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

Abstract

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.

Keywords: antibiotics; biomarkers; dysbiosis; human gut microbiome; microbiome recovery; perturbation; resilient gut microbiome.

Figure 1

Known factors that impact the composition and function of human gut microbiome. Various intrinsic and extrinsic stressors contribute to short-term, long-term, or permanent alteration of microbial communities. Medications, especially antibiotics, and infections by gastrointestinal pathogens may cause long-term dysbiosis by permanent changes in the relative abundance of major phyla, especially the ratio of Bacillota (Firmicutes) to Bacteroidota and reducing the abundance of beneficial bacteria, especially SCFA bacteria that may influence the function of HGM. Chronic and metabolic diseases may be caused by changes in the gut microbiome or may influencing the gut microbiome composition and function (Created in BioRender. Safarchi, A. (2025) https://BioRender.com).

Figure 2

Response of the human gut microbiome to weak and strong stressors. (A) Temporal changes and recovery of microbiome composition, diversity and function under weak and strong stressors illustrated from a resistant to a resilient or susceptible gut microbiome. The impact of this changes may also vary from small to high changes (vertical axis). Recovery to baseline may take a few days for weak stressors (e.g., short-term travel, short-term dietary changes, etc) to several months for strong ones (horizontal axis), with faster recovery observed in resistant and resilient microbiomes. In susceptible microbiomes or individuals with specific conditions (e.g., genetics, environment and lifestyle, infections, medication, cancers, metabolic disorders), the gut microbiome may not return to baseline, leading to stable dysbiosis or prolonged recovery times. The time and intensity of the response to disturbance factors vary among resistant, resilient, and susceptible gut microbiomes. (B) Four human gut microbiome recovery scenarios following exposure to strong disturbance factors. Microbiome composition and function can fully or partially recover or remain unrecovered, resulting in stable dysbiosis. The abundance of SCFA-producing bacteria and Bacteroides taxa in the baseline microbiome plays a crucial role in the recovery of both the composition and function of the human gut microbiome (Created in BioRender. Safarchi, A. (2025) https://BioRender.com).

Figure 3

Nonspecific and specific biomarkers associated with a resilient gut microbiome. Certain biomarkers, including diversity metrics and a greater abundance of beneficial taxa and antimicrobial compounds, are commonly found in resilient and healthy microbiota. These biomarkers are essential for maintaining gut health, promoting resilience, and facilitating faster recovery. Specific biomarkers highly correlated with resilience include recovery-associated bacterial taxa (e.g., Bacteroides, Alistipes, Parabacteroides, and Akkermansia, etc.) and a higher proportion of beneficial bacteria, such as SCFA-producing and bacteriocin-producing bacteria. Additionally, specific antimicrobial peptides (e.g., REG3G) and bacteriocins (e.g., BSAP-3, Acodocin, pINC8, and PIS) play a crucial role in maintaining microbiome stability and recovery by inhibiting the growth and colonization of opportunistic and pathogenic bacteria. These specific biomarkers are likely to play a significant role in maintaining gut resilience and may serve as indicators of a resilient microbiome (Created in BioRender. Safarchi, A. (2025) https://BioRender.com).