A pig’s microbiota – a result of many factors

By Dr Marie Lewis, Lecturer in Gut Immunology and Microbiology, University of Reading, UK

A great deal of scientific research has been carried out to further our understanding of the interactions which occur between pigs and their pathogens. Over the years this has led to improved husbandry, medication and disease control. However, more recent studies indicate that the commensal bacteria residing in the gastro-intestinal tract have far more influence over host health and disease than previously thought. Collectively, these bugs are referred to as the ‘gut microbiota’ and there are somewhere in the region of 1,000-3,000 different species present.

The gut microbiota is an essential requirement for host health and it performs many functions. These include;
driving intestinal development, strengthening intestinal barrier function and controlling epithelial cell proliferation; the provision of enzymes which increase the value of food; metabolism of non-digestible foods to produce nutrients useful to the host; and synthesis of vitamins which cannot be consumed or generated by the host.

Protection

The microbiota also helps protect the host against intestinal pathogens through competition for nutrients and ecological niches, by occupying the host adhesion receptors required for pathogen colonisation and invasion, and by stimulating the host to produce antimicrobial peptides against such pathogens. In addition, one of the most important functions of the microbiota is to drive immune development in the young piglet. Although this occurs primarily in the gut, once developed the immune system is present throughout the entire pig.

The newborn piglet has few immune cells and immune tissues have not yet developed. Over time and in response to antigenic challenge, primarily from the gut microbiota, different types of immune cells increase in numbers and activity and immune tissues develop in a distinct way. This is known because piglets kept in sterile conditions do not have any bacteria in their gut and their immune system fails to develop. As soon as these sterile piglets are places in an environment containing bacteria, their intestines colonise and immune development is triggered.

It is also known that particular families of bacteria drive the development of the different arms of the immune system which protect the piglet against different types of disease agents, such as viruses, pathogenic bacteria and parasites. For example, Segmented Filamentous Bacteria (closely related to Clostridia) cause the expansion of an immune cell population called T-helper 17 cells. These immune cells are proinflammatory and orchestrate the immune response against enteric pathogens including Escherichia coli.

On the other hand, another species within the normal microbial population of the gut, Bacteroides fragilis, drives the expansion of a different subset of immune cells, the regulatory T-helper cells. As the name suggests, these cells help to regulate the immune system and prevent undesirable immune responses against harmless antigens. In addition, the Regulatory T-helper cells return the immune system to normal once an infection has been cleared, thus limiting energy expenditure.

The interactions between the micro-biota and the host immune system are extremely complex and we are only just beginning to scratch the surface. Nevertheless, it is clear that the immune system must develop in the correct way in young animals otherwise they may become vulnerable to particular disease agents in later life.

In addition to failing to protect the piglet against infectious diseases, if the immune system develops in the wrong way it may try to fight off harmless antigens, say from food, which is energetically expensive and can lead to a reduced growth rate, or reduced reproductive potential. Because the development of the immune system is driven by the microbiota, it is very important to have the right ‘mix’ of bacteria to generate the correct ratios of all the arms of the immune system i.e. a competent immune system, which responds appropriately to the various stimuli it comes into contact with.

Early-life environment

The early-life environment affects the pattern of microbial colonisation, or the families of bacteria which enter the gut, and therefore how the immune system develops. From birth onwards, piglets acquire bacteria from their immediate environment and it has been shown that rearing piglets under different conditions causes the different arms of the immune system to develop at different rates.

For example, piglets nursed by their sows on a commercial outdoor farm had a much higher regulatory T-helper cell to inflammatory T-cell ratio compared to littermates reared under high hygiene conditions (Figure 1). This had functional consequences because these outdoor farm-reared piglets had reduced immune responses to harmless soya protein at weaning.

The previous example compares piglets reared under very different conditions; farm verses a high-hygiene, fumigated isolator in which the piglets were individually housed on flatbed units which were thoroughly cleaned every day.

Indoor or outdoor

Research carried out between the Universities of Bristol and Aberdeen, UK, also compared immune development between the same breed of piglet reared in either indoor farrowing units or outdoor, free-range farms until they were 28 days old. In this trial, the indoor-reared piglets had fewer immune cells involved with the initial presentation of antigens to the rest of the immune system than their outdoor counterparts at five days old. However, by 28 days, this had reversed and it was the outdoor-reared piglets which had increased potential to present antigen.

This is important because the presentation of antigen is the very first step in generating an appropriate immune response and it initiates the recruitment of the different types of immune cells necessary to fight off different infectious agents.

An immune system which rapidly produces large numbers of cytotoxic T-cells might be very useful against viral infections such as African Swine Fever, but would offer little protection against Ascaris suum. This research has also shown that the environment during the very first day of life has a major impact on the families of bacteria which initially colonise the gut and these bacteria change the conditions in the gut which make it more or less attractive for the families of bacteria which arrive later on. For example, piglets have been taken from their sows on indoor and outdoor farms at just one day old and have been mixed all together in the same clean, fumigated environment for eight weeks.

Instructing immune systems

The research team then looked at the antigen presenting cell and T-helper cell complexes which form during antigen presentation. The team found that the piglets which originated from the outdoor farm instructed their immune systems about the antigens present in the environment in a very different manner to those piglets which originated from the indoor farm.

This difference was dependent on the environment during the first day of life, eight weeks after the piglets had been placed in the same environment. This study demonstrated that environmental influences during the very first day of life can have a sustained influence over how the immune system develops and this was linked to the bacteria acquired from the environment during this short window of time.

It is becoming increasingly clear that in order to maximise productivity, it is essential that the right mix of gut bacteria colonise the neonatal piglet in order to generate an appropriate immune system which fights off different types of diseases without wasting energy.

It seems that the right rearing environment is pivotal in achieving a competent immune system. It is also becoming apparent that early-life antibiotics completely alter the families of bacteria which initially colonise the gut.

In turn, this impacts on the families of bacteria which are present in the adult microbiota and has implication for long-term health. Piglets which receive antibiotics during the neonatal period are not only more susceptible to some types of diseases as they grow, but this practice is also a major factor contributing to the rapid rise in antibiotic resist bacteria. Antibiotic resistant bacteria are becoming a serious problem in both animal production and human health. In addition, current evidence suggests that complex interactions occur between the immune system, the intestinal bacteria and metabolism. This means that disrupting the pattern of gut colonisation during early life is likely to have metabolic implications too.

Maybe in the future instead of using antibiotics during early-life, which we know has such fundamental, long-term implications we ought to be giving newborn piglets the right mix of bacteria in the first place in the form of probiotics. However, more research is needed in this area so we can identify the best mix of bacteria which result in the best health outcomes for piglets.

Pig Progress 29.9