Steering microbiota to support immunity

By Yvonne van der Horst (global technical manager Selko Feed Additives), Juan Antonio Mesonero Escuredo (global product manager Selko Feed Additives) and Mark Bouwens (researcher, Nutreco R&D)

Evolutionary processes have led to a beneficial relationship between the hundreds of microbial species in the intestinal tract of mammals and their host. Under healthy conditions, there is a stable balance between the different species in the microflora, which is based on mutual tolerance and optimal antagonism. There is a very close interaction between the intestinal microflora and the immune system. Therefore, it is crucial to maintain a healthy status of the intestine. This will result in better systemic health and thereby in optimal animal performance.

Adaptive immune system

Already in the earliest embryo stages, the different elements of the immune system start to develop. The innate immune system provides immediate defence against external threats and is comprised of anatomical barriers, such as epithelial surfaces, chemical components, such as the complement system, and cellular components, such as macrophages, that can directly attack and kill pathogens. The intestine is part of this innate immune system and very important in the development of the adaptive immune system. This adaptive immune system is dependent on signals from the innate immune system and takes time to develop an effective reaction, but can confer long-lasting or protective immunity to the host. The mucosal immune system comprises the immune tissues found in a variety of organs which are the main portals for entry of foreign microorganisms into the body, such as the nose, mouth and intestine. Since the intestine has a huge surface area, it is a very important physical barrier between the organism and a multitude of microorganisms. At birth, the neonate’s mucosal immune system is relatively undeveloped, but the colonisation of intestinal flora accelerates its development, providing the immune system with signals it learns to see as neutral, beneficial or harmful.

Balanced intestinal microbiota

Immediately after birth, bacteria from the maternal faeces, the environment and the diet will colonise the intestine. This results in a complex and dynamic microbiota population inhabiting the intestine. The microbiota make a number of key contributions to host health, including enhancing digestive efficiency, promoting proper immune system development and limiting pathogen colonisation. In order to make optimal use of these effects it is crucial to ensure a high diversity in the microbial population. The innate and adaptive components of the intestinal and mucosal immune system interact to mediate homeostasis between the microbiota and the host under normal conditions. The intestinal wall, comprising the epithelial layer and the inner and outer mucus layer, is an important physical barrier against bacterial invasion (Figure 1). The outer mucus layer is rich in bacteria, whereas the inner layer is resistant to bacterial penetration due to the higher viscosity of the mucus and the antimicrobial proteins that are produced by enterocytes in the epithelial layer. These enterocytes, together with the tight junctions that hold these cells together prevent bacterial invasion, while allowing nutrient flux into host tissues. Intestinal microbes can hydrolyse dietary polysaccharides that would otherwise be indigestible, therefore they allow flexible adaptation to dietary changes. The microbiota in the intestine also contribute to a healthy immune status of their host. They provide instructive signals for the development of key lymphocyte subsets and support the development of intestinal T and B cells. Besides that, microbiota impact the outcome of systemic immune responses by determining the ratio of Th1 and Th2 effector cells which help the activity of other immune cells by releasing T cell cytokines. These help to regulate immune responses to external challenges such as intracellular micro-organisms or parasites. Intestinal microbiota can also play a role in protecting the host against invasion by pathogenic bacteria. First, they compete with the microflora for nutrients from the host diet, thereby reducing colonisation of intestinal pathogens. Secondly, intestinal microbes also stimulate immune responses (e.g. triggering the expression of antimicrobial proteins through stimulation of Toll-like receptors) that are cross-protective against pathogens, thereby reducing invasion of for example Salmonella spp.

Healthy intestinal tract

In the case of stress situations such as weaning or diet changes, the intestinal health status is challenged. In these situations, microbial diversity might be impaired and there might be more space for harmful bacteria (both Gram negative and Gram positive species) to develop. It is known that intestinal bacteria are producing organic acids, such as acetic acid, lactic acid and butyric acid, which are able to reduce growth of unfavourable Gram negative bacteria. Besides that, specific organic acids contribute to a strong and healthy gut wall. Therefore, additives based on organic acids support the natural mechanisms for keeping the intestine healthy. Density and diversity of the intestinal microbial population increases from the upper towards the lower intestinal tract. Free organic acids in feed or drinking water create unfavourable conditions for bacterial growth. As a result, uptake of bacteria by the animal and thereby the risk of undesirable bacteria reaching the intestines is reduced. Organic acids in a buffered form which can be applied through feed or drinking water, will be released in the small intestine. These organic acids are known to reduce growth of Gram negative bacteria, therefore they support a healthy microbial balance in the small intestine.

Use of synergistic blend of acids

The upper part of the small intestine is dominated by Gram-positive bacteria. The cell wall of Gram-positive bacteria has a different structure compared to Gram-negative bacteria, which makes it more acid tolerant. Medium chain fatty acids (MCFA) are able to destabilise the peptidoglycan layers and interfere with respiratory capacity and ion transport of Gram positive bacterial cell walls, resulting in reduced proliferation and cell death. Organic acids and MCFA are quickly absorbed in the upper small intestine, therefore limited effect of these acids is shown in the lower intestine. Fat-coated or target release acids will pass the stomach and upper small intestine and will be released in the lower part of the intestine. Studies have shown that a blend of target release acids increased the microbial diversity in the jejunum of piglets compared to a control group (Figure 2).

With this synergistic combination of acids, the microbiota throughout the intestinal tract of monogastric species can be managed, thereby contributing to a healthy microbial balance in the intestine. Since we know that the microbiota are strongly related to the immune status in the gut, we can indirectly contribute to a healthy immune system and thereby to optimal performance of your animals.

[Source: AllAboutFeed Vol 22 nr 10, 2014]