Fig. 6

The conceptual model of homeostatic reprogramming mediated by commensal microbes. a The concept of ‘Homeostatic reprogramming’ is used to describe a phenomenon in which the adaptive genome (commensal microbiota) coordinates with the innate genome (human cell/tissues) to deviate the scope and regulation outcome from the original trajectory including body temperature, uric acid levels, glucose level, blood pressure, etc. The interplay between human life stages - from youth to old age - and microbial development - from increasing to decreasing diversity - overall results in different regulatory forces. b The conceptual model of cell-microbe co-ecology and co-homeostasis. Plasma, tissue fluid and lymphatic fluid form the internal environment of the human body’s cell life. This internal environment is regulated by the neural, immune, and metabolic systems to maintain a dynamic homeostasis of physical and chemical properties such as temperature, pH, and osmotic pressure. The internal factors of cell differentiation, proliferation, ageing, damage, and apoptosis can affect this homeostasis. Human tissues are involved in shaping a physico-chemical and nutritional environment where external microorganisms can colonize, replicate, experience loss and die. On the one hand, human cells, and microorganisms in the digestive tract work together to metabolize nutrients from food. Microbes not only affect nutrient absorption, but also produce metabolites, vitamins, and potential “dark matter”, which can enter the internal environment and affect its homeostasis. The imbalance of the internal environment also leads directly to the disruption of the microenvironment they form. The diversity, relative abundance, and products of beneficial, harmful, and neutral microorganisms (composition) are important indicators for assessing the environmental balance. On the other hand, microorganisms also participate in shaping the microenvironment by providing a barrier to respond to external environmental changes. This overall change regulates the susceptibility of the internal environment to external perturbations, acting another regulatory force for homeostasis