The Gut-Brain Axis: Part 1 of 3

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The Gut-Brain Axis: Part 1of 3

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We each have a unique and complex network of microbes living within our guts known as a
microbiome. It is comprised of a dynamic ecosystem of viruses, fungi, and predominately
bacteria. As humans, we have been evolving and diversifying in concert with our microbiomes
for at least 15 million years, indicating a close bacteria-host mutualism. Colonization of your gut
microbiome occurs during birth, is highly dynamic throughout infancy, and resembles adult
microbiomes in approximately three years remaining stable thereafter. Several factors influence
the microbiome, such as genetics, diet, metabolism, age, geography, stress, antibiotic treatment,
probiotics, disease, and more. Microbes within the microbiome are responsible for extracting
energy from the food we eat, vitamin biosynthesis, pathogen overgrowth protection, educating
our immune system, and more.

Alterations in the gut microbiome are associated with an array of metabolic and gastrointestinal
diseases like irritable bowel syndrome (IBS) and insulin resistance, but recent research has found that other body regions are also affected. Your gut microbiome is important and key in regulating digestion, hormones, immunity, the brain and cognition. Due to this newly established relationship between the central nervous system (CNS) and our gut microbiomes a circular communication loop, often referred to as the gut-brain axis, has been established. The loop is bidirectional with disruption at one end of the axis often instigating a dysregulation in the other. Changes to the gut microbiome have recently been associated with neurodegenerative diseases like Parkinson’s disease, multiple sclerosis, and Alzheimer’s disease (AD).

Recent studies performed in mice suggest that alterations in the gut microbiome contribute to
amyloid plaque deposition in AD. AD mice treated with long-term broad-spectrum antibiotics (to
significantly alter their microbiome population) result in less amyloid plaque deposition with
higher circulating soluble amyloid levels compared to untreated AD mice. Analyses of the AD
mouse microbiome revealed decreased microbial diversity in treated mice with reduced
Firmicutes and Bifidobacterium bacteria, but increased Bacteroidetes bacteria compared to
untreated mice. Additionally, although the balance of microbiome components changed, the total abundance of the population remained similar to pre-antibiotic treatment. These findings suggest that the gut microbiome diversity plays a role in regulating individual amyloid plaque
development, or amyloidosis.

Based on animal studies, diet and physical exercise also effect the gut microbiome resulting in
further downstream effects on cognition. Mice consuming a high fat diet (HFD) compared to a
normal diet (ND) restructure their gut microbiomes resulting in increased anxiety. Exercise was
shown to alter the microbiomes of both groups to similar magnitudes regardless of diet. Although exercise slightly improved memory in HFD mice, it could not quell their
increased anxiety, indicating that exercise cannot counteract all effects of a poor diet. Exercised
ND mice show increased memory and learning and result in increased Firmicutes bacterial
strains when compared to ND mice without exercise. Diets high in fat and exercise both have the ability to alter the gut microbiome and behavior, but independently.

Mice with reduced microbiomes from birth result in modified development of two particular
brain regions, the amygdala and hippocampus. Signaling between the amygdala and hippocampus modulates social behaviors and anxiety, and alterations in their development may
lead to disrupted behaviors. Both regions enlarged in germ free (GF) mice, but total brain
volume remained similar to normal germ (NG) mice. The amygdala appeared to be hyperactive
in GF mice with an underactive hippocampus compared to NG mice. GF mice have an increased
stress response compared to NG mice. This research indicates that an appropriately populated
microbiome is necessary for normal brain development and neural communication and might
prevent the development of mental illness like depression and anxiety.

The brains of animals with modified or absent microbiomes display a variety of molecular
differences, like varried expressions of neurotransmitters and their receptors when compared to
animals with unaltered microbiomes. Reductions in brain-derived neurotrophic factor (BDNF)
gene expression occurs in GF mice compared to NG mice, primarily in the hippocampus. BDNF
is important for neuronal survival and growth, and learning and memory. Inhibitory
neurotransmitter effects were lower in the hippocampus and amygdala of mice that ingested L.
rhamnosus bacteria as a probiotic compared to those untreated. These same mice display reduced anxiety- and depression-related behavior. This not only emphasizes that our microbiome effectsour cognition, but that we can purposefully manipulate it. If we can learn more about the gut-brain axis and determine which microbes are beneficial we could use them as viable treatments.

It’s becoming more and more clear that our microbiomes greatly influence our bodies, including
the brain, but what about the effects our brains may have on our microbiomes? Do we possess
the ability to modify our microbiomes to serve our bodies better? Tune in next week for part two
in the three part series that is: “The Gut-Brain Axis”!!

Sources: 
Bray, Natasha. “The Microbiota–Gut–Brain Axis.” Nature News, Nature Publishing Group, 17 June 2019, www.nature.com/articles/d42859-019-00021-3.
Kang1, Silvia S, et al. “Diet and Exercise Orthogonally Alter the Gut Microbiome and Reveal Independent Associations with Anxiety and Cognition.” Molecular Neurodegeneration, BioMed Central, 13 Sept. 2014, molecularneurodegeneration.biomedcentral.com/articles/10.1186/1750-1326-9-36.
Luczynski, Pauline, et al. “Adult Microbiota‐Deficient Mice Have Distinct Dendritic Morphological Changes: Differential Effects in the Amygdala and Hippocampus.” Wiley Online Library, John Wiley & Sons, Ltd (10.1111), 8 July 2016, onlinelibrary.wiley.com/doi/pdf/10.1111/ejn.13291%4010.1111/%28ISSN%291460-9568.british_neuroscience_association_festival_of_science2019.
Mayer, Emeran A., et al. “Gut/Brain Axis and the Microbiota.” The Journal of Clinical Investigation, American Society for Clinical Investigation, 2 Mar. 2015, www.jci.org/articles/view/76304.
Sarkar, Amar, et al. “The Microbiome in Psychology and Cognitive Neuroscience.” Trends in Cognitive Sciences, U.S. National Library of Medicine, July 2018, www.ncbi.nlm.nih.gov/pubmed/29907531.
Vogt, Nicholas M., et al. “Gut Microbiome Alterations in Alzheimer's Disease.” Nature News, Nature Publishing Group, 19 Oct. 2017, www.nature.com/articles/s41598-017-13601-y.