The gut microbiome has traditionally been studied for its role in digestion. However, growing scientific evidence suggests that the trillions of microorganisms living in our intestines have a much wider influence on human health.
Researchers have identified connections between the gut microbiome and several organ systems, including the brain, eyes and skin. These relationships involve interactions with the immune system, the production of biologically active compounds and the regulation of inflammation throughout the body. Research into the gut-brain axis1, for example, has revealed how intestinal microorganisms communicate with the nervous system through several biological pathways.
One area attracting particular attention is the role of microbial metabolites, such as short-chain fatty acids2. Produced when certain gut bacteria break down dietary fibre, these compounds help regulate immune responses and maintain the intestinal barrier. Their effects may also extend to organs far beyond the digestive tract.
As research continues, understanding these connections could change how we approach nutrition and the development of targeted formulations for different health conditions.
How does the gut microbiome influence the rest of the body?
The gut microbiome influences health beyond the digestive system through its interactions with the immune system, the compounds it produces and its role in maintaining the intestinal barrier.
An important part of this relationship involves the gut's ability to regulate what enters the bloodstream. The intestinal barrier allows nutrients to pass through while helping prevent harmful substances from entering circulation. Gut bacteria contribute to this protective function, partly through the production of short-chain fatty acids such as butyrate.
The relationship between the gut microbiome and the immune system3 is particularly significant. A substantial proportion of the body's immune cells are associated with the gastrointestinal tract, where they interact with microorganisms and respond to signals produced during microbial metabolism.
Changes in the composition or activity of gut microorganisms can affect these interactions. Scientists use the term dysbiosis to describe disruptions in the microbial community, which have been associated with altered immune responses and inflammation in several health conditions.
These mechanisms help explain why researchers are examining the gut microbiome in relation to organs that, at first glance, appear to have little connection with digestion.
What is the gut-brain axis?
The gut-brain axis is the communication network connecting the digestive system and the brain. It allows signals to travel in both directions, helping explain why changes in gut microbial activity may influence aspects of neurological function and mental health.
One of the main communication routes is the vagus nerve, which carries information between the gut and the brain. Gut microorganisms can also influence this relationship through immune signalling and the production of metabolites that interact with the nervous system.
Research into the microbiota-gut-brain axis1 has examined how these processes may affect stress responses, mood and cognitive function. Particular attention has been given to microbial involvement in the metabolism of tryptophan, an amino acid used by the body to produce serotonin. However, the relationship is complex. Although studies have identified associations between gut microbiome composition and mental health, researchers are still determining which changes have a direct influence on brain function.
Understanding these connections could help scientists identify how nutrition and microbial activity contribute to the biological processes involved in maintaining neurological health.
What is the gut-eye axis?
The gut-eye axis describes the relationship between the gut microbiome and eye health, particularly the role of microbial activity in regulating inflammation and immune responses that may affect the ocular surface.
Although the gut and eyes perform very different functions, they are connected through the body's immune system. Research suggests that changes in gut microbiome composition may influence inflammatory processes associated with ocular health conditions, including dry eye.
A particular area of interest is the production of short-chain fatty acids, especially butyrate. These compounds help maintain the intestinal barrier and regulate immune activity, potentially influencing inflammatory responses beyond the digestive tract.
A review of research into the gut-eye axis4 published in BMC Ophthalmology examined the relationship between intestinal microorganisms and dry eye. The authors discussed evidence linking changes in gut microbiome composition with ocular surface inflammation, while also highlighting the need for further research into the underlying mechanisms.
These findings have prompted greater interest in whether nutritional approaches targeting specific microbial functions could contribute to eye health. A pilot study conducted by Enbiosis evaluating a gut microbiome-targeted formulation reported a 67% improvement in objective tear production, with gains continuing to develop during an eight-week follow-up period after the intervention ended, suggesting that microbial pathways may play a meaningful role in supporting ocular surface health.
What is the gut-skin axis?
The gut-skin axis refers to the relationship between the gut microbiome and skin health, with growing research suggesting that intestinal microorganisms may influence the immune and inflammatory processes involved in maintaining healthy skin.
One possible explanation lies in the way the gut microbiome interacts with the immune system. Microbial metabolites, including short-chain fatty acids, help regulate immune activity and may influence inflammatory responses in tissues beyond the digestive tract.
Researchers have identified associations between gut microbiome composition and inflammatory skin conditions5, including eczema and psoriasis. Some studies have reported differences in microbial diversity and the abundance of particular bacterial groups, although findings vary between populations and health conditions.
The intestinal barrier may also play a role. Changes in its function can affect how microbial products interact with the immune system, potentially contributing to inflammatory activity elsewhere in the body. However, the precise mechanisms connecting these processes to skin health remain under investigation.
While the evidence points towards a relationship between intestinal microbial activity and skin inflammation, further human research is needed to determine whether targeted changes to the gut microbiome can produce consistent improvements in skin health.
How does the gut microbiome affect metabolic health?
The gut microbiome plays a role in metabolic health by influencing how the body processes nutrients, regulates blood glucose and responds to insulin.
One area of particular interest is the relationship between microbial metabolites and glucose regulation. Short-chain fatty acids produced during the fermentation of dietary fibre can interact with receptors involved in appetite regulation and the release of hormones that influence blood glucose levels.
Research has also identified differences in gut microbiome composition among people with type 2 diabetes6, suggesting a possible relationship between microbial activity and metabolic function.
