Host-microbiome homeostasis: Unveiling the complex interactions shaping health and disease

The relationship between the human body and its microbial communities is becoming increasingly recognized as essential to our overall health. What we once thought of as a mere collection of bacteria, fungi, and other microorganisms now turns out to play a far more active role in maintaining our health or contributing to disease. This connection, known as host-microbiome homeostasis, refers to the balance between our bodies and the microbes residing within us. When this balance is disrupted, it can lead to conditions such as obesity, asthma, epilepsy, and even heart disease. Recent studies in this field shed light on the nature of this coexistence and pave the way toward therapies that harness the power of the microbiome to treat a variety of health issues.

This special series builds on Acta Physiologica's strong standing in the field^1-3 and comprises studies delving into different aspects of microbiome research. From using engineered bacteria to fight metabolic diseases to exploring the role of diet and early-life microbial exposure in asthma, these studies highlight just how interconnected our health is with the microbes living in and on us.

One of the studies, led by Ciocan and Elinav,⁴ explores the idea of using genetically engineered bacteria to change the gut microbiome in ways that can treat disorders like obesity and diabetes. It is a fascinating step toward developing new treatments that could shift the balance of the microbiome for better health. A further article highlights the gut-lung axis and how early-life microbiota might influence asthma. Early-life exposures to microbes may play a major role in determining whether a child is more likely to develop asthma. Factors like how babies are born, whether they are breastfed, and their early diets all influence the development of their gut microbiome, which in turn affects immune responses. This could mean that by targeting the microbiome early on, there may be new opportunities to prevent asthma before it even begins. Pirr and colleagues explore the neonate respiratory microbiome.⁵ For a long time, we assumed that the respiratory tract was relatively sterile; yet, like the gut, it is home to a variety of microbes. The study reveals how the respiratory microbiome develops in newborns and how factors like delivery method, diet, and early infections can shape the microbial communities in the lungs. Understanding how these microbial communities interact with the immune system could lead to new ways to prevent respiratory diseases in children.

Diet is another area where the microbiome shows its influence, as outlined by Schoeler and his team.⁶ We know that drastic changes in diet can dramatically alter the gut microbiome. This study explores the more subtle effects of typical, everyday dietary variations. By observing how small shifts in diet influence the gut microbiota in both humans and mice, the research suggests that even moderate dietary changes can lead to noticeable changes in microbial composition, potentially offering a more personalized approach to diet-based health interventions.

Moving into the realm of neurology, Diaz-Marugan and colleagues focus on epilepsy.⁷ Some patients with drug-resistant epilepsy struggle to find further treatment options. The microbiome of these patients appears different from that of those whose epilepsy responds to treatment. Interestingly, therapies like the ketogenic diet, which have been used to treat epilepsy, may work by influencing the gut microbiome.

Metformin, a drug commonly used to treat diabetes, has also been shown to have surprising effects beyond blood sugar regulation. Wimmer's study shows that metformin can influence the gut microbiome,⁸ increasing the production of short-chain fatty acids, which have anti-inflammatory effects. These changes were linked to improvements in blood pressure and heart function in rats, even in the absence of diabetes. This finding suggests that metformin could have additional cardiovascular benefits by way of the microbiome, which is an exciting area for further investigation.

The special series illustrates how deeply our health is intertwined with the microbiome and the many ways in which microbial communities can influence everything from metabolism to brain health, and even our immune systems. As we learn more about the microbiome, it becomes clearer that restoring or maintaining a healthy microbial balance could be key to treating a wide range of diseases.^{9, 10} With these findings, the future of medicine may be more about understanding and working with our microbes rather than against them.