Microbes In The Intestine: Friend Or Foe?

The intestinal mucosa forms the largest surface area of the human body. Unfolded, it would occupy approximately the area of a tennis court. It represents an interface between the body and the environment, and is therefore vulnerable to pathogens and worm infections. With an estimated 400 million infected schoolchildren, worm infections are one of the main diseases in developing countries. The sequelae include malnutrition, anaemia, delayed growth and retarded development of the cognitive faculties.

The immune system constantly under decision pressure

Nicola Harris, Professor at the Institute of Integrative Biology of ETH Zurich, is a specialist in the area of intestinal diseases caused by microbes. Harris explains that “As a result of the flimsy barrier between the intestine and the environment, the intestinal mucosa is constantly exposed to foreign substances and must be able to trigger a robust immune response to them.” At the same time, the mucosa must recognise whether harmless so-called commensal germs are involved, which live in symbiosis with humans, or dangerous or even lethal pathogens. Harris adds that, “The intestinal mucosa’s immune system is therefore faced with an enormous challenge. It must constantly decide when it must mount a counterattack against an inflammation that keeps the pathogenic germs in check by means of an activated defence response or when it needs to maintain the status quo in which humans and “useful” bacteria live in symbiosis.”

She says that the commonest intestinal microbes in mammalian evolution are symbiotic bacteria and worm infections. This is why Harris and her team research the different aspects of the immune defence in the intestine to understand the interaction between humans, commensal bacteria and worm infections.

In her latest research study, in collaboration with an international research team, she studied how humans build up an immune defence against infections by the worm Heligmosomoides polygyrus (Hp) which, although it leads to a chronic illness, limits the parasite’s infestation and spread, and how active immunisation occurs. From the knowledge gained, the researchers hope to be able to develop a vaccine against this parasite.

Multiple infections yield protective immunity

Working on mice, the scientists successfully tracked how an immune response arises in the body as a result of the infection. It became apparent that a mixture of what are known as polyclonal antibodies, i.e. non-specific antibodies, is formed after infection with the parasites. Specific antibodies – comparatively few of them – form only after multiple infections. In their experiments, the researchers were able to show that the polyclonal antibodies reduced the fertility of the adult worms and thus their egg production.

From this, the scientists can conclude that the polyclonal antibodies play two roles. On the one hand, the parasites are allowed to become chronic and practically to live in symbiosis with humans, but, on the other, the parasite infestation and its extent are limited. However, they also suspect that the formation of non-specific antibodies is responsible for the delayed formation of parasite-specific antibodies and thus ensures that the worms survive for a certain period of time. According to the researchers, both types of antibody play a key role: the non-specific antibodies limit the worms’ fertility whilst the specific ones yield immune protection against new infections.

Harris says, “This study yielded a solid scientific foundation and gave us optimism in our search for an effective vaccine against worm infections in the intestine.” The fact that the non-specific formation of antibodies allows the parasite to fool the immune system shows that conventional immunisation strategies will be ineffective in this case.

Mother’s milk confers protection

In an earlier study, the researchers had discovered that specific antibodies are passed on to infants through their mother’s milk, thus protecting them against infections. This is especially important because such infections can have a fatal outcome in small children and babies. Harris explains that, “The two studies show that a synthetic vaccine that protects people can be manufactured if the correct proteins of the parasites are chosen, and that the protection is passed on to babies through their mother’s milk.”

Infectious worm

Heligmosomoides polygyrus is a bright red threadworm measuring 5 – 20 millimetres that often implants itself in the human intestine by forming cysts. The parasite has a direct life cycle. The eggs are excreted via faeces and reach the larval stage after two days. The larvae are 300 μm long and become infectious after about three more days. As soon as the worm larvae have infected the human body and have reached the adult stage, they lay eggs. The full life cycle from egg to egg lasts at least 15 days. The female worm has a life expectancy of about eight months in its host.