However, diet, genetics and other lifestyle factors can influence both gut microbiome composition and metabolic health. A 12-week pilot study conducted by Enbiosis evaluating a gut microbiome-targeted nutritional formulation reported reductions in fasting blood glucose and HbA1c levels across the majority of participants, suggesting that microbial pathways may represent a meaningful target for metabolic nutrition.
What is the gut-hormone axis?
The gut-hormone axis describes the relationship between the gut microbiome and the body's hormonal systems. Research suggests that intestinal microorganisms may influence hormone metabolism and signalling7, with potential implications for reproductive and metabolic health.
One area of interest is the relationship between gut microbial activity and sex hormones, including testosterone and oestrogen. Studies have identified associations between gut microbiome composition and circulating sex hormone levels⁷˒⁹, while research into oestrogen metabolism suggests that intestinal microorganisms may influence how these hormones are processed and recirculated in the body⁹ . These interactions highlight the potential role of the gut microbiome in maintaining hormonal balance.
The gut microbiome also interacts with hormones involved in appetite and blood glucose regulation. Short-chain fatty acids produced by intestinal bacteria can activate receptors associated with the release of metabolic hormones, including glucagon-like peptide-1 (GLP-1)¹⁰ . This hormone helps regulate insulin secretion, appetite and blood glucose levels, providing another example of how microbial activity may influence processes beyond the digestive system.
Research into these relationships is helping scientists understand how microbial metabolism and hormonal signalling interact. As evidence develops, identifying the pathways involved could support more targeted nutritional approaches to reproductive and metabolic health.
What does this mean for the future of nutrition?
The connections between the gut microbiome and the brain, eyes, skin, metabolism and hormonal systems reveal how microbial activity may influence health throughout the body. Although each relationship involves different biological pathways, they share common mechanisms, including immune signalling, microbial metabolites and the regulation of inflammation.
Understanding these connections is creating new possibilities for more targeted nutritional approaches. ENBIOSIS is exploring this through the world’s first Digital Twin & AI Powered Nutraceutical Formulation Engine, which models gut microbial metabolism to develop condition-specific formulations using food-grade ingredients.
ENBIOSIS has developed a portfolio of condition-specific formulations across these areas, including en-TEAR for ocular surface health, en-CLEAR for skin health, en-JOY&FIT for metabolic health and en-MASCULINE for hormonal balance. Each formulation is developed through the same engine, and clinical investigations are ongoing across these areas. These formulations are available to nutrition and health companies through a licensing model, enabling partners to bring microbiome-targeted products to market under their own brand.
References
- Shekarabi A, Qureishy I, Puglisi CH, Dalseth M, Vuong HE. (2024). Host-microbe interactions: communication in the microbiota-gut-brain axis. Current Opinion in Microbiology, 80, 102494. https://pubmed.ncbi.nlm.nih.gov/38824840/
- Mann ER, Lam YK, Uhlig HH. (2024). Short-chain fatty acids: linking diet, the microbiome and immunity. Nature Reviews Immunology, 24, 577–595. https://pubmed.ncbi.nlm.nih.gov/38565643/
- Wang J, He M, Yang M, Ai X. (2024). Gut microbiota as a key regulator of intestinal mucosal immunity. Life Sciences. https://pubmed.ncbi.nlm.nih.gov/38588949/
- Song J, Dong H, Wang T, et al. (2024). What is the impact of microbiota on dry eye: a literature review of the gut-eye axis. BMC Ophthalmology, 24, 262. https://pubmed.ncbi.nlm.nih.gov/38898418/
- Chen M, Wang R, Wang T. (2024). Gut microbiota and skin pathologies: Mechanism of the gut-skin axis in atopic dermatitis and psoriasis. International Immunopharmacology, 141, 112658. https://pubmed.ncbi.nlm.nih.gov/39137625/
- Mei Z, Wang F, Bhosle A, et al. (2024). Strain-specific gut microbial signatures in type 2 diabetes identified in a cross-cohort analysis of 8,117 metagenomes. Nature Medicine, 30, 2265–2276. https://pubmed.ncbi.nlm.nih.gov/38918632/
- d'Afflitto M, Upadhyaya A, Green A, Peiris M. (2022). Association Between Sex Hormone Levels and Gut Microbiota Composition and Diversity—A Systematic Review. Journal of Clinical Gastroenterology, 56(5), 384–392. https://pubmed.ncbi.nlm.nih.gov/35283442/
- Shin JH, Park YH, Sim M, Kim SA, Joung H, Shin DM. (2019). Serum level of sex steroid hormone is associated with diversity and profiles of human gut microbiome. Research in Microbiology, 170(4–5), 192–201. https://pubmed.ncbi.nlm.nih.gov/30940469/
- Kumari N, Kumari R, Dua A, Singh M, Kumar R, Singh P, et al. (2024). From Gut to Hormones: Unraveling the Role of Gut Microbiota in (Phyto)Estrogen Modulation in Health and Disease. Molecular Nutrition & Food Research, 68(6), e2300688. https://pubmed.ncbi.nlm.nih.gov/38342595/
- Tolhurst G, Heffron H, Lam YS, Parker HE, Habib AM, Diakogiannaki E, et al. (2012). Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes, 61(2), 364–371. https://pubmed.ncbi.nlm.nih.gov/22190648/
