Axenic and gnotobiotic research

Microbiota and immune system

A vast number of bacteria, viruses, and fungi inhabit the inner and outer body surfaces, such as the intestine, the airways and the skin, of all healthy mammals. Bacteria constitute by far the most studied component of this microbiota and can predominantly be found in the lower intestine where they importantly contribute to host physiology. Gut bacteria help us digest food, produce essential vitamins and protect us from infection.

The “window of opportunities”

Colonization with mutualistic microbes starts principally at birth when the newborn makes contacts with the first bacteria in the birth canal. Within the uterus, the unborn child lives in a protected almost sterile milieu. The first bacteria to colonize the newborn will be those present in the immediate environment. For example, babies born by natural delivery have a different initial microbiota than those born through caesarian section, and during the first month of life breast or formula-fed infants harbor different gut bacteria. It seems to be this early stage of life that is of great importance to shape the intestinal microbiota and can influence a child’s later risk to develop allergies or autoimmune disorders. These effects of early life exposure and their consequences on immunity and allergic/autoimmune susceptibility can be monitored in animal models. For example, Researchers therefore often call this period the “window of opportunities” and many research studies nowadays concentrate on the microbial effects on the host during these early stages of life.

Gnotobiotic research

State-of-the-art to study the effect of microbiota on the host is the use of germ-free mice in comparison to defined colonized mice, so called gnotobiotic mice. Gnotobiotic models exist in different complexities ranging from mono-colonizations to microbiotas with up to 20 different bacteria. Well-established model microbiotas are the Altered Schaedler Flora (ASF) including 8 different bacteria as well as the stable defined moderately diverse mouse microbiota (sDMDMm2) which consists of 12 bacteria . Both low diversity and higher diversity models have their advantages, such as better in silico modeling possibilities in lower diversity microbiotas and the greater proximity of higher bacterial diversity to the natural situation. Gnotobiotic mice exhibit additional advantages compared to undefined specific pathogen-free mice even in studies that do not investigate the effect of the microbiota per se.

The gut-brain axis

In recent years, we have witnessed a dramatic increase in several immune-related disorders in the developed countries, including allergies, autoimmune diseases, and metabolic and neurological disorders. This is thought to be due to important changes in our life style, such as improved hygiene conditions, advances in medicine, drug consumption, diet changes, and smoking. Almost all of these factors affect the delicate and important balance between our body and the microbiota. These organisms have a metabolic and protective function and they educate the host immune system at all sites of our body. However, the exact mechanism involved in the systemic effects, especially at the level of the immune response in systemic organs, such as the central nervous system (CNS), induced by intestinal bacteria, remains poorly understood. In the past, it has been suggested that intestinal microbiota can affect the phenotype and function of immune responses through the dissemination of bacterial products or metabolites. Bacterial metabolites can directly act also on nervous system cells such as neurons, microglia, and astrocytes, impacting even on the quality of life. These evidences suggest that the microbiota can favor the appropriate education of the host immune system that might protect from the development of several diseases, included neurological disorders. However, there is still lack of mechanistic insight into how microbes could have a real beneficial role in the CNS development and function.