Foundation-Funded Research Connects Bacteria in Digestive Tract with Infant, Lifelong Mental Health

Gerard Clarke, Ph.D. - Brain and behavior research expert on anxiety
Gerard Clarke, Ph.D.

In recent years, scientific literature has exploded with articles about the role of the enormous population of bacteria that colonize the gastrointestinal tract. In two recently published papers, 2013 NARSAD Young Investigator Grantee Gerard Clarke, Ph.D., Lecturer in the Department of Psychiatry at University College Cork in Ireland, used his NARSAD Grant to examine evidence suggesting fundamental links between gut bacteria, brain function and mental health. More specifically, he sought to understand this interplay (what he calls “the microbiome-gut-brain axis”) and how it may be a target for the treatment of anxiety disorders.

Dr. Clarke anticipates “that the results of this project will hasten the considerable promise shown by this exciting new research avenue, with the accrual of benefits at the preventative, diagnostic and therapeutic levels.” He goes on to note that “the NIMH [National Institute of Mental Health] states that understanding how differences in microbiota profiles influence the development of brain and behavior will be one of the great frontiers of clinical neuroscience in the next decade.”

Gut bacteria “produce numerous hormonal chemicals which are released into the bloodstream” and act at sites throughout the body, “including the brain,” Dr. Clarke and colleagues report in a paper published online in Molecular Endocrinology on June 3rd. Studies conducted with animals, such as rodents, raised in a germ-free environment have shown an exaggerated response to stress, which can be normalized when certain bacterial species are allowed to colonize the intestinal tracts of such animals. In this current project, the researchers worked with conventionally colonised, germ-free and colonised germ-free animals. They used sophisticated genetic sequencing methods to examine if and how gut “microbiota” affect the central nervous system and report that they have, for the first time to their knowledge, established that the genetic influence of the gut microbiota extends to microRNA (microRNA regulate how genes are expressed) expression in the central nervous system.

A second paper, appearing May 17th in Acta Paediatrica, and co-authored by Dr. Clarke, examines how gut microbes acquired early in life regulate the brain and behavior throughout life. The infant gut is rapidly changing in the first three years of life, related to major epochs in the pre- and neonatal period. These include the period before birth, in which it was once thought the fetus developed under sterile conditions. There is emerging evidence that suggests this may not be true. Whether the womb is sterile or not, it is now beyond question that different populations of bacteria colonize the infant gut at and after birth.

The researchers report that they found that “the absence of microbiota (i.e., bacteria) in early life reduces anxiety-like behaviors in adult mice.” These proof-of-principle studies are borne out by interventions later in life that modulate the gut microbiota, such as probiotic and antibiotics, which can also influence the expression of anxiety-related behavioral phenotypes.   

For now, they say, the most important research findings are those that establish a link between the three-year period at the start of life when the gut is colonized and critical periods in human development in which the central nervous system and brain are undergoing rapid growth.

Read the abstract from Molecular Endocrinology.

Read the abstract from Acta Paediatrica.