While the microbiome contains many different species of bacteria, why certain combinations of bacteria influence brain function and alter host physiology remains a head scratcher for researchers. To explore this phenomenon, researchers at the Champalimaud Center for the Unknown in Lisbon-Portugal ran several experiments to determine how the microbiome might affect the behavior of its host.
The study, published in the journal Nature Communications, studied fruit flies to determine whether two gut bacteria establish a metabolic cross-feeding that allows them to grow in diets that lack the essential nutrients as well as change host decision making and reproduction behaviors.
The authors acknowledged this would be no easy feat: "To study how bacteria affect their host physiology is a daunting task in organisms with very complex microbiomes. This is where the fly and its less complex microbiome emerges as a powerful tool. It allows us to precisely dissect the mechanisms used by the microbiota to change the host's feeding decisions," explained Sílvia Henriques, post-doctoral researcher and study author.
The authors also noted that the methodologies used in study will allow researchers to understand the precise mechanisms responsible for altering what animals decide to eat and brain function.
In a previous study researchers at the center found that the microbiome plays an important role in dictating how amino acids affect the brain. However, bacteria only affected the decisions of the animal when specific bacterial combinations were present.
The preceding study raised flies in a sterile environment and fed them a controlled diet. When the flies were deprived of single essential amino acids, they developed a hankering for protein-rich foods. However, it was observed that flies preferred sugar when associated with Acetobacter pomorum and Lactobacillus plantarum bacteria.
"Interestingly, the association of flies with any of these bacteria alone could not reduce yeast appetite. Thus, in this new study, our main focus was to understand why these two particular bacteria need to be present to change the feeding behavior of the fly," Carlos Ribeiro, principal investigator and senior author of the studies.
The research team observed the eating habits of the flies by using the flyPAD, a high-tech sensor developed in Ribeiro’s lab. The flyPAD technology allowed the scientists to precisely measure the feeding pattern of tiny, individual flies.
Using bacterial mutants, the team then examined how specific functions of the bacterial cells impacted behavior of the host. In collaboration with the University of Glasgow, they also used isotope-resolved metabolomics, a complex technique that allowed them to trace the metabolites that were exchanged between the two different bacteria.
Results: Microbes tell flies what to eat
"We found that the two bacteria exchange metabolites, and that this cross-feeding (syntrophy) enables them to grow and act on the animal even if diets lack the nutrients that are essential for them. Specifically, we now understand that Lactobacillus strains produce lactate, which is used by the Acetobacter strains to synthesize amino acids and other metabolites. These are then used by the Lactobacillus strain which cannot synthesize them to continue to produce lactate. Furthermore, these bacterial amino acids are very likely used by the animal for egg production. But most importantly, we now understand that the lactate is also used by the Acetobacter bacteria to change the behavior of the fly," explained Darshan Dhakan, post-doctoral researcher and author.
“By combining the right technologies with the right experimental system we can get at the heart of the mechanisms by which the microbiome interacts with our diet to affect our brain and our body,” said Ribeiro. “Importantly, we show that the right associations of bacteria can make the microbiome resilient to dietary perturbations, explaining why some animals and people might be more sensitive to the nutrient content of food than others. It is also a beautiful example of how nature establishes circular economies where nothing gets wasted and everybody gains."
“Those insights can then be used to guide the search for similar mechanisms in animals with much more complex microbiomes, including in humans," concluded Ribeiro.
Source: Nature Communications
“Metabolic cross-feeding in imbalanced diets allows gut microbes to improve reproduction and alter host behavior”
11, 4236 2020 DOI: 10.1038/s41467-020-18049-9
Authors: S. Henriques et al.