Diversity or function: what defines a healthy microbiota
Within us lies a complex microbial community, the gut microbiome, which greatly impacts our health. It's a site of essential metabolic processes influenced by diet, age and environment. The focus isn’t solely on the variety of microbes, but the essential functions they perform together. Since a healthy state is a dynamic balance between us and these microbes, what defines a healthy microbiome?
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We find ourselves in an era of unprecedented exploration into the microscopic world within us, the gut microbiome. A recent, meticulous scientific review 1 has shed light on this complex ecosystem, revealing both the marvels and the mysteries of our internal microbial communities.
This paper challenges the simplistic view of "dysbiosis", highlighting that this term, often used to describe an imbalanced gut, lacks the precision needed for proper understanding.
It poses also a fundamental question: what truly constitutes a ‘healthy’ microbiome?
What defines a healthy microbiome?
Defining a "healthy" gut microbiome is complex, moving beyond simple absence of disease.
It involves assessing gut structure, function, and microbial composition. While a high diversity of microbial species was once thought to be the primary marker of a healthy gut, it's now understood that (sidenote: Functional Diversity This describes the range of metabolic activities performed by the gut microbiota. It is a more important indicator of gut health than simple taxonomic diversity because different microbial compositions can perform similar metabolic functions. Assessing functional diversity can provide a more accurate prediction of physiological states than compositional diversity alone. ) , the range of metabolic activities the microbiome performs, is more important. This means different microbial compositions can perform similar metabolic functions.
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(sidenote: Strain Specificity This highlights that different strains within the same bacterial species can have vastly different effects on the host. For example, some E. coli strains are pathogenic, while others, like E. coli Nissle 1917, are beneficial. Understanding strain-specific effects is essential for developing targeted therapies and for interpreting research on the gut microbiome. ) is also vital: Different strains within the same species can have vastly different effects. For example, some E. coli strains are pathogenic, while others, like E. coli Nissle 1917, are beneficial.
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Metabolites like (sidenote: Short chain fatty acids (SCFA) Short chain fatty acids (SCFA) are a source of energy (fuel) for an individual’s cells. They interact with the immune system and are involved in communication between the intestine and the brain. Silva YP, Bernardi A, Frozza RL. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front Endocrinol (Lausanne). 2020;11:25. ) , bile acids (BAs), and tryptophan metabolites are key indicators of a functional microbiome. SCFAs, such as butyrate, are essential for colonocyte energy and immune modulation.
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BAs, produced in the liver and modified by gut bacteria, are crucial for fat digestion, signaling and antimicrobial action.
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Other indicators include gas production (hydrogen, methane, hydrogen sulfide), gut pH, and inflammatory markers (calprotectin, lactoferrin).
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Finally, (sidenote: Resilience This refers to the ability of the gut microbiota to maintain a stable composition over time and resist disturbances such as antibiotics or dietary changes. A resilient microbiota can recover quickly from disruptions, reducing the risk of long-term health issues. ) , or the ability of the gut microbiota to resist disturbances, is a crucial marker of a healthy gut.
The mucus layer is also a key component of a healthy gut.
This layer, primarily composed of water, electrolytes, lipids, and mucins, acts as a physical barrier, preventing bacteria from directly contacting the intestinal epithelial cells.
A healthy gut is characterized by an adequate mucus thickness that is not easily penetrable by bacteria. The turnover of the (sidenote: Mucus Layer This is a complex, dynamic barrier lining the gut, primarily composed of water, electrolytes, lipids, and mucins. It physically separates bacteria from the intestinal epithelium, preventing direct contact and maintaining gut barrier integrity. The thickness and turnover of the mucus layer are crucial for a healthy gut. ) which involves synthesis, secretion, and degradation, is a finely tuned process crucial for maintaining proper barrier function.
Factors like prebiotics, such as fructo-oligosaccharides (FOS) and 2′-fucosyllactose (2′FL), can influence mucus production, composition and degradation, enhancing gut barrier integrity and contributing to protection against metabolic disorders.
Disruption of the mucus layer, as seen with some food emulsifiers, can lead to increased intestinal permeability and inflammation.
90-95% Mucus primarily consists of various components, including 90-95% water, electrolytes, lipids (1-2%), proteins and others substances. ¹
45% Approximately 45% of bacterial species are similar between two individuals, their microbiota share 82% common metabolic pathways. ¹
The gut-liver axis: a two-way street
The gut and liver interact closely via the bidirectional gut-liver axis. The liver, as a primary site for detoxification and metabolic regulation, processes and neutralises a variety of environmental toxins, drugs, and metabolic byproducts that are derived from the gut.
The liver produces BAs which are essential for fat digestion and also influence the gut microbiome composition and function. Gut bacteria further metabolise primary BAs into secondary BAs, which have different functions, and some are even associated with longevity.
While the liver is exposed to gut-derived bacterial antigens, it typically does not produce pro-inflammatory cytokines. However, healthy livers produce anti-inflammatory molecules such as IL-1 receptor antagonist (IL-1Ra) to dampen inflammation, as well as specific immunosuppressive macrophages, which are dependent on gut microbiota, to control excessive inflammation.
Factors shaping the microbial ecosystem
The gut microbiome is dynamic, influenced by age, delivery mode at birth, diet and lifestyle.
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Age and delivery mode at birth are critical. Vaginally born infants tend to have a more diverse and balanced gut microbiota, as do breastfed infants, who have a greater presence of beneficial bacteria such as Bifidobacterium spp.
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Diet is paramount. Dietary fibres, prebiotics, polyphenols, and human milk oligosaccharides (HMOs) promote beneficial microbes. In contrast, saturated fats, artificial sweeteners, and emulsifiers can disrupt microbial balance and impair gut barrier function.
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Common emulsifiers, like carboxymethylcellulose (CMC) and polysorbate 80 (P80), disrupt the gut's protective mucus layer, leading to increased gut permeability and inflammation.
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Bioactive lipids also have a crucial, bidirectional role. The host's lipids influence the gut microbiota, and gut microbes produce lipids (e.g., SCFAs, secondary BAs, and other signaling molecules) that impact immune regulation and metabolic health.
A healthy gut microbiome: more than just bacteria
The challenges in defining a universally accepted 'healthy' gut microbiome become increasingly clear. The immense individual variability of the gut microbiome, influenced by genetics, diet, environment, and lifestyle, as well as its dynamic nature, complicates the establishment of universal standards.
The interplay of the gut microbiota, the immune system, and metabolic processes presents a multifaceted challenge. Longitudinal studies are essential to fully understand the dynamic changes within the gut microbiome and their long-term health impacts. This complex area of research calls for a multidisciplinary approach, integrating microbiology, genomics, bioinformatics, clinical research, and personalised medicine.
