In recent years, there has been a groundswell of animal studies linking gut-brain-microbiota interactions with various social behaviors and mood disorders. However, until now, there has been a scarcity of human studies on the correlation between gut microbial composition and various behavioral and neurobiological differences in Homo sapiens.
This week, a pioneering new study from the University of California, Los Angeles (UCLA) identified specific ways that gut microbiota may interact with various brain regions to affect mood and behavior in healthy humans. The findings were published June 29 online ahead of print in Psychosomatic Medicine: Journal of Behavioral Medicine.
Microbiota is an ecological community of microorganisms that are generally a combination of both beneficial “good bacteria” and potentially harmful bacteria. The human gut harbors over 100 trillion microorganisms. This is approximately ten times the number of cells in the entire human body. Microbes begin residing within human intestines shortly after birth. Microbiota is vital to the healthy development of your immune system and is associated with various important neurobiological functions.
As mentioned earlier, previous animal studies on gut-brain-microbiota interactions using rodent and chimpanzee models have identified a link between gut microbiota, social behaviors, and well-being.
For example, in 2015, scientists from McMaster University reported that intestinal bacteria played a role in both anxiety and depression based on a mouse study, “Microbiota and Host Determinants of Behavioural Phenotype in Maternally Separated Mice,” published in the journal Nature Communications. In this study, researchers subjected mice to early life stress by separating newborns from their mother for three hours each day. Neonatal stress reactivity increased gut dysfunction as marked by changes in microbiota which, in turn, appeared to correlate with altered brain function as part of a bi-directional feedback loop.
As another example, a 2016 paper, “Social Behavior Shapes the Chimpanzee Pan-Microbiome,” published in Science Advances reported that having frequent social interactions promoted the richness and diversity of microbiomes needed for a chimp's optimal gut health.
For this study, researchers from Duke University monitored changes in the gut microbes and social behavior of wild chimpanzees over eight years in Gombe National Park, Tanzania. The scientists found that the quantity and variety of bacteria in the GI tract increased when the chimpanzees mingled and were more gregarious. Although spending time in close physical contact with other chimps increases exposure to germs, the researchers found that being sociable also increased the exposure and colonization of "good" gut bacteria.
Prior to the latest report by Kirsten Tillisch, associate professor of medicine in the Division of Digestive Diseases and colleagues at UCLA, there has been a lot of speculation, but very little empirical evidence on the brain-gut-microbiota interaction in humans—especially as it relates to the link between brain structure and responses to emotional stimuli.
For their recent study, Tillisch et al. wanted to identify brain and behavioral characteristics clustered by someone's gut microbiota profile. The researchers enlisted forty healthy women and divided them into two groups based on each person's gut bacteria composition. One group of 33 had more of a bacterium called Bacteroides, the remaining seven had more of the gut bacteria called Prevotella.
Then, the researchers conducted two different state-of-the-art brain imaging techniques. First, they used structural and diffusion tensor imaging (DTI) to obtain gray matter metrics (volume, cortical thickness, mean curvature, and surface area) as well as white matter fiber density connecting various brain regions. Second, they conducted fMRI brain scans to assess microbiota-based group differences in response to observing emotionally affective images.
White matter and gray matter imaging showed differences between the Bacteroides and Prevotella clusters. As an example, the Prevotella cluster displayed more robust white matter connectivity between emotional, attentional, and sensory processing brain regions. Regarding gray matter volumes, the Bacteroides cluster showed greater prominence in the cerebellum, frontal regions, and hippocampus.
Notably, the Prevotella group displayed more functional connectivity between emotional and attentional sensory brain regions combined with lower brain volumes in various brain regions including the hippocampus. Additionally, the Prevotella group showed less hippocampal activity while viewing emotionally negative valence images in the fMRI. This group also displayed higher levels of negative feelings such as anxiety, distress, and irritability after looking at photos with negative emotional valence images than the Bacteroides group.
There is one important caveat. Before drawing any firm conclusions based on these results, it's important to note that correlation does not necessarily mean causation. As the researchers' state in their conclusion: "These results support the concept of brain-gut-microbiota interactions in healthy humans. Further examination of the interaction between gut microbes, brain and affect in humans is needed to inform preclinical reports that microbial modulation may affect mood and behavior."
The new UCLA study identifies an association of brain-gut-microbiota interactions in healthy humans, but more research is needed. The million-dollar "chicken or the egg" question remains: Does gut microbiota directly influence changes in the brain or do changes in the brain influence the type of bacteria that reside in the gut? Also, how do various lifestyle, dietary, and environmental factors influence brain-gut-microbiota interactions in humans?
Although this research is in its early stages, the latest findings by Kirsten Tillisch and colleagues at UCLA present exciting possibilities. Hopefully, ongoing and future clinical studies aimed at better understanding the gut-brain-microbiota axis will result in novel approaches to the treatment and prevention of psychological disorders, including both anxiety and depression.
"Brain structure and response to emotional stimuli as related to gut microbial profiles in healthy women." Tillisch, Kirsten; Mayer, Emeran; Gupta, Arpana; Gill, Zafar; Brazeilles, Rémi; Le Nevé, Boris; van Hylckama Vlieg, Johan E.T.; Guyonnet, Denis; Derrien, Muriel; Labus, Jennifer S. Psychosomatic Medicine: Published online ahead-of-print June 29, 2017 DOI: 10.1097/PSY.0000000000000493
G. De Palma, P. Blennerhassett, J. Lu, Y. Deng, A. J. Park, W. Green, E. Denou, M. A. Silva, A. Santacruz, Y. Sanz, M. G. Surette, E. F. Verdu, S. M. Collins, P. Bercik. Microbiota and host determinants of behavioural phenotype in maternally separated mice. Nature Communications, 2015; 6: 7735 DOI: 10.1038/ncomms8735
A. H. Moeller, S. Foerster, M. L. Wilson, A. E. Pusey, B. H. Hahn, H. Ochman. Social behavior shapes the chimpanzee pan-microbiome. Science Advances, 2016; 2 (1): e1500997 DOI: 10.1126/sciadv.1500997
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