91桃色

Gut-immune axis; Gastrointestinal inflammation; Intestinal microbiota; Mucosal immunity; Inflammatory bowel disease; Gut barrier dysfunction

Introduction

The gastrointestinal (GI) tract is not only a site of nutrient absorption but also a central hub of immune activity, hosting the largest population of immune cells in the body [1]. This intricate relationship between the gut and the immune system referred to as the gut-immune axis plays a vital role in maintaining intestinal homeostasis and protecting against pathogenic insults. However, when this balance is disrupted, it can trigger a cascade of immune responses that result in chronic inflammation and gastrointestinal pathology [2]. At the heart of the gut-immune axis lies a dynamic interplay between intestinal epithelial cells, mucosal immune components, and the gut microbiota. Under normal conditions, these elements work synergistically to promote immune tolerance, support barrier integrity, and suppress inappropriate inflammatory responses. Yet, alterations in microbial composition (dysbiosis), genetic predispositions, environmental exposures, or infections can lead to aberrant immune activation [3].

This dysregulation is increasingly recognized as a key factor in the pathogenesis of inflammatory bowel diseases (IBD) such as Crohn’s disease and ulcerative colitis, as well as other GI disorders including celiac disease, irritable bowel syndrome (IBS), and colorectal cancer [4]. In these conditions, persistent immune activation leads to tissue damage, compromised barrier function, and further immune dysregulation—a vicious cycle perpetuating disease progression. Understanding the molecular and cellular mechanisms governing the gut-immune axis is crucial for identifying novel diagnostic markers and therapeutic targets. As research continues to uncover the profound influence of the microbiota and immune signaling pathways, the gut-immune axis stands at the forefront of personalized medicine in gastroenterology [5].

Discussion

The gut-immune axis functions as a finely tuned network that integrates signals from the intestinal microbiota, epithelial barrier, and immune system to maintain gastrointestinal (GI) homeostasis [6]. Disruption of this balance often initiates or exacerbates inflammation-mediated pathology, underlying several chronic and acute GI disorders. Central to this discussion is how the interplay between dysbiosis, immune dysregulation, and barrier dysfunction leads to persistent inflammation and tissue injury [7]. One of the key elements influencing the gut-immune axis is the intestinal microbiota. Commensal microbes not only aid in digestion but also modulate the development and activity of both innate and adaptive immune responses. In a healthy state, microbial metabolites like short-chain fatty acids (SCFAs) help reinforce the intestinal barrier and suppress pro-inflammatory cytokine production. However, when dysbiosis occurs often due to antibiotics, diet, or environmental exposures it can promote the expansion of pathogenic species and reduce microbial diversity, triggering inappropriate immune activation [8].

Immune dysregulation plays a critical role in this inflammatory cascade. In diseases like Crohn’s disease and ulcerative colitis, there is often an overproduction of pro-inflammatory cytokines such as TNF-α, IL-6, IL-17, and IFN-γ, along with impaired regulatory T-cell (Treg) function. This skewed immune response not only damages intestinal tissues but also perpetuates inflammation by attracting more immune cells to the site. Emerging evidence suggests that defects in pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs) and NOD-like receptors (NLRs), also contribute to sustained inflammation by failing to discriminate between commensal and pathogenic microbes. Another key player is the intestinal epithelial barrier, which physically separates luminal contents from immune-rich lamina propria. When this barrier is compromised—due to inflammation, epithelial apoptosis, or genetic defects it allows microbial antigens and toxins to translocate into deeper tissues, exacerbating the inflammatory response. This "leaky gut" phenomenon is both a cause and consequence of chronic GI inflammation [9].

Interestingly, the gut-immune axis also exhibits bidirectional communication with other systems, such as the central nervous system (CNS) and liver, highlighting its systemic relevance. For example, alterations in gut immunity and microbiota have been linked to neuroinflammation in disorders like Parkinson’s disease, and to metabolic disturbances in nonalcoholic fatty liver disease (NAFLD). Recent therapeutic strategies have focused on modulating the gut-immune axis through the use of biologics, probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary interventions. Anti-TNF therapies and integrin antagonists have shown success in IBD, while personalized microbiome-based therapies are under active investigation. These approaches underscore the therapeutic potential of restoring immune tolerance and microbial balance within the gut. In sum, the gut-immune axis is a pivotal regulator of GI health and disease. Its complexity stems from the continuous dialogue between immune cells, microbial residents, and the epithelial barrier. Understanding this triad and its role in inflammation not only provides insight into the pathogenesis of GI disorders but also opens avenues for precision-targeted interventions aimed at restoring mucosal homeostasis [10].

Conclusion

The gut-immune axis stands at the core of gastrointestinal health, orchestrating a delicate balance between immune tolerance and defense. When this balance is disrupted through microbial dysbiosis, immune dysfunction, or barrier compromise it paves the way for chronic inflammation and the onset of a wide range of gastrointestinal pathologies. Conditions such as inflammatory bowel disease, celiac disease, and other inflammatory disorders of the gut exemplify the profound impact of an imbalanced gut-immune relationship. Advancements in our understanding of the molecular and cellular mechanisms governing this axis have highlighted the interdependence of the intestinal microbiota, epithelial integrity, and mucosal immune responses. These insights have not only unraveled the complexity of gut-related inflammation but have also driven the development of novel diagnostic and therapeutic approaches aimed at restoring intestinal equilibrium. As we move toward a more personalized and integrative approach in medicine, targeting the gut-immune axis holds significant promise for preventing, diagnosing, and managing inflammation-driven gastrointestinal diseases. Continued research into the interactions within this axis will be essential for developing precise, microbiome-informed strategies that promote long-term intestinal health and systemic well-being.

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