Hydrogen-Rich Water in Older Adults
October 31, 2021The Role of Phytochemicals in Health
November 19, 2021The Gut Microbiota: Its Key Features and Implications for the Function of the Central Nervous System
What is the gut microbiota?
Gut microbiota is the complex entity of microorganisms (organisms that can be visualized only under a microscope) inhabiting the digestive tract and especially the colon (the longest section of the large intestine). Amazingly, there are approximately 100 trillion microorganisms in the gut of each human being creating a unique microbial environment.1 These microorganisms are representatives of about 5,000 species, and altogether they weigh approximately 2 kg.1 Other human organs, such as the nasal cavity, oral cavity, skin, and distal part of the urethra also contain microorganisms,2 but the gut microbiota is especially diverse. Researchers are working actively on identifying the microorganisms that constitute the gut microbiota in healthy individuals and establishing their physiological role.2 Moreover, the association of the microbiota composition with a number of medical conditions is being investigated. Interestingly, the gut microbiota has important functions in healthy individuals, and certain constellations of the gut microbiota have been implicated in different disorders.1
How is the gut microbiota regulated?
The regulation of the gut microbiota is complex. It has been demonstrated that microorganisms start colonizing in the digestive tract of a fetus, and that the microbiota is transmitted to the fetus by the mother.3 The manner of birth itself can influence the gut microbiota because there have been differences observed between the gut microbiota of babies born by Cesarean section and babies born by vaginal birth.4 Notably, the genetic build-up of an individual influences the composition of the gut microbiota.5 It has been estimated that the gut microbiota of children starts to resemble the one of adults at around 3 years of age. The composition of the gut microbiota is unique to each individual and is mainly considered stable even though fluctuations may occur under the influence of environmental factors. Thus, dietary factors have been associated with temporary changes in the gut microbiota, however, whether these changes can be sustained long term is a question that should be investigated in studies with long follow-up periods.6 Other factors commonly investigated for their potential effects on the gut microbiota include stress and exercise. Also, certain medications may also interact with the gut microbiota in a bidirectional manner, whereby the drugs may affect the microbiota composition, and the microbiota may influence the action of some drugs.7
How is the gut microbiota implicated in human health and disease?
The gut microbiota has been implicated in many biological processes occurring in healthy people. For example, the healthy composition of the gut microbiota is important for the digestion of food and absorption of nutrients (substances providing nourishment) in the intestine. Moreover, the gut microbiota is involved in the production of important metabolites (substances formed as a result of the biological processes occurring in the body). Notably, the microbiota is also very important for the development and normal function of the immune system.8 In addition, microorganisms are involved in the production of neurotransmitters, such as serotonin, vitamin K and vitamin B complex. However, microbiota dysbiosis (a reduction of microbiota diversity, an increase of disease-promoting bacteria, and a decrease of beneficial bacteria) has been associated with different medical conditions.
How has the dysbiosis of gut microbiota been implicated in disease onset and progression?
Dysbiosis of the gut microbiota has been implicated in several serious medical conditions affecting not only the intestine but also other organs and organ systems. Gut microbiota differences have been observed in lean versus obese individuals, as well as people affected by diabetes mellitus versus people not affected by this condition, indicating a role of the gut microbiota in metabolic disorders. Moreover, it is believed that the gut microbiota is involved in immune-related conditions. Presumably, this may occur through the interactions of gut microbiota with the immune system in genetically predisposed individuals and under specific environmental factors.9 Notably, the gut microbiota may also interact with certain drugs and may thus influence their therapeutic effects.
How do the gut and brain interact with each other?
There is an interesting link between symptoms affecting the digestive and central nervous system. For example, an increased rate of depression and anxiety has repeatedly been observed in patients affected by irritable bowel syndrome or ulcerative colitis, which are two serious medical conditions affecting the intestine.10 Moreover, the chances of severe depression are fivefold higher and the chances of severe anxiety fourfold higher in individuals presenting with gastrointestinal symptoms in primary care settings.11 These data speak strongly for the existence of functional interactions between the gastrointestinal and central nervous system.
How can the gut microbiota affect the function of the central nervous system?
The gut microbiota may generate signals that modulate the function of brain cells and affect brain development and function. Researchers have identified molecules that participate in the communication between the gut microbiota and the brain. This includes neurotransmitters, hormones, short-chain fatty acids, and modulators of the immune system. Moreover, the vagus nerve provides a neural connection between the gut and the central nervous system. Furthermore, the immune system plays an important role in the effect of the gut microbiota on the central nervous system through regulation of the function of peripheral and central nervous system-innate immune cells.12
Association of the gut microbiota composition with disorders affecting the central nervous system
Dysbiosis of the gut microbiota has been investigated in association with many different conditions affecting the central nervous system including mental/behavioral; neurodegenerative (characterized by the death of nervous cells or loss of their structure and function) and autoimmune disorders (conditions, in which the immune system of an individual recognizes the body’s own tissues as foreign and attacks them). Thus, an association of the gut microbiota composition with the mental disorders major depressive disorder and schizophrenia, as well as with the neurodevelopmental condition autism spectrum disorder has been observed. Moreover, the composition of gut microbiota has been associated with neurodegenerative conditions including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. Dysbiosis of the gut microbiota has also been observed in patients with multiple sclerosis, an autoimmune disorder affecting the central nervous system. Even though associations between the composition of gut microbiota and disorders of the central nervous system have repeatedly been reported, it is still actively investigated whether dysbiosis of the gut microbiota may have a causative effect on the central nervous system condition, or simply represent a correlation.
Can the gut microbiota be implicated in depression?
