What defines a healthy gut microbiome?

Abstract

The understanding that changes in microbiome composition can influence chronic human diseases and the efficiency of therapies has driven efforts to develop microbiota-centred therapies such as first and next generation probiotics, prebiotics and postbiotics, microbiota editing and faecal microbiota transplantation. Central to microbiome research is understanding how disease impacts microbiome composition and vice versa, yet there is a problematic issue with the term 'dysbiosis', which broadly links microbial imbalances to various chronic illnesses without precision or definition. Another significant issue in microbiome discussions is defining 'healthy individuals' to ascertain what characterises a healthy microbiome. This involves questioning who represents the healthiest segment of our population-whether it is those free from illnesses, athletes at peak performance, individuals living healthily through regular exercise and good nutrition or even elderly adults or centenarians who have been tested by time and achieved remarkable healthy longevity.This review advocates for delineating 'what defines a healthy microbiome?' by considering a broader range of factors related to human health and environmental influences on the microbiota. A healthy microbiome is undoubtedly linked to gut health. Nevertheless, it is very difficult to pinpoint a universally accepted definition of 'gut health' due to the complexities of measuring gut functionality besides the microbiota composition. We must take into account individual variabilities, the influence of diet, lifestyle, host and environmental factors. Moreover, the challenge in distinguishing causation from correlation between gut microbiome and overall health is presented.The review also highlights the resource-heavy nature of comprehensive gut health assessments, which hinders their practicality and broad application. Finally, we call for continued research and a nuanced approach to better understand the intricate and evolving concept of gut health, emphasising the need for more precise and inclusive definitions and methodologies in studying the microbiome.

Keywords: barrier function; intestinal microbiology; nutrition.

Figure 1. Spectrum of gut health from diseased to optimal gut functionality. The definition of a healthy gut varies depending on scientific/medical perspective. The narrowest definition focuses pragmatically on the ‘absence of a diagnosed disease or disorder’. A broader definition, the ‘absence of disease or digestive complaints’, acknowledges subclinical issues. The broadest definition, ‘a healthy gut has an ideal gut structure and function, including an optimal microbial composition’, encompasses the gut’s impact on the host. Created with BioRender.com.

Figure 2. Potential markers of a healthy gut microbiota. A healthy gut microbiota is characterised by a diverse and balanced community of microorganisms that perform vital functions for the host. Several key markers have been proposed to assess these, including microbial diversity, composition (abundances, enterotypes, specific species), functionality (metagenomics, enzymatic activities, transcriptomics) and resilience (through long-term monitoring). Production of important metabolites like SCFAs, bile acids and tryptophan derivatives, as well as gases (hydrogen, hydrogen sulfide, methane), are potential indicators. Additionally, gut health indicators such as pH levels and the presence of inflammation markers (like calprotectin, lactoferrin) can be used for assessing overall gut health. SCFAs, short-chain fatty acids. Created with BioRender.com.

Figure 3. The three ‘lines of defence’. Diet and environmental factors influence the microbiome (1), which interacts with the gut barrier (2) to regulate the translocation of luminal components and metabolites. The liver (3) acts as a filter for toxins and metabolites entering through the portal vein. An unhealthy state, associated with alterations in gut microbiota composition, may lead to increased intestinal permeability (‘leaky gut’), allowing pathogens and toxins into the bloodstream. Genetics, age, sex and lifestyle factors modulate these processes. Created with BioRender.com.

Figure 4. Challenges in defining a healthy gut microbiota. In health, the gut microbiota is influenced by bacterial sources, environmental and host factors, creating a complex and dynamic ecosystem with intraindividual and interindividual variability. Alterations in this balance can link microbiota to disease. Key research questions address the diversity, influencing factors, essential functions and the potential for microbiota composition to predict or influence disease development. Created with BioRender.com.