Gut bacteria influence the brain indirectly, study shows

A new study has found that there is a three-way relationship between a type of gut bacteria, cortisol, and brain metabolites. This relationship, the researchers hypothesize, may potentially lead to further insight into autism, but more in-depth studies are needed.

Research previously covered by Medical News Today suggested that there might be a link between bacteria found in the gut and the development of autistic behavior. Recent studies continue to establish links between the gut microbiome and autism spectrum disorders (ASD).

However, the exact way in which gut microbes might influence brain development is still subject to debates and further studies.

Now, researchers from the University of Illinois at Urbana-Champaign have found that there may be a three-way mechanism of communication between gut microbes and brain metabolites, involving cortisol as the channel through which the "message" is transmitted.

First study author Austin Mudd, a doctoral student at the University of Illinois, explains that brain metabolites can have a strong impact on the development of infants, and that these could be influenced by the gut microbiome.

"Changes in neurometabolites during infancy can have profound effects on brain development, and it is possible that the microbiome - or collection of bacteria, fungi, and viruses inhabiting our gut - plays a role in this process," he says.

It was this mysterious interaction between the brain and the gut that motivated the researchers to investigate the mechanism at play. The researchers' findings were published in the journal Gut Microbes and are available online.

Gut bacteria predict brain metabolites

In this study, the scientists used 1-month-old piglets, since they are the animals with most similarities to human infants when it comes to the development of the brain and the gut microbiome.

"Using the piglet as a translatable animal model for human infants provides a unique opportunity for studying aspects of development which are sometimes more difficult or ethically challenging to collect data on in human infants," explains Mudd.

"For example, in this study we wanted to see if we could find bacteria in the feces of piglets that might predict concentrations of compounds in the blood and brain, both of which are more difficult to characterize in infants," he adds.

First, the researchers found that the Bacteroides and Clostridium bacteria, identified in the animals' feces, predicted higher levels of myo-inositol, which is a substance that plays a role in cell signaling. Bacteroides could also predict higher quantities of creatine - an amino acid-like compound - in the brain.

The scientists also noticed that Butyricimonas bacteria could positively predict n-acetylaspartate (NAA), an amino acid found in the brain. At the same time, they found that an abundance of Ruminococcus bacteria in the feces correlated with lower concentrations of NAA in the brain.

Mudd highlights the fact that previous research had already suggested a link between abnormal NAA and the development of ASD, but so far, nothing had led scientists to note correlations between gut bacteria and NAA.

"These brain metabolites have been found in altered states in individuals diagnosed with autism spectrum disorder [...], yet no previous studies have identified specific links between bacterial genera and these particular metabolites."

Austin Mudd

Cortisol acts as communication channel

Next, the researchers sought to establish whether these types of bacteria could also predict the concentration of certain compounds in the blood.

Study co-author Ryan Dilger, who is an associate professor at the University of Illinois, explains that collecting fecal samples and blood biomarkers from infants would be more feasible than carrying out other tests. If this approach is proven effective, it would enable easier tests that could flag up potential ASD predictors.

"Blood biomarkers are something we can actually collect from an infant, so it's a clinically relevant sample. It would be nice to study an infant's brain directly, but imaging infants is logistically and ethically difficult. We can, however, obtain feces and blood from infants," says Prof. Dilger.

It was found that the microbes from feces could predict levels of serotonin and cortisol, both of which are influenced by gut bacteria. Bacteroides bacteria were linked with higher levels of serotonin, and abundant Ruminococcus were associated with lower levels of both compounds.

The study authors note that their findings support the results of existing studies that separately observed the associations between ASD and altered levels of serotonin and cortisol, on the one hand, and an abundance of Bacteroides and Ruminococcus in the feces, on the other.

Using "mediation analysis," a statistical method, the researchers tested the existence of a three-way relationship between Ruminococcus, NAA, and cortisol.

They found that cortisol in the blood acted as a sort of "channel of communication" between fecal Ruminococcus and cerebral levels of NAA. This suggests that Ruminococcus influence changes in the brain indirectly, through serum cortisol.

The researchers conjecture that this three-way mechanism could play a role in determining ASD symptoms, but they caution that this must be confirmed by further in-depth studies.

"We remain cautious and do not want to overstate our findings without support from clinical intervention trials, but we hypothesize that this could be a contributing factor to autism's heterogenous symptoms," says Mudd.