Gut Microbiome: The mirror of our health

Written by Dimitra Kousi, Junior Biostatistician, CLEO.

What is the microbiome?

Trillions of microorganisms colonize our gastrointestinal tract, skin, genito-urinary system etc., together forming the ‘human microbiome’. Most of these microorganisms are bacteria, but the microbiome also includes fungi, protozoa and viruses. Some of these microorganisms have a beneficial effect on our health, others have been associated with harmful functions while others remain neutral. 

Recent studies on the human microbiome showed that 56% of the total cell count in our body are not human cells, but bacterial, weighing nearly 0,2 kg (almost as much as a zucchini!) (1). The microbiome is unique for each and every one of us and, in a way, constitutes our identity (2). The vast majority of the human microbial communities inhabit the gastrointestinal tract, and this is the reason why the gut microbiome (GM) has attracted the most attention.

How can we study the gut microbiome?

Rapid advancements in the fields of metagenomics and bioinformatics in the last few decades have shed light on the world of the GM (3). Following the collection of a fecal sample from a person, the genetic material of microorganisms can be isolated. Gene sequencing techniques like 16S rRNA and Shotgun Metagenomic Sequencing are the most common methods used to analyze the genetic material of the sample and describe the GM’s composition, as well as its interactions with the host. It is worth mentioning that Next Generation Sequencing technologies have significantly contributed to the improvement of the efficiency of the aforementioned techniques while also reducing their cost. Together with the advent of Proteomics (4) and Metabolomics (5) that study the protein activity and metabolic processes in our body, respectively, we can get closer to “unlocking” the GM mystery.

What is the role of the gut microbiome in improving our health?

A healthy GM is generally considered to be one with high levels of diversity and which preserves a stable and balanced composition (6, 7). Maintaining a healthy GM has been shown to play an important role in:

  • Regulating our metabolism, by contributing to the fermentation of non-digestible food components and harvesting of nutrients
  • Synthesizing important vitamins, amino acids, as well as metabolic by-products (e.g., butyric acid, propionic acid) that support the functions of the large-intestine
  • Boosting our immune system
  • Fighting off infections caused by pathogens
  • Modulating brain function

Which factors influence the gut microbiome?

Some of the factors that can affect the gut microbiome of a human host are (8, 9):

  • Environment
  • Dietary habits
  • Lifestyle (exercise, smoking, anxiety, etc.)
  • Drug and antibiotic use
  • Childbirth delivery method (natural vaginal delivery, cesarean section)
  • Diseases – Chronic conditions
  • Hormonal changes
  • Aging

How does our gut microbiome change over the years?
From the moment of birth and up until the ages of 3 to 5, the GM changes drastically and it is mainly affected by factors such as environment, diet and antibiotic use (10). Following these crucial first years, the GM acquires an adult-like form that remains relatively stable in later years (11). After the age of 65, the GM’s diversity decreases, while disease-associated microorganisms become more prevalent (12, 13).

Gut microbiome and disease

The disruption of the GM’s balance, also known as ‘dysbiosis’, has been associated with numerous diseases and conditions (14, 15). However, the exact mechanisms of this relationship have not been completely elucidated and remain to be further investigated. Examples of diseases that appear to be linked to ‘dysbiosis’ are:

  • Inflammatory bowel disease
  • Obesity
  • Cardiovascular disease
  • Diabetes
  • Autoimmune diseases, such as psoriasis, autism, etc
  • Depression
  • Neurological disorders, such as Parkinson’s disease, Alzheimer’s disease, etc.
  • Cancer
  • Allergies

What can we do?

Even though we cannot choose our birth delivery method or freeze time, so that we never get old, there are several GM-altering factors that we can control to some extent. Balanced diet, regular exercise, proper use of antibiotics, stress relieving techniques, are a few examples of what we can do to preserve a healthy GM.

With regards to diet, the use of prebiotics and probiotics has been proven to play a significant role in attaining metabolic homeostasis and strengthening the immune system.

Prebiotics, which are undigested carbohydrates that end up in the lowest part of the gastrointestinal tract, are “food” for the beneficial bacteria of the GM, therefore promoting their growth (16). The best-known sources of prebiotics are fruits and vegetables, but there are also prebiotic supplements.

On the other hand, probiotics are precisely those beneficial microorganisms of the GM (17). We can strengthen their presence by consuming certain foods, such as yogurt, peas, sauerkraut, etc., or through food supplements. Regulated intake of these microorganisms may contribute to the maintenance or restoration of the GM’s balance.

