The Gut Microbiota and its Impact on Human Health

By Tanjim Sayeeda

Our bodies are inhabited by trillions of microorganisms ranging from archaea, protozoa, single-celled eukaryotes and viruses (Eloe-Fadrosh & Rasko, 2013). These microscopic organisms, termed microbiota, outnumber human cells 10 to 1 and are extremely rich in their diversity (Sender, Fuchs & Milo, 2016). They form various relationships with their hosts, such as commensal and parasitic, or, as is the case in humans, symbiotic. The human microbiota forms an ecological community within a specific area of the body such as the skin, nose, mouth and gut (Safaa, Hatice Kubra & Hasibe Cingilli, 2020). 

The human gut is colonised by 10¹⁴ microbes and thus is the largest community within the human microbiota (Ursell et al., 2012). These commensal bacteria begin colonisation of the gut as early as birth, and the composition changes and develops throughout growth. The gut microbiota is important for the general health and development of humans as they aid growth, assist the immune system and help with digestion as well as mood regulation. The compositions of the human microbiota depend on various physiochemical factors like pH, host secretions and nutrients. However, external factors such as lifestyle, stress and age can also influence the composition (Zhang et al., 2015). 

The microbiome refers to the genes that microorganisms harbour; many microbiome projects have been launched to help understand the symbiotic roles microorganisms may play within the human body. Interest towards the gut microbiome has increased over recent years due to the rapidly advancing sequencing technology nourishing large scale projects such as the Human Microbiome Project funded by United States National Institutes of Health that aspire to identify and characterise microbial species that make up the human microbiota. One of the projects being focused on is the onset of inflammatory bowel disease (IBD); multi-institutional effort is being made to understand how the gut microbiome develops over time for adults and children affected by IBD. Current research displays that the symbiotic relationship between host and gut microbiota is based on complex metabolic, neuroendocrine and immune interactions mediated by metabolites synthesised by microbes (Kho & Lal, 2018). 

The composition and diversity of the gut microbiota is thought to be linked to multiple health conditions. Gastrointestinal conditions such as IBD, irritable bowel syndrome and other systemic conditions such as obesity, type 2 diabetes and atopy are linked with an imbalance in normal gut microbiota known as dysbiosis. Other diseases that dysbiosis may be responsible for are allergies, diabetes, obesity and cancer. 

A healthy gut would be comprised of mainly strict anaerobes and fewer facultative anaerobes (organisms that have the capability of growing anaerobic conditions too). The microbiota is usually dominated by two bacteria phyla: Bacteroidetes and Firmicutes which are involved in metabolism of undigested food (Bull & Plummer, 2014). Gut bacteria live alongside the host in a commensal manner as they can supply nutrients, synthesise Vitamin K, aid cellulose digestion and promote enteric nerve function as well as angiogenesis; these commensal bacteria in return receive an abundance of nutrients from the host (Zhang et al., 2015).

One problem with research into the microbiome is answering the question of whether an unhealthy gut microbiota (lacking in diversity and composition) is correlative or consequential to disease? Assessing this question is made more difficult due to the confounding factors that are also known to affect the composition of gut microbiota; these include physiological and lifestyle differences between individuals. It is easy to misclassify a correlation between gut microbial composition and a disease if confounding factors such as age and gender are also affecting composition. A solution proposed to tackle this issue was one-to-one matching with individuals  who shared the same age, gender and body mass index before comparison of gut microbiota is proceeded. When seeking differences between an affected individuals and healthy individual, there will be a statistically significant association between the disease and the abundance of certain bacteria in the gut. Contrastingly, when individuals who may or may not have the disease are matched with a confounding factor involved, the associations will not be statically significant. In this case, the diseases are most probably not stemming from the gut microbiota but another underlying issue. An example of this is how alcohol consumption can decrease the diversity of bacteria in the gut microbiota, and thus lead to misleading conclusions about the root of the disease (Anon., 2020). 

Understanding the microbiota and the causal relationship it potentially has with human disease is a key topic of research that could benefit medicine to treat and identify susceptibility to many diseases of today. 

References:

(Nov 4, 2020) Identifying gut microbes that affect human health. Nature (London). Available from: https://search.proquest.com/docview/2457969154 .

Sender, R., Fuchs, S. & Milo, R. (2016) Revised Estimates for the Number of Human and Bacteria Cells in the Body. PLoS Biology. 14 (8), e1002533. Available from: https://search.datacite.org/works/10.1371/journal.pbio.1002533. 

Bull, M. J. & Plummer, N. T. (2014) Part 1: The Human Gut Microbiome in Health and Disease. Integrative Medicine (Encinitas, Calif.). 13 (6), 17-22. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26770121.

Eloe-Fadrosh, E. A. & Rasko, D. A. (2013) The Human Microbiome: From Symbiosis to Pathogenesis. Annual Review of Medicine. 64 (1), 145-163. Available from: http://dx.doi.org/10.1146/annurev-med-010312-133513. Available from: doi: 10.1146/annurev-med-010312-133513.

Kho, Z. Y. & Lal, S. K. (2018) The Human Gut Microbiome – A Potential Controller of Wellness and Disease. Frontiers in Microbiology. 9 1835. Available from: https://search.datacite.org/works/10.3389/fmicb.2018.01835. 

Safaa, A., Hatice Kubra, Y. & Hasibe Cingilli, V. (2020) Interaction of the microbiota with the human body in health and diseases. Bioscience of Microbiota, Food and Health. 39 (2), 23-32. Available from: http://mol.medicalonline.jp/en/journal/download?GoodsID=ef8bomfh/2020/003902/001&name=0023-0032e.

Ursell, L. K., Metcalf, J. L., Parfrey, L. W. & Knight, R. (2012) Defining the human microbiome. Nutrition Reviews. 70 (8), S38-S44. Available from: https://search.datacite.org/works/10.1111/j.1753-4887.2012.00493.x. 

Zhang, Y., Li, S., Gan, R., Zhou, T., Xu, D. & Li, H. (2015a) Impacts of Gut Bacteria on Human Health and Diseases. International Journal of Molecular Sciences. 16 (12), 7493-7519. Available from: https://search.datacite.org/works/10.3390/ijms16047493. 

Zhang, Y., Li, S., Gan, R., Zhou, T., Xu, D. & Li, H. (2015b) Impacts of Gut Bacteria on Human Health and Diseases. International Journal of Molecular Sciences. 16 (12), 7493-7519. Available from: https://search.datacite.org/works/10.3390/ijms16047493.