19.2: The Human Microbiome

Learning Objectives

• Describe the goals and major accomplishments of the Human Microbiome Project (HMP) and iHMP
• Explain how microbial communities vary across different body sites
• Analyze how local conditions (e.g., moist, dry, or oily) influence microbiome composition

The Human Microbiome

It was evident that the human microbiome and its involvement in a micro and macro scale needed to be characterized. The Human Microbiome Project (HMP) set out in 2007 with this as one of its primary goals (Turnbaugh et al., 2007). The program also set out with initiatives to develop a set of microbial genome sequences, explain the relationship between disease and microbiome changes and evaluate the data with multi-omics approaches, develop new tools and technology for computational analysis, establish a data analysis and coordinating center and research repositories, as well as address ethical, social, and legal implications of HMP research (Human Microbiome Project). The second phase of the HMP launched in 2014, called the Integrative Human Microbiome Project (iHMP), having the main mission to completely characterize the human microbiota with a key focus on human health and disease using three projects: pregnancy and preterm birth, onset of inflammatory bowel disease (IBD), and onset of type 2 diabetes (NIH Human Microbiome Project, The Integrative HMP (iHMP) Research Network Consortium, 2019). Aside from these, the human microbiome and disruption of the microbiota has been linked to several other important conditions and diseases including multiple sclerosis, diabetes (types 1 and 2), allergies, asthma, autism, and cancer (Backhed et al., 2012, Hsiao et al., 2013, Petersen and Round, 2014, Trompette et al., 2014, Garrett, 2015, Lloyd-Price et al., 2016).

Figure \(\PageIndex{1}\): This diagram shows the microbial composition across different sites on the human body, highlighting variation by location and skin type (oily, moist, or dry). Each site’s pie charts represent the relative abundance of bacteria, fungi, and other microbial kingdoms. Dominant bacterial genera include Propionibacterium, Corynebacterium, and Staphylococcus, while Malassezia is the primary fungal genus. The figure illustrates how microbial communities are shaped by local environmental conditions. "Microbiome Sites" by National Human Genome Research Institute is licensed under CC BY 2.0.

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It makes sense that the human microbiome can have such an impact on human health and behavior if you consider that we are essentially a collection of organisms forming a living entity. In a way, our symbionts may even actually define more of who we are than just our own unique biological makeup. For instance, the ratio of microbial cells associated with a human body could equal, if not exceed (traditional estimates were tenfold), the number of human cells (Sender et al., 2016). Even more interesting is viewing our genetic makeup; the human genome contains about 20,000 genes, but its hologenome contains > 33 million genes brought by its microbiota (Huttenhower et al., 2012, Lloyd-Price et al., 2016, Simon et al., 2019). Furthermore, the composition and rate of change of each person’s microbiota is distinctive from one individual to another since it is influenced by variables like age, lifestyle, diet, antibiotics, occupation, environment, etc. (Gilbert et al., 2018). The genetic wealth and member diversity contributed from the microbiota has roles in adaptation, survival, development, growth, and reproduction of the holobiont and can affect fitness in the short term as well as have long lasting effects concerning the evolution of both partners (Rosenberg, and Zilber-Rosenberg, 2011).

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Co-evolution of the host-microbiota symbiosis can be considered even more unique when viewing the microbial consortium at different locations or organs in the host, as their makeup is governed by and reflects specific physiological processes in those areas. For example, the bacteria found in the human gut microbiota are primarily from the phyla Bacteroides and Firmicutes, whereas Actinobacteria and Proteobacteria command the skin microbiome, though there is some overlap and it is important to note that there are differences depending on exact location (e.g. dry vs. moist areas of the skin) (Grice and Segre, 2011, Jandhyala et al. 2015). Though there are differences between various microbiota within a holobiont, they can still influence each other to some degree. In the case of the gut and skin microbiotas in humans, deemed the ‘gut-skin axis’, there are indications that both the health of the gastrointestinal (GI) tract and skin, as well as their response to stressors, are correlated (Levcovich et al., 2013, O’Neill et al., 2016, Salem et al. 2018). Even more interesting is the effects certain microbiota can have on germ-free organs like the brain. Studies on the ‘gut-brain axis’ show that the microbiota in the GI tract, and in some cases disruption of it, are associated with many mental illnesses and neurodegenerative disorders including depression, anxiety, autism, schizophrenia, Parkinson’s disease, and Alzheimer’s disease (Clapp et al. 2017, Foster et al. 2017, Cryan et al. 2019). A variety of different ‘axes’ which demonstrate interplay between microbiota, organs, and locations have been identified in the human body and much of what is known about their connections is novel and early in its research.

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Key Concepts and Summary

• The Human Microbiome Project (HMP) was launched in 2007 to characterize the human microbiome, explore its connection to health and disease, and develop tools for microbial genomics and data analysis.

• The Integrative Human Microbiome Project (iHMP), launched in 2014, focused on microbiome changes related to pregnancy/preterm birth, inflammatory bowel disease (IBD), and type 2 diabetes.

• Disruptions to the human microbiome have been associated with a wide range of diseases and conditions, including allergies, asthma, cancer, and neurological disorders.

• The microbiome is site-specific, varying by body location (e.g., gut, skin), and is influenced by environmental conditions such as moisture and pH.

• Humans are holobionts - a complex ecosystem of host and microbial cells—where the microbiota contributes the majority of genetic content (the hologenome).

• The microbiome is shaped by lifestyle, diet, age, antibiotic use, and environment, resulting in highly individualized microbial communities.

• Key symbiotic pathways such as the gut-skin axis and gut-brain axis illustrate the deep interconnection between microbiota and host systems, including immune, nervous, and integumentary systems.

Media Attributions

• Video 1 – What is the human microbiome? by The Conversation. Licensed under Creative Commons: By Attribution 3.0 License https://creativecommons.org/licenses/by/3.0/
• Video 2 – Human Science (Part I) – The Gut Brain Axis, Microbiome & the power of Probiotics by Infognostica. Licensed under Creative Commons: By Attribution 3.0 License https://creativecommons.org/licenses/by/3.0/
• Figure 1 – Microbiome Schematic by Berg et al., 2020 adapted by Dylan Parks. Licensed under Creative Commons: By Attribution 4.0 License http://creativecommons.org/licenses/by/4.0/
• Figure 2 – History of Microbiome Research by Berg et al., 2020. Licensed under Creative Commons: By Attribution 4.0 License http://creativecommons.org/licenses/by/4.0/

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