Gut microbiota is a complex system of microorganisms which colonize our gastrointestinal system. Overall, it is composed of viruses, bacteria, yeasts and protozoa, all living (hopefully) in relative harmony. Gut microbiota composition may vary among healthy and unhealthy individuals. In healthy subjects, gut microbiota live in good balance (eubiosis), meaning maintaining diversity, richness and relative abundance. In this way, gut microbiota and host co-exist in a cooperative systemic aggregation model, both contributing to regulation of the barrier effect, metabolism, immunocompetence and tolerance and influencing synthesis of many substances including neurotransmitters, drug metabolism and even behavior conditioning.

However, many factors such as massive use of antibiotics, the prolonged use of drugs that inhibit gastric acid production. .Besides others, proton pump inhibitors, and especially diet are able to alter eubiosis leading to a pathological condition called dysbiosis. Dysbiosis is a microbiota imbalance which in turn is strongly related to the occurrence of many diseases, including neurological disorders.

A healthy and balanced gut microbiota can reduce the risk of brain disease. The three most important effects are :

  • They help to control  inflammation.  A healthy microbiota can  limit the production of inflammatory chemicals in the body and in the brain. Inflammation, as you already know, is the basis for degenerative diseases.
  • They bolster the intestinal wall’s integrity and prevent high “leaky gut”. When the gut permeability is high, many proteins are able to cross the gut wall and challenge the immune system. This scenario turns on an immune response that also leads to inflammation and to a “leaky brain-blood-barrier”.
  • They produce important chemicals for brain health, including BDNF, vitamin B12 and neurotransmitters like glutamate and GABA.

The Gut-Brain-Axis

The brain-gut axis reflects the constant communication between the central nervous system (CNS) and the gastrointestinal tract. There is also a growing body of evidence that the intestinal microbiota influences the brain-gut interactions in different points of time (from early life to neurodegeneration), so the term microbiota-gut-brain axis has been proposed.

The communication between gut and brain occurs via:

  • Vagus nerve – directly connects the gut to the brain and sends signals in both directions. It plays a special role in stress response
  • Neurotransmitters – chemical substances act as messengers carrying information from one neuron to another. They can alter the functions of the central nervous system (CNS) and influence emotions. Many of these neurotransmitters are also produced by your gut cells and microbiota. A large proportion of serotonin, for instance, is produced in the gut.
  • Short-chain fatty acids (SCFA) – our microbiota is able to produce chemicals that affect how the brain works. SCFA, such as butyrate, propionate and acetate are important to control food intake, to the integrity of blood-brain-barrier and to control stress. In addition, they form an alternative fuel for all cells, especially brain cells.
  • Immune response – gut and brain are also connected through the immune system. Gut immune response or inflammation can lead to gut leakage and systemic inflammatory response as well as brain disorders.

Through all these pathways, gut microbiota exerts a widespread influence on key neurological and behavioral processes. Aging is associated with alterations in intestinal microbiota composition, structure and function, which plays an important role in the development of neurodegenerative diseases.

The Gut Brain Axis – Messages and Systems

Fig. 1: The Gut Brain Axis – Messages and Systems

Gut microbiome and Alzheimer’s disease

In AD patients, a clear decreased microbial richness and diversity is observed. They also present a distinct composition in gut microbiota compared to asymptomatic age- and sex-matched individuals. It has been proposed that these broad-scale changes (dysbiosis) may play important roles in disease progression, potentially through immune activation and systemic inflammation.

The main microbiota changes observed in AD patients are:

  • A decrease in the phylum Firmicutes
  • An increase in the phylum Bacteroidetes ( Gram negative bacterias, rich in LSP-lipopolysaccharide)
  • Decreased number of Bifidobacterium (anti-inflammatory bacterias)
  • A decrease in Akkermansia (also reduced in Diabetes type 2)
  • Increased abundance of the pro-inflammatory bacteria Escherichia/Shigella

Neuroinflammation is a key feature in the physiopathology of AD.  An inflammatory trigger can lead to microglia (brain defence cells) activation and neuroinflammation. In a chronic inflammation scenario, a self-perpetuating cycle of inflammation takes place and the result is diffuse amyloid deposits and neurodegeneration. Please refer to the Causes section to learn more.

In humans, intestinal permeability increases with age, leading to hyperstimulation of the immune system, elevations in peripheral pro-inflammatory cytokines and a constant state of low-grade inflammation, also known as “inflamm-aging”.

Alterations in gut microbiota composition together with the increase in intestinal permeability observed with age lead to the translocation of microbes or microbial components (like lipopolysaccharide -LPS) from the gut and induce systemic and CNS inflammation.

Promising preclinical and clinical data suggest that the modulation of gut microbiota through dietary ingredients or probiotics may provide a means to counteract the development or progression of neurodegenerative disease (you can find a list with clinical trials at Alzheimer’s Research section).

For more information, you can consult the Fact Sheet Dementia and Intestinal Health provided by the Academy of Human Medicine. You can find this in our download section.

References:

  1. Calvani R, Picca A, Lo Monaco MR, Landi F, Bernabei R, Marzetti E. Of Microbes and Minds: A Narrative Review on the Second Brain Aging. Front Med (Lausanne). 2018;5:53.
  2. Vogt NM, Kerby RL, Dill-McFarland KA, et al. Gut microbiome alterations in Alzheimer’s disease. Sci Rep. 2017;7(1):13537.
  3. Zhuang ZQ, Shen LL, Li WW, et al. Gut Microbiota is Altered in Patients with Alzheimer’s Disease. J Alzheimers Dis. 2018;63(4):1337‐1346.
  4. Kowalski K, Mulak A. Brain-Gut-Microbiota Axis in Alzheimer’s Disease. J Neurogastroenterol Motil. 2019;25(1):48‐60.
  5. Markowiak P & Śliżewska K: Effects of Probiotics, Prebiotics, and Synbiotics on Human Health.Nutrients. 2017 Sep; 9(9): 1021
  6. (2015). Brain maker: The power of gut microbes to heal and protect your brain–for life. New York: Little, Brown and Company. Perlmutter, David, and Kristin Loberg.