As a part of intestinal innate immunity, Paneth cells in the base of intestine crypts are main producers of antimicrobial peptides

As a part of intestinal innate immunity, Paneth cells in the base of intestine crypts are main producers of antimicrobial peptides.33 Decreased antimicrobial peptides lead to elevated bacterial colonization and hyperactive adaptive immune response.34 Mucosal epithelial cells under the Benzoylaconitine mucus layer not only directly isolate gut microbiota but also secrete cytokines and chemokines to regulate the mucosal immune system.31 In mucosal epithelium, innate lymphoid cells (ILCs) play an important role in regulating the magnitude of inflammation and maintaining intestinal homeostasis.31 By secreting interleukin (IL)-22, ILCs promote healing during infection and counteract the damaging effect of immune response.35 In the meantime, ILCs also stimulate the production of antimicrobial peptides to kill gram-positive bacteria.36 Peyers patches are the core component of gut-associated lymphoid tissue and are distributed throughout the small intestine.37 Distinguished from peripheral lymph organs, PP harbor some specialized structures.37 Notably, there are no afferent lymphatics in PP. we highlight the role of gut microbiota in cancer immunotherapy including immune checkpoint inhibitor and adoptive cell transfer. for gastric cancer and for biliary cancer.14,15 The carcinogenic role of is related to its genotoxic effect, which further results in chronic inflammation and hyperactive proliferation signaling pathways in mucosal cells.14 Following long-term stimulation, could induce malignant transformation in gastric epithelia and mucosa-associated lymphoid tissues.14 Moreover, it has been verified Goat polyclonal to IgG (H+L) that gut microbiota closely associate with host immunity.16,17 On the one hand, the gut microbiota participates in the development of the host immune system.18 On the other hand, the composition of gut microbiota is modulated by host immunity.19 Accumulating evidence demonstrates that gut microbiota could affect the therapeutic effect of multiple cancer treatments including chemotherapy, radiotherapy, as well as immunotherapy.20-22 The results of in vitro and in vivo studies showed that gut microbiota could regulate the efficacy of chemotherapy by multiple approaches, including (1) Translocation: bacteria cross chemotherapy-induced damaged gut mucosal barrier and enter peripheral lymph nodes; (2) Immunomodulation: gut microbiota promotes chemotherapy-related inflammation; (3) Metabolism and enzymatic degradation: gut microbiota could directly or indirectly modify the structure of pharmaceuticals, which might enhance or abrogate the efficacy of treatment and introduce toxic compounds; (4) Reduced diversity: chemotherapy tends to reduce to the diversity of gut microbiota and leads to the formation of pathogen-dominant gut flora and higher risk of gastrointestinal reactions.20 However, the exact mechanism by which gut microbiota modulates the efficacy of immunotherapy is still unclear. Benefiting from the development of sequencing technology, Benzoylaconitine it is now possible to analyze the composition of the microbiota.23 Commonly, 16S rRNA and metagenomic shotgun sequencing are adopted for taxonomic assignment.24 Taxonomic identification by 16S rRNA is based on the comparison between detection results and known database. Therefore, with 16S rRNA sequencing, it is difficult to identify unknown species.24 Compared with 16S rRNA sequencing, metagenomic shotgun sequencing could directly analyze the whole genomic context, which could be used for taxonomic identification and function analysis.24 Moreover, more and more microbiome studies utilize long-read sequencing that could overcome the limitations of next-generation sequencing such as identifying structural variants, repetitive regions, alleles, and highly homologous genomic regions. Given the vital role of gut Benzoylaconitine microbiota in anticancer therapy, identifying efficacy-related bacteria provide a novel perspective to counteract drug resistance especially for immunotherapy. The Cross-Talk Between Gut Microbiota and the Host Immune System The cross-talk between gut microbiota and immunity is complicated. Host immunity not only sustains tolerance to symbiotic commensals and food antigens but also recognizes opportunistic bacteria and defends against pathogen infection.25 In the meantime, the influence of gut microbiota on the host immune system is multifaceted, from localized immune response to systemic innate or adaptive immunity.25 It was observed that mice that were bred and raised in a sterile environment (germ-free mice) were prone to harbor deficiencies in the development of gut-associated lymphoid tissues especially Peyers patches (PP) and isolated lymphoid follicles.26 Besides, depleting gut microbiota by broad-spectrum antibiotics inhibited murine bone marrow hematopoiesis and decreased the abundance of hematopoietic stem cells or multipotent progenitors.27 Gut Mucosal Immune System The gut mucosal immune system contains organized lymphoid tissues located in the gut mucosal epithelium, lamina propria, and mesentery including PP, isolated lymphoid follicles, and mesenteric lymph node.28-30 Among them, the mucus layer and mucosal epithelium comprise the physical barrier of gut mucosal immunity. 31 It is generally believed that the mucus is mainly produced by goblet cells.32 During mucus secretion, goblet cells in the small intestine can sense and sample luminal content.32 In a manner that has not been well studied, actively secreting goblet cells take up antigenic materials and deliver them to dendritic cells (DCs) in lamina propria.32 Notably, the mucus contains abundant antimicrobial peptides that effectively clear bacterial clones on gut epithelium. As a part of intestinal innate immunity, Paneth cells in the base of intestine crypts are main producers of antimicrobial peptides.33 Decreased antimicrobial peptides lead to elevated bacterial colonization and hyperactive adaptive immune response.34 Mucosal epithelial cells under the mucus layer not only directly isolate gut microbiota but also secrete cytokines and chemokines to.