COMMENTARY

The Microbiome and Brain Health: What's the Connection?

Sarah R. Dash

Disclosures

March 24, 2015

In This Article

Introduction

Researchers are now beginning to understand the ways in which bacteria living in the human gut—the gut microbiota—communicate with and influence brain health. The concept of a faulty "gut/brain axis" has been associated with various neurologic and psychiatric outcomes and is thought to be explained, at least in part, by immune dysfunction and inflammation triggered by poor gut health.[1]

The gut microbiota has emerged as an important focus in the understanding of noncommunicable diseases, including type 2 diabetes and cardiovascular disease, as well as disorders of the brain. Brain-related conditions place a great burden on society, and the limitations of current interventions reflects the need for ongoing investigations into understanding and treating brain disorders, in part by exploring the close relationship between our biome and our brain.

Biome and Brain Overview

The human intestinal microbiome is seeded at birth; it is influenced initially by delivery and feeding mode, and reaches an adult-like state within the first few years of life.[2] Alterations in the composition, diversity, and stability of gut microbiota have been linked to a broad range of diseases, including autoimmune, metabolic, gastrointestinal, and brain disorders.[3,4]

Although the composition of the gut microbiota remains relatively stable during our middle years, it continues to be influenced by such factors as geography, antibiotics, exercise, and diet. This is particularly important when considering possible prevention and intervention in brain disorders.

It is well known that bidirectional gut/brain communication may occur directly and indirectly via the central and enteric nervous systems, the vagus nerve, and the endocrine and immunoinflammatory systems and through the modulation of neurotransmitters.[1] Diet could also utilize these pathways, because the gut microbiota supports optimal nutritional bioavailability—for example, by maintaining normal plasma tryptophan levels, an important building block for making serotonin, a key central nervous system neurotransmitter.[1] Advances in this field have come from the development of DNA sequencing technology, which allows researchers to conduct large-scale screening of the bacteria in the gut and their associated physiologic functions. This has helped researchers to link disruption of the gut microbiota with biological markers of the communication pathways mentioned above.

It is important to note that there is so far no "gold standard" healthy intestinal microbial profile. Genetic and environmental factors mean that there may be significant variability in gut composition from person to person. In general, a "healthy," diverse gut microbiota promotes gut health and maintains essential structural, metabolic and signaling functions. The human gut can be "unhealthy" for a variety of reasons. Typically, a shift away from normal gut microbiota diversity and stability—termed "dysbiosis"—means it is unable to sustain one or more of the functions of a healthy gut, and this may contribute to metabolic, autoimmune, and brain disorders.

Increased intestinal permeability, often called "leaky gut," occurs when the mucosal gut barrier fails to prevent potentially harmful molecules from entering the bloodstream; these molecules include lipopolysaccharides, which are found on the outer membrane of gram-negative bacteria and may elicit inflammatory responses in the body.[5] Increased intestinal permeability is a common feature of an unhealthy gut.

Keeping in mind that each gut microbiome looks different, the terms "healthy" and "unhealthy" used here refer to instances in which gut microbiota functioning, composition, or ratio may deviate from a person's individual-specific "normal" state.

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