Although gut microbiota profiles differ remarkably between healthy individuals, several features have been suggested to define a “healthy gut microbiome”. First of all, our gut microbiota can be understood, in many cases, to be redundant given that many bacterial species have similar functions. Furthermore, a healthy gut microbiome is temporally stable and resistant to perturbations and, over time, is more similar to itself than to that of another healthy person. Finally, a healthy gut microbiome is resilient, which means that it returns to a healthy state after a perturbation. For example, after antibiotic treatment, our gut microbiota usually recovers to its previous state a few weeks or months later. As such, a plausible definition of microbial health does not comprise a single static state, but rather a dynamic equilibrium. Meanwhile, when a perturbation stimulus becomes chronic and leads to an altered stable gut microbiome that causes harm to the host, this is called dysbiosis.

In the context of the homeostatic capacity of a host, the European Food Safety Authority (EFSA) has defined resilience as “the amount of disturbance that can be absorbed by a system before the system changes or loses is normal function, or the time taken to return to a stable state”. A biological system, including that of humans, enters a transient state when exposed to a disturbance, and resilience may well help with reaching a healthy steady state.

When considering human wellbeing and our gut microbiota as an ecosystem, the concept of resilience enables a person to remain healthy or recover faster when exposed to environmental stressors including xenobiotics, physical and psychological stress and unbalanced diets. Once it is established, at around 2 to 3 years of age, the human gut microbiota finds a relatively stable state. Indeed, it has been reported that while the composition of the microbiome changes drastically over the first years of life, this functional profile in the gut is established early on and the so-called “core” healthy microbiome remains stable thereafter. Regarding community assembly, current research about the health effects of human microbes during early life shifts the focus away from ‘how they got there’ toward ‘who got there in what order’.

Although dietary changes and drug administration can move the gut microbiota to alternate stable states, our microbiota usually reaches a stable state that is similar to yet distinctly different from the basal state. The magnitude of disturbance and the speed and extent of recovery varies across individuals and even within an individual. Defining baseline healthy microbiomes is a current challenge, as is identifying features that reflect deviations therefrom, given the large degree of complexity and variability of the gut microbiome during our lifespan.

The mechanisms that confer resilience to a microbiota’s stable states include species richness, functional response diversity, competition in the densely populated gut environment and specific changes involving a complex relationship with the gut microbiota and its host.

In addition to gut microbiota resilience, the immune system is also involved in maintaining a passive response to food, environmental components and the commensal gut microbiota, which are not threatening under normal conditions. For instance, although inflammation is part of a normal host response to infection, overactive immune responses with chronic inflammation are deleterious and may lead to chronic inflammatory diseases such as rheumatoid arthritis and obesity. Furthermore, the indirect communication between nutrition, gut microbiota and the host immune response highlights the fine-tuned role of gut microbiota in modulating the immune response through diet.

Taking into account these data, it is not surprising that, considering both its composition and functional diversity, the ability of the colonizing gut microbiota to resist or recover fast from perturbations reflects a person’s ability to remain healthy. Thus, resilience arises as an emerging biomarker of health.

In a commentary, Mary Ellen Sanders and colleagues considered the stability of the gut microbiota as a biomarker for homeostasis, stating that improved homeostasis leads to a minimum variation around the mean for a specific measure following an intervention. This, indeed, implies the assumption that a narrow control of the measured parameter—in this case, gut microbiota composition and/or functional diversity—is physiologically advantageous for the host.

Even though we do not currently have a specific biomarker that can be used as a unique outcome in dietary intervention studies, the measurement of gut microbiota composition and/or functional properties, together with other immune, biochemical and metabolic parameters, might help provide a clearer picture of host homeostatic capacity. Thus, a better understanding of the resilience mechanisms of both harmful and beneficial gut microbial communities will enable novel treatment strategies to be designed (for instance, genetic engineering probiotics for improved bacterial resilience and colonization) that will maintain the health of the gut microbial ecosystem and, in turn, its human host.

 

 

References:

Bäckhed F, Fraser CM, Ringel Y, et al. Defining a healthy human gut microbiome: current concepts, future directions, and clinical applications. Cell Host Microbe. 2012; 12(5):611-22. doi: 10.1016/j.chom.2012.10.012.

EFSA Scientific Committee. Guidance on the assessment of the biological relevance of data in scientific assessments. EFSA Journal. 2017; 15(8):4970. doi: 10.2903/j.efsa.2017.4970.

Greenhalgh K, Meyer KM, Aagaard KM, Wilmes P. The human gut microbiome in health: establishment and resilience of microbiota over a lifetime. Environ Microbiol. 2016; 18(7):2103-16. doi: 10.1111/1462-2920.

Lozupone CA, Stombaugh JI, Gordon JI, et al. Diversity, stability and resilience of the human gut microbiota. Nature. 2012; 489(7415):220-30. doi: 10.10138/nature11550.

Sanders ME, Heimbach JT, Pot B, et al. Health claims substantiation for probiotic and prebiotic products. Gut Microbes. 2011; 2(3):127-33. doi: 10.4161/gmic.2.3.16174.

Sprockett D, Fukami T, Relman DA. Role of priority effects in the early-life assembly of the gut microbiota. Nat Rev Gastroenterol Hepatol. 2018; 15(4):197-205. doi: 10.1038/nrgastro.2017.173.

Andreu Prados
Andreu Prados
Andreu Prados holds a Bachelor of Science Degree in Pharmacy & Human Nutrition and Dietetics. Science writer specialised in gut microbiota and probiotics, working also as lecturer and consultant in nutrition and healthcare. Follow Andreu on Twitter @andreuprados