Mood disorders are of special interest due to their high prevalence and important public health role. Human moods have been defined as the disposition for a particular way of emotional responses that may be long-lasting, and that a person may not even be aware of consciously.14 The most prevalent mood disorder is depression, which affects approximately 322 million people worldwide and is one of the most important reasons for disability (a condition limiting a person’s potential to perform certain activities and/or to interact with the world around them). People affected by depression feel sad and lose interest in activities, other symptoms (indicators) include problems with sleep (sleeping too little or too much),loss of appetite (having too strong or weak appetite), loss of energy (tiredness), feelings of guilt or worthlessness, impaired concentration, and/or suicidal thoughts. There is a specific threshold regarding the number, intensity, and duration of these symptoms that needs to be fulfilled to allow the clinical diagnosis of major depressive disorder.
The potential implication of gut microbiota in depression has been investigated in different settings. A large cohort study including a discovery dataset of 1,054 samples and validation in independent datasets, found that the abundance of specific gut microorganisms (Coprococcus and Dialister) was consistently decreased among patients with depression. Moreover, the gut microbiota was affected by antidepressant treatment.15 In the same study, the gut microorganisms Coprococcus and Faecalibacterium were also positively associated with certain aspects of quality of life, an important measure used by researchers to assess a person’s happiness and satisfaction level.15 In fact, in one of the datasets, Bacteroides enterotype 2 was associated with higher depression prevalence and lower quality of life.15 Another investigation found differences in the relative abundance of different gut microorganisms between persons affected by depression and healthy individuals. These differences included both overexpression and decrease of certain microorganisms, with increased relative abundance of Actinobacteria and decreased relative abundance of Bacteroidetes, in patients with depression.16
Can the microbiota of pregnant women affect the psychological well-being of their children?
A recent study also addressed the question of whether the fecal microbiota of pregnant women can affect the behavior of their children. Lower diversity of the maternal fecal microbiota during pregnancy was associated with more internalizing problems in children at 2 years of age.17 Internalizing problems indicates symptoms may be related to depression or anxiety. Interestingly, there were indications that a healthy prenatal diet is associated with less internalizing problems in the children through increasing the fecal microbiota diversity of pregnant women. 17
How can the gut microbiota affect human health?
Gut microbiota is characterized by its diversity and important role in a number of biological processes in the human organism including digestion, metabolism, and immune function. However, dysbiosis of the gut microbiota has also been implicated in many medical conditions including metabolic and immunological disorders and conditions affecting the central nervous system. Even though correlations between the composition of the gut microbiota and conditions of the central nervous system have repeatedly been observed, there is still a need to clarify whether gut microbiota dysbiosis may play a causative role in these conditions, and whether there is a potential for its therapeutic modulation.
Literature sources:
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- https://hmpdacc.org/hmp/
- Younge, N., McCann, J.R., Ballard, J., Plunkett, C., Akhtar, S., Araújo-Pérez, F., Murtha, A., Brandon, D., & Seed, P.C. (2019). Fetal exposure to the maternal microbiota in humans and mice. JCI Insight,4(19): e127806. DOI: 10.1172/jci.insight.127806
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- Goodrich, J.K., Waters, J.L., Poole, A.C., Sutter, J.L., Koren, O., Blekhman, R., Beaumont, M., Van Treuren, W., Knight, R., Bell, J.T., Spector, T.D., Clark, A.G., & Ley, R.E. (2014). Human genetics shape the gut microbiome. Cell,159(4): 789–799. doi: 10.1016/j.cell.2014.09.053.
- Leeming, E.R., Johnson, A.J., Spector, T.D., & Le Roy, C.I. (2019). Effect of Diet on the Gut Microbiota: Rethinking Intervention Duration. Nutrients,11(12): 2862. doi: 10.3390/nu11122862.
- Vich Vila, A., Collij, V., Sanna, S., Sinha, T., Imhann, F., Bourgonje, A. R., Mujagic, Z., Jonkers, D., Masclee, A., Fu, J., Kurilshikov, A., Wijmenga, C., Zhernakova, A., & Weersma, R. K. (2020). Impact of commonly used drugs on the composition and metabolic function of the gut microbiota. Nature Communications,11(1):362. https://doi.org/10.1038/s41467-019-14177-z
- Belkaid, Y., & Hand, T.W. (2014). Role of the microbiota in immunity and inflammation. Cell,157(1): 121–141. doi: 10.1016/j.cell.2014.03.011.
- Zheng, D., Liwinski, T. & Elinav, E. (2020). Interaction between microbiota and immunity in health and disease. Cell Research,30: 492–506. https://doi.org/10.1038/s41422-020-0332-7.
- Shah, E., Rezaie, A., Riddle, M., & Pimentel, M. (2014). Psychological disorders in gastrointestinal disease: epiphenomenon, cause or consequence? Annals of Gastroenterology,27(3): 224–230.
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- Fung, T.C. (2020). The microbiota-immune axis as a central mediator of gut-brain communication. Neurobiology of Disease,136: 104714. doi: 10.1016/j.nbd.2019.104714.
- Parodi, B., & Kerlero de Rosbo, N. (2021). The Gut-Brain Axis in Multiple Sclerosis. Is Its Dysfunction a Pathological Trigger or a Consequence of the Disease? Frontiers in Immunology,12: 718220. https://doi.org/10.3389/fimmu.2021.718220
- https://dictionary.apa.org/mood
- Valles-Colomer, M., Falony, G., Darzi, Y., Tigchelaar, E.F., Wang, J., Tito, R.Y., Schiweck, C., Kurilshikov, A., Joossens, M., Wijmenga, C., Claes, S., Van Oudenhove, L., Zhernakova, A., Vieira-Silva, S., & Raes, J. (2019). The neuroactive potential of the human gut microbiota in quality of life and depression. Nature Microbiology,4(4): 623–632. doi: 10.1038/s41564-018-0337-x.
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