Innovative Microbiome-Based Therapies

  • Fecal Microbiota Transplantation (FMT) from healthy donors to people who have been infected by Clostridium difficile is a novel therapeutic method that has been proven to be remarkably efficient (18). There is hope that stool transplant will turn out to be equally successful in treating conditions, such as obesity, several gastrointestinal disorders, etc.
  • Psychobiotics, probiotics that convey mental health benefits to the host (19, 20), could emerge as a promising alternative to the existing psychotropic medications aiming to fight depression, anxiety and behavioural disorders. Many questions that concern the gut-brain connection and the underlying mechanisms of their communication remain currently unanswered. However, what we can say with certainty is that once we manage to lift that veil, the field of Psychiatry will be irrevocably changed.

 

Read more about CLEO's relevant research programme examining the microbiome in the "Blue Microbiome study", here

 

References

  1. Sender, R., Fuchs, S. & Milo, R. Revised Estimates for the Number of Human and Bacteria Cells in the Body. PLoS Biol 14, e1002533 (2016).
  2. Gilbert, J. A. et al. Current understanding of the human microbiome. Nat Med 24, 392–400 (2018).
  3. Bharti, R. & Grimm, D. G. Current challenges and best-practice protocols for microbiome analysis. Briefings in Bioinformatics 22, 178–193 (2021).
  4. Aslam, B., Basit, M., Nisar, M. A., Khurshid, M. & Rasool, M. H. Proteomics: Technologies and Their Applications. J Chromatogr Sci 55, 182–196 (2017).
  5. Belizário, J. E. & Faintuch, J. Microbiome and Gut Dysbiosis. in Metabolic Interaction in Infection (eds. Silvestre, R. & Torrado, E.) vol. 109 459–476 (Springer International Publishing, 2018).
  6. Rinninella, E. et al. What is the Healthy Gut Microbiota Composition? A Changing Ecosystem across Age, Environment, Diet, and Diseases. Microorganisms 7, 14 (2019).
  7. Valdes, A. M., Walter, J., Segal, E. & Spector, T. D. Role of the gut microbiota in nutrition and health. BMJ k2179 (2018) doi:10.1136/bmj.k2179.
  8. Hasan, N. & Yang, H. Factors affecting the composition of the gut microbiota, and its modulation. PeerJ 7, e7502 (2019).
  9. Candela, M. et al. Dynamic efficiency of the human intestinal microbiota. Critical Reviews in Microbiology 41, 165–171 (2015).
  10. Rodríguez, J. M. et al. The composition of the gut microbiota throughout life, with an emphasis on early life. Microbial Ecology in Health & Disease 26, (2015).
  11. Vemuri, R. et al. Gut Microbial Changes, Interactions, and Their Implications on Human Lifecycle: An Ageing Perspective. BioMed Research International 2018, 1–13 (2018).
  12. Salazar, N., Valdés-Varela, L., González, S., Gueimonde, M. & de los Reyes-Gavilán, C. G. Nutrition and the gut microbiome in the elderly. Gut Microbes 8, 82–97 (2017).
  13. Ragonnaud, E. & Biragyn, A. Gut microbiota as the key controllers of “healthy” aging of elderly people. Immun Ageing 18, 2 (2021).
  14. Durack, J. & Lynch, S. V. The gut microbiome: Relationships with disease and opportunities for therapy. Journal of Experimental Medicine 216, 20–40 (2019).
  15. Wang, B., Yao, M., Lv, L., Ling, Z. & Li, L. The Human Microbiota in Health and Disease. Engineering 3, 71–82 (2017).
  16. Wang, S. et al. Rational use of prebiotics for gut microbiota alterations: Specific bacterial phylotypes and related mechanisms. Journal of Functional Foods 66, 103838 (2020).
  17. Kim, S.-K. et al. Role of Probiotics in Human Gut Microbiome-Associated Diseases. Journal of Microbiology and Biotechnology 29, 1335–1340 (2019).
  18. Gupta, S., Allen-Vercoe, E. & Petrof, E. O. Fecal microbiota transplantation: in perspective. Therap Adv Gastroenterol 9, 229–239 (2016).
  19. Del Toro-Barbosa, M., Hurtado-Romero, A., Garcia-Amezquita, L. E. & García-Cayuela, T. Psychobiotics: Mechanisms of Action, Evaluation Methods and Effectiveness in Applications with Food Products. Nutrients 12, 3896 (2020).
  20. Sarkar, A. et al. Psychobiotics and the Manipulation of Bacteria–Gut–Brain Signals. Trends in Neurosciences 39, 763–781 (2016).

 

 

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Center for Clinical Epidemiology and Outcomes Research (CLEO) was founded thanks to a grant from the Stavros Niarchos Foundation, which from 2011 until today continues to support its operation as a major donor.

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