Microbial colonization in sea anemones used to understand transcriptomic response to drugs, researchers find

23 Nov 2023 --- A German research team headed by Heinrich Heine University Düsseldorf (HHU) has investigated the intestinal functioning of a sea anemone — Nematostella vectensis or cnidaria — to see how the microbiome develops with its host and established that the degradation of the polysaccharide chitin plays a central role for the initial colonizers. Initial colonization with the right microbes can illuminate ways to train the adaptive immune systems of humans from birth onward.

Nematostella’s production of chitin was only recently discovered, although its reason is still unknown. These creatures do not need the chitin for their structural development like insects. Fraune says: “Our results indicate that chitin plays a role in the microbiome.”

“It is a highly researched field to understand how in humans the exposure to specific bacteria during early life can have long-term effects on the microbiome composition and on the health of adults,” Dr. Sebastian Fraune, professor at the Institute of Zoology and Organismic Interactions at HHU and head of the study, tells Nutrition Insight.

“These studies often include the development of the adaptive immune system in dependence of microbe exposure. However, as cnidarians don’t possess an adaptive immune system, they can help to understand the mechanisms of microbial colonization, which are independent of the adaptive immune system but on the innate immune system or nutrient availability.”

“As babies don’t have a fully functioning adaptive immune system yet, experiments in invertebrates could shed more light on the early recolonization of humans,” Fraune notes.

Sea anemone’s immune story 
In their research, which was published in Microbiome, the authors describe that the host organism controls the bacterial community during the early stages of life, while bacteria-bacteria interactions play the lead role in subsequent development.

The sea anemone only has an innate immune system, but its microbiome’s mysteries and scientific findings are relevant for medical research. Newborn babies, for example, have an innate immune system at birth and come into contact with numerous bacteria immediately after birth. 

This is where the benefits of “initial colonization” come into play because colonization with the right microbes can unlock information to create a functioning microbiome and train the adaptive immune system in humans.

“It is important to study models to understand the mechanisms of microbial colonization and selection during early life. In this study, we show the host’s transcriptomic response to recolonization with its microbiome, therefore identifying several genes important in microbiome selection,” Fraune explains.

“We also show the bacterial metabolic potential during the recolonization, therefore identifying several processes which could explain a bacterial succession during the recolonization.” 

Disrupted microbial colonization during the early development phase changes metabolic and immune programming and appears to be connected with an increased risk of immune system and metabolic disorders. According to Fraune, initial studies are being conducted where children born by Cesarean section are brought into contact with the vaginal secretions of the mother immediately after birth to ensure natural initial colonization.Microbial colonization has been further explored to find out more about the impact of early colonization of health later in life.

“As for recolonization, we have transcriptomic data of the host and metabolic potential data of the bacteria; it is possible to link the host’s to the bacterial reaction during the recolonization process, which gives us the opportunity to unveil a host-bacterial interplay,” he says.

“It is now important for future research to investigate this interaction in more detail. For example, we want to investigate whether disturbing this interaction leads to an impairment of colonization with long-term effects on the host.”

Initial colonization and recolonization
The current study’s researchers analyzed three cases to see how the microbiome develops over time. They discovered that only the initial colonizers, i.e., the bacteria forming the youngest animals’ microbiome, became well-established in the adult polyps. By contrast, it was difficult for the bacteria from older animals to become established.

“Following recolonization, the microbiome undergoes a process very similar to the normal development of host and microbiome. It takes around four weeks to reach the same status as adult animals that have undergone a normal growth process,” says Fraune. From this, the researchers deduce that the host controls the composition of the original colony. 

“However, the host no longer has a significant influence over the further development of the microbiome after this point. The bacteria control this themselves and lay suitable foundations for their descendants,” says Dr. Hanna Domin, lead author of the study.

Seeking answers
The pertinent questions the German researchers wanted to answer were how the microbiome develops as the host develops; which factors determine how it changes as the host matures; does the host control colonization with the right microbes, or do the microbes regulate themselves? 

Research has already established that the composition and ratio of the microorganisms in the sea anemone differ fundamentally between the different stages in its life cycle and only assume a stable form in the adult anemone. 

Domin explains: “We took adult Nematostella polyps, which had no microbiome following intensive antibiotic treatment and then recolonized them in a targeted way. To do this, we used bacterial communities that corresponded to those of firstly a Nematostella larva, secondly a juvenile animal and thirdly an adult polyp.”

An essential aspect of the research was to examine metabolic networks and investigate how the different bacteria are linked via their metabolism and influence each other. “We were able to identify metabolic pathways, which are specific to the initial colonizers, as well as pathways that only play a role at a later stage,” says Dr. Johannes Zimmermann from Kiel University (CAU).

The research was conducted within the Collaborative Research Centre1182 “Origin and Function of Metaorganisms” framework, headed by CAU.

Meanwhile, nutrition brands highlight a sustained demand for products targeting the gut-brain axis as research builds a better understanding of the links between the intestinal microflora and other health areas. 

By Inga de Jong