epithelium (Posadas et al., 2017) (Figure 2).

This is confirmed in a Salmonella Typhimurium challenge model where administration of Safmannan® reduced the Salmonella colonization in ceca (P=0.001) on D28 of the trial. A reduced colonization of Salmonella in the liver (P=0.038) also indicates that an increased intestinal health reduced the translocation of the pathogen to systemic organs (data on file) (Figure 7).

Figure 7. Salmonella colonization in ceca was significantly reduced in the Safmannan group

VACCINE POTENTIATION
Within the lamina propria of the gut, there is a sophisticated immune system further protecting the host from infectious diseases. The gut associated lymphoid tissue (GALT) plays a major role in the gut immune response including both innate and adaptive functions. The GALT includes organized lymphoid structures such as the bursa of Fabricius, cecal tonsils, Peyer’s patches, Meckel’s diverticulum and lymphocyte follicles. Although the GALT in newly hatched chicks is quite underdeveloped, a fully functional immune system is formed within 4 weeks after hatch. Enterocytes express pattern recognition receptors (PRRs) which sense conserved pathogen molecular signatures while remaining non-responsive to the commensal microbiota. As a consequence, various immune pathways to initiate microbial killing are activated. Additionally, enterocytes secrete a large variety of antimicrobial peptides into the intestinal lumen and plasma cells are secreting IgAs to neutralize pathogens and facilitate their removal from the gastro-intestinal tract (Kogut et al., 2017; Wickramasuriya et al., 2022).

Figure 8. Antibody titers against Newcastle Disease was increased in birds in Safglucan group, compared to control group

In order to modulate the immune system and improve intestinal health, β-glucans derived from yeast have shown to be very efficacious. β-glucans from yeast are natural polysaccharides consisting of a (1,3)-beta-glycosidic backbone with β-(1,6)-linked side chains of various lengths that are recognized by innate immune cells as microbial-associated patterns through the Dectin-1 receptor (Walachowski et al., 2017). β-glucans have also shown to increase phagocytic activity and the production of antibody titers (Jacobs et al., 2017).

The effect of β-glucans on the production of antibody titers was seen in a Salmonella challenge experiment, where administration of Safglucan® containing more than 50% of β-glucans has led to a higher production of secretory IgA against Salmonella LPS and flagellin.

Thanks to the potential of β-glucans to increase antibody titers, yeast β-glucans Safglucan® is also very efficacious vaccine potentiator. This is demonstrated in several vaccination trials, were the administration of Safglucan® led to the increase in titers against Newcastle Disease (ND). Safglucan® increased anti-ND specific antibodies in serum when supplemented through the diet (Figure 8).

CONCLUSION
The withdrawal of antibiotics from the poultry industry has made it clear that gut health is an important factor determining animals’ performance but also animal health and wellbeing. Yeast based advanced solutions have shown to be able to modulate gut health by interfering on several aspects e.g. stress and pathogen reduction, epithelial barrier strengthening and microbiota and immune modulation. As such yeast based nutritional products assurance to maintain animals’ performance and to meet global increasing food demands for high quality animal proteins while also improving animal health and welfare.

Phileo by Lesaffre’s source references for this article are available upon request.