A study using Pavlovian threat and extinction conditioning reported that gut microbiota composition was associated with how quickly a person learned threat reactions in the scope of the procedure, but not with how quickly the threat reaction was extinguished. The study was published in PNAS Nexus.
Learning about threats and safety is critical for survival. Studies conducted on rodents have demonstrated that gut microbiota can modulate these behaviors. Gut microbiota is the collective of trillions of microorganisms, mainly bacteria, living in our large intestines. These microorganisms play a key role in digesting the food we eat. They help in absorbing nutrients, but also in synthesizing them.
Recent studies have uncovered the existence of a communication pathway that connects the gut microbiota with the brain. This pathway is known as the microbiota-gut-brain axis. It is based on small proteins called cytokines and a number of other molecules. These include the hormone cortisol, short-chain fatty acids, tryptophan and others.
Gut microbiota has been shown to modulate anxiety-like behavior in rodents, but also learning that depends on the hippocampus and amygdala regions of the brain. In experiments, rodents treated with probiotics showed better memory and decreased anxiety-like behaviors compared to untreated rodents and rodents without gut microbiota.
In humans, the ability to learn about threats is known to be related to anxiety. Given the findings about relationships between anxiety and gut microbiota in rodents, study author Javiera P. Oyarzun and his colleagues wanted to explore whether threat learning might be related to the gut microbiota composition in humans i.e., to the concentrations of various microorganisms in the human gut.
Study participants were 127 healthy individuals recruited from the New York University community. Seventy-three participants were female. The average age of participants was 27 years. Participants were required to be proficient in English, have normal or corrected vision, have no medical disorders and not be taking any psychoactive medications, corticosteroids, antibiotics or probiotics.
In the course of the experiment, each participant had two electrodes connected to the wrist of his/her dominant hand and another set of electrodes connected to the non-dominant hand. The purpose of the first pair of electrodes was to deliver electric shocks i.e., cause pain to the participant, while the other set of electrodes measured skin conductance response, i.e., a physiological indicator of the participant’s emotional reaction (fear). The participant was then presented with two black-and-white images of human faces with fearful expressions in sequences, one image at a time, multiple times.
Participants were informed that one of the pictures will be followed by an electric shock to the wrist delivered through the electrodes, while the other one will never be followed by a shock. They were not told which of the two pictures will be paired with a shock. Researchers recorded how quickly the participant learned to react with increased skin conductance to the picture associated with the shock i.e., manifest the so-called threat response. This was the threat learning procedure.
After this, participants went through extinction and recovery sessions, the goal of which was to extinguish the threat response to the picture that was associated with shocks in the previous session. This was done by showing the participants the pictures (in sequences, one at a time, multiple times), but without delivering electric shocks. Researchers recorded how quickly participants lost the threat response. They then calculated the association between the rates at which different participants learned the threat response and lost it with concentrations of certain species of microorganisms in their guts.
The procedure was conducted over two days. After the first day or the next morning, participants gave stool samples. Researchers conducted genetic analysis of these samples to obtain data on the concentrations of different species of microorganisms in the participants’ guts. These different species constituted the gut microbiota.
Results showed that participants who learned the threat response at different rates also showed different patterns of gut microbiota composition. Three groups of microorganisms were related with how quickly participants learned the threat response – UBA1819 (an unclassified Faecalibacterium taxon), Tyzzerela_3, and Bacteroides. However, further analysis showed that these associations were likely driven by individual participants with extreme values, so-called outliers.
Due to this, study authors looked for communities of microorganisms associated with these responses. This analysis identified groups of microorganism species (taxa) that were associated with learning the threat response. The 8 most important turned out to be Butyricicoccus, Agathobacter, Alistipes, Phocea, and Veillonella, in addition to the three groups already mentioned.
“The present study found that gut microbiota composition in humans is associated with threat acquisition and excitatory learning using two omnibus microbiome analysis techniques, which controlled for confounding factors associated with microbiota composition (age, gender, BMI, human milk feeding versus formula, mode of birth, exercise, current pet cohabitation, childhood pet cohabitation, and diet),” the researchers wrote.
“The associations found in our dataset may rely on microbial chemical products or functions shared by multiple taxa or external influences that affect both the microbiome and the threat acquisition.”
The study sheds light on possible wider effects of the gut microbiota. However, it also has limitations that need to be taken into account. Notably, the study design does not allow any cause-and-effect conclusions to be drawn. Additionally, the number of study participant might have been too small to detect all the effects researchers were looking for.
The study, “Human threat learning is associated with gut microbiota composition”, was authored by Javiera P. Oyarzun, Thomas M. Kuntzc, Yoann Stussia, Olivia T. Karamana, Sophia Vranosa, Bridget L. Callaghand, Curtis Huttenhower, Joseph E. LeDoux, and Elizabeth A. Phelps.
