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Breakthrough Study Reveals Surprising Complexity of Neutrophils in IBD Neutrophils, the immune cells long thought to be simple antimicrobial agents, are much more intricate than previously believed, according to a recent review published in 'Nature Reviews Gastroenterology and Hepatology'. The study sheds light on the diverse functions and phenotypes of these cells and their crucial role in inflammatory bowel disease (IBD), specifically Crohn’s disease and ulcerative colitis, as well as their interaction with the gut microbiota. Traditionally seen as defenders against pathogens, the study highlights that neutrophils also contribute to chronic inflammation and tissue damage in IBD. They employ various mechanisms, including reactive oxygen species (ROS), cytotoxic granules, and neutrophil extracellular traps (NETs), which can actually harm the mucosal lining. However, specific subsets of neutrophils can also aid in tissue repair and inflammation resolution, showcasing a dual role. Over 350 IBD susceptibility genes are associated with neutrophil functions, underlining their significance in disease development and their involvement in the complex dynamics between the host and microorganisms

These findings underscore the need for further research to fully grasp neutrophils' roles in IBD and explore potential targeted therapies that can modulate their functions without compromising their essential tasks. The interaction between neutrophils and the gut microbiota is of utmost importance. Neutrophils play a pivotal role in encapsulating commensal microorganisms during inflammation and maintaining the balance of microbial populations in the gut. Their recruitment to the intestinal mucosa is vital for this equilibrium and is guided by chemotaxis receptors and cytokines. However, when neutrophil infiltration becomes chronic, it alters the intestinal environment, promoting the growth of harmful bacteria while releasing antimicrobial peptides that impact the composition of the microbiota. Interestingly, the microbiota itself has a significant impact on neutrophil functions, influencing their development, recruitment, activation, and maturation

This relationship becomes especially pronounced in IBD, where direct interactions between the microbiota and immune cells are more prevalent. Excitingly, preclinical evidence suggests that natural products may hold promise in managing IBD. These natural products have shown the ability to reduce IBD progression by decreasing pro-inflammatory cytokines, inhibiting intestinal inflammation, regulating interleukins, NF κB, JAK STAT signaling, and addressing the imbalance in T helper 17 regulatory T cells. Additionally, these natural products can also lower oxidative stress and lessen the severity of ulcerative colitis. The study demonstrates that the effectiveness of these natural products in reducing intestinal inflammation is closely tied to their ability to decrease levels of pro-inflammatory cytokines like tumor necrosis factor alpha (TNF α), interleukin (IL) 1β, and IL 17. The preclinical data presented in the review highlights the potential for these natural products to be used in the treatment of IBD, with their main actions centered around nuclear factor kappa B (NF κB), the Janus kinase (JAK) signal transducer and activator of transcription (STAT) signaling pathway, regulation of the T helper 17 regulatory T cells balance, and alleviation of oxidative stress.