4 Human Health and Disease

Human Health and Disease

The human microbiome plays a vital role in maintaining homeostasis of various organ systems and protecting against infectious agents. It can be subcategorized into local or regional microbiomes throughout the body, such as the gut, oral, skin, lung, and vaginal microbiomes. These manicured microecosystems are highly organized and complex, with each person having their own distinct makeup and distribution of various microorganisms. Though, individual microbiomes are unique, there is still capacity to understand key role players in the community and their potential for adaptation to improve human health in general.

Image showing taxonomy, function, ecology, and dynamics of healthy human microbiomes
Figure 1. Possible definitions of a healthy microbiome: composition, function, dynamics, and ecology. a Early definitions of a “healthy” microbiome generally focused on sets of taxa that might be expected to be found prevalently in healthy people. While purely taxonomic cores of any type have remained elusive, even in relatively narrowly defined populations, each body-site habitat possesses strong phylogenetic enrichments. Typical genera (or families in the gut) in healthy populations at different sites are shown here. b Metagenomic measurements have allowed the functional potential of the microbiome at different sites to be assessed. These studies have yielded more consistently shared functional cores of body-wide and niche-specific pathways that are maintained in health. LPS lipopolysaccharide, PAMP pathogen-associated molecular pattern. c Ecological assembly patterns provide another possible definition of a healthy microbiome, because each host may draw from a “typical” meta-population of potential microbes through a mix of partially stochastic processes. These processes may include the order in which microbes colonize their respective human habitat (affected by geography and early exposures, for example), the prolonged availability of each microbe in the host’s local environment, and host selection. d The healthy microbiome can also be characterized in terms of its dynamics, depicted here in a simplified model as a conceptual energy landscape. The infant microbiome (yellow point) starts out in an unstable state and gradually descends towards one of potentially several healthy adult attractor states. Perturbations (dashed red arrows) can either be resisted (green point) or can move the microbiome out of the healthy state, after which a resilient microbiome will return to a healthy state (not necessarily the original healthy state) or fall into an unhealthy state (red). (Lloyd-Price et al., 2016).

Disruption, or dysbiosis, of the microbiome can cause serious diseases and allow for opportunistic infections to occur. This disturbance can be caused by a variety of factors including changes in diet, exercise, geographical location, age, habits, as well as medical intervention like antimicrobial chemotherapy. This change in microbial composition subsequently leads to the development and exacerbation of a number of diseases impacting essentially every aspect of human physiology including the digestive, respiratory, integumentary, central nervous, and reproductive systems. Alternatively, dysbiosis may be the result of a particular disease, and in other cases disease-dysbiosis may be bidirectional (Silverman et al., 2019). The human microbiome can be influenced by many of the above mentioned factors, but also others like life partners, pet ownership, and occupation, which do not necessarily correlate with or contribute to dysbiosis (Kiecolt-Glaser et al., 2019, Kates et al., 2020).

A major driving feature of many of these elements is the host’s genetics, which can also directly impact their microbiome (Tabrett and Horton, 2020). Part of the gut microbiome and even individual types of bacteria have been shown to be heritable (Kurilshikov et al., 2017), and it is likely that other areas of the human microbiome, like the skin microbiome, could be passed from parent to offspring as well (Si et al., 2015). The host genotype is intimately linked to its microbiome and has been shown to affect dysbiosis-induced diseases such as inflammatory bowel disease and atopic dermatitis (Knights et al., 2013, Dabrowska and Witkiewicz, 2016, Woo and Sibley, 2020). Host genetics and their microbiome can even indirectly affect one’s susceptibility to other diseases. For example, the attractiveness of mosquitos to particular individuals is an heritable trait which is influenced by the many factors, including the skin microbiome; therefore altering the potential of contracting a mosquito-borne pathogen, such as a Plasmodium parasite which causes malaria (Martinez et al., 2020). It seems there is a combination between environmental factors, host genetics, behavior, and others that continually build and adapt the human microbiome, however, is worthy to note that the former may play a larger role in shaping particular microbiomes, such as the gut microbiome (Rothschild et al., 2018).

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References

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