Harvard Medical School team leads pioneering gut-brain research

Original article posted Oct 12, 2018

You are not alone — literally. And in a way, you are also not entirely 100 percent human — from a cellular perspective. According to the National Human Genome Research Institute, the human body is host to approximately 10 times as many non-human microbial cells to human cells [1]. There are 10-100 trillion microbiota (microbes) that live inside and outside the human body [2]. The human microbiota includes fungi, protozoa, bacteriophage, yeasts, single-cell eukaryotes, viruses, and bacteria. The genes of the human microbiota make up the human microbiome. What influence, if any, does the microbiome have on the brain and behavior? In a landmark 2018 study published in Molecular Psychiatry, a team of researchers from Harvard Medical School, the Broad Institute of MIT and Harvard, and the University of Toyama, found that “changes in gut microbiota can control brain insulin signaling and metabolite levels,” which in turn impacts neurobehaviors [3]. In the research study, the scientists discovered that mice fed a diet high in fat expressed increased depressionanxiety, and obsessive-type behaviors, compared to those on a standard diet [4]. The mice with diet-induced obesity exhibited insulin resistance in the brain [5]. The researchers attributed the increased behaviors that reflect anxiety and depression to “decreased insulin signaling and increased inflammation in the nucleus accumbens and amygdala. [6]” The scientists then altered the microbiome of the obese mice with antibiotic treatment. The results were improved insulin sensitivity (both peripheral and central), and the reversing of the behavioral and mood disorders [7]. The researchers then transferred the microbiota from the obese mice that received antibiotics and those that did not, to germ-free mice that lack a natural microbiome. Only the germ-free mice that received the microbiota from the obese mice that did not receive antibiotics started to exhibit signs of increased anxiety and obsessive behaviors — leading the research team to conclude that the gut microbiome was a contributing factor [8]. The scientists believe that unlocking the gut-brain relationship “may open novel approaches to treatment of mood and behavioral disorders" in the future. Grant 1353571; CCF-1231216), the McDonnell Foundation, the Howard Hughes Medical Institute. NINDS is the nation’s leading funder of research on the brain and nervous system. The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease. About the National Eye Institute (NEI): NEI leads the federal government’s research on the visual system and eye diseases. NEI supports basic and clinical science programs to develop sight-saving treatments and address special needs of people with vision loss. For more information, visit https://www.nei.nih.gov. About the National Institute of Mental Health (NIMH): The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website. About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.


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