Understanding dysbiosis and resilience in the human gut microbiome: biomarkers, interventions, and challenges

The healthy gut microbiome is important in maintaining health and preventing various chronic and metabolic diseases through interactions with the host via different gut-organ axes, such as the gut-brain, gut-liver, gut-immune, and gut-lung axes. The human gut microbiome is relatively stable, yet can be influenced by numerous factors, such as diet, infections, chronic diseases, and medications which may disrupt its composition and function. Therefore, microbial resilience is suggested as one of the key characteristics of a healthy gut microbiome in humans. However, our understanding of its definition and indicators remains unclear due to insufficient experimental data. Here, we review the impact of key drivers including intrinsic and extrinsic factors such as diet and antibiotics on the human gut microbiome. Additionally, we discuss the concept of a resilient gut microbiome and highlight potential biomarkers including diversity indices and some bacterial taxa as recovery-associated bacteria, resistance genes, antimicrobial peptides, and functional flexibility. These biomarkers can facilitate the identification and prediction of healthy and resilient microbiomes, particularly in precision medicine, through diagnostic tools or machine learning approaches especially after antimicrobial medications that may cause stable dysbiosis. Furthermore, we review current nutrition intervention strategies to maximize microbial resilience, the challenges in investigating microbiome resilience, and future directions in this field of research.