**6. Conclusion**

Even though there has been a massive upsurge in the research related to hostmicrobiota interactions as well as the role of genetics, environmental factors, and the immune system in IBD, several facets of IBD pathogenesis remain obscure. This chapter collates the contemporary advancements in host-microbiota investigations which can be pivotal in detecting the hallmarks of IBD leading to upgraded comprehension of its pathogenesis, extension of the diagnostic repertoire and discovery of cutting-edge therapeutic targets for this disease.

EVs have emerged as prominent tools in deciphering the complex host-microbiota interactions in healthy as well as disease states. They not only regulate the gut microbiome communities, but also actively participate in the disharmony between bacteria and their hosts. EVs derived from gut commensal bacteria have been studied to play a crucial role in immunomodulation and regulating gut homeostasis in IBD [22]. The

first proteomic characterization of intestinal EVs from children with new-onset IBD illustrated the presence of host defense proteins in the isolated EV samples, especially the reactive oxidant-producing enzymes responsible for increased oxidative stress in the intestine [26]. Increased oxidative stress triggers microbial defense responses and functional alterations leading to gut microbial dysbiosis and mucosal inflammation [58]. This learning is crucial for the thorough analysis of host–microbiome interactions underlying the development of IBD and the potential use of EVs as diagnostic markers and/or therapeutic agents.

Dysbiosis of microbiota in germ-free mice have been demonstrated to cause abnormal imprinting of the intestinal immune system [29]. It provides a potential link between early life exposures, microbiome and future risk of IBD, highlighting the consequences of the abnormal establishment of early life microbiome during the development of the immune system. Maternal IBD negatively impacts the development of a baby's intestinal ecosystem. Dysbiosis, in pregnant women with IBD or during early infancy can be aimed for promoting the development of a healthy microbiome in the offspring and reducing the potential risk of IBD.

Intestinal resident macrophages are acknowledged as key cellular sensors, integrating signals from the luminal microbiota to regulate intestinal homeostasis. Recent studies affirm their role in promoting anti-inflammatory environment in the healthy gut and switching to a proinflammatory state in response to any alterations in the intestinal microbiota [59]. Follow-up studies should be done to devise tools for identifying patients with compromised resident intestinal macrophages function and evaluating the clinical advantages of targeting the microbiota and immune dysfunctions within this subset of IBD patients. Intestinal macrophage subsets also exhibit peculiar activity in stimulating mucosal IgA responses [47]. This differential activity can be harnessed for designing anti-inflammatory therapies aimed at modulating macrophage function in inflammatory bowel disease.

IBD includes Crohn's disease and ulcerative colitis which are two distinct pathological conditions macroscopically, but often misinterpreted or difficult to distinguish on a deeper extent. There has been evidence of disease-specific statistical shifts in some bacterial species as well as phyla, peculiar to each subtype of IBD [56]. Single-cell analysis with CyTOF on IBD and non-IBD colonic mucosa and blood to identify disease-specific immune signatures revealed the abundance of HLA-DR<sup>+</sup> CD38<sup>+</sup> T cells in both active Crohn's disease (CDa) and ulcerative colitis (UCa) mucosa [57]. CD38 has been involved in colitis in mice [60] whereas CD38<sup>+</sup> effector T cells in pediatric IBD [61], suggesting that CD38 could be targeted for IBD therapy. Various disease-specific mucosal signatures associated with differential cytokine expression were also reported. IL1B signatures particular to CD involved HLA-DR<sup>+</sup> CD38<sup>+</sup> T cells, naïve B cells, and DCs. IL1B<sup>+</sup> macrophages/ monocytes were augmented in both CDa and Uca mucosa, along with a specific expansion of IL1B+ monocytes to only peripheral CDa [57, 62]. Thus, exploiting IL1B can be a promising therapeutic strategy for subsets of Crohn's disease. These extrusive microbial and immunological signatures of IBD can also be of high biological and diagnostic potential. To sum up, the above-discussed studies have a robust potential of heralding state-of-art diagnostic as well as therapeutic avenues in the field of inflammatory bowel disease. Further translational work based upon these findings can lead to the upgradation of our insight and methodology towards gut disorders as critical as IBD with a prospect of personalized therapies soon.

*Host-Microbiota Interplay in IBD: The Emerging Role of Extracellular Vesicles, Perinatal… DOI: http://dx.doi.org/10.5772/intechopen.104696*
