A Potential Role for Gut Microbes in Mediating Effects of Omega-3 Fatty Acids in Inflammatory Bowel Diseases: A Comprehensive Review.

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) have been associated with several inflammatory conditions, including inflammatory bowel diseases (IBDs), and found to have an impact on gut microbiota. In fact, some randomized controlled studies suggest benefits to IBD patients, but others do not. Our aim was to review recent evidence on the effects of omega-3 on IBD and establish the contribution of the gut microbiome. Omega-3 mediate anti-inflammatory effects in IBD through various mechanisms, including suppression of NLR family pyrin domain-containing 3 (NLRP3) inflammasome, Toll-like receptor-4 (TLR4), and nucleotide-binding oligomerization domain 2 (NOD2) signaling; this results in the repression of the nuclear factor-kappa B (Nf-kB) pathway and the secretion of pro-inflammatory cytokines. Omega-3 can also affect gut microbiota and revert the bacterial community to patterns associated with healthy status by increasing short-chain fatty acid (SCFA)-producing bacteria and enhancing the mucosal gut barrier, thus promoting homeostasis. The combination of these immunoregulatory effects and anti-inflammation properties with the promotion of a balanced gut microbiome environment could suggest that omega-3 might benefit IBD patients. Considering the microbiota of IBD patients while using omega-3 might predict and improve omega-3 effectiveness. Combining omega-3 with bacteria-altering therapy, such as probiotics and fecal microbiota transplantation, may further enhance its efficacy; however, further studies are required to elucidate mechanisms and potential preventive or treatment roles of omega-3 in IBD.

Appendix and Ulcerative Colitis: a Key to Explaining the Pathogenesis and Directing Novel Therapies?

The vermiform appendix is generally considered a redundant organ, but recent evidence suggests that the appendix could contribute to the pathogenesis of inflammatory bowel diseases, in particular ulcerative colitis (UC), and may even have a therapeutic role; however, mechanisms of the appendix involvement remain unclear. Here, we highlight current evidence on the link between the appendix and UC and consider plausible therapeutic implications. A literature search was conducted using PubMed and PubMed Central from inception to Nov 2021 using the terms "Appendix", "UC", "Appendix & UC," "Appendectomy", and "Peri-appendicular patch," including only articles published in English. Reference lists from the selected studies were manually searched and reviewed to gather additional related reports. Inflammation around the appendix ("peri-appendicular patch") has been frequently observed in UC patients without other cecal involvement, and this inflammation can even precede the onset of UC. Epidemiologic studies propose that appendectomy reduces the risk of developing UC or even the risk of flare after UC is diagnosed, although this remains controversial. We reviewed studies showing altered host-microbe interactions in the appendix in UC, which suggest that the appendix could act as a priming site for disease via alterations in the immune response and changes in microbiota carried distally to the colon. In summary, recent literature suggests a possible role for microbes and immune cells within the appendix; however, the role of the appendix in the pathogenesis of UC remains unclear. Further research could clarify the therapeutic potential related to this organ.

Efficacy and Safety of G2013 as a Novel Immunosuppressive Agent on Differentiation, Maturation and Function of Human Dendritic Cells.

BACKGROUND: The expanse of dendritic cells (DC) differentiation plays an important role in determining immune response. DC-based immunosuppressive drugs have notable side effects in increasing the risk of infectious diseases and cancers. G2013, as a novel anti-inflammatory and immunosuppressive agent, has been tested in experimental model of multiple sclerosis. The aim of this study was to conduct the safety property of G2013 on dendritic cells biology. METHODS: The effect of G2013 on differentiation, maturation, and function of dendritic cells was examined at Tehran University in 2014. To investigate how G2013 affects human dendritic cells (DC) in a defined inflammatory environment, human peripheral blood mononuclear cells (PBMC) were isolated from healthy blood. Monocytes were then purified using anti-CD14 microbeads. Monocytes were treated with G2013 in two different doses (6 and 12 µg/well) along with adding granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 for inducing monocytes to immature DC and adding lipopolysaccharide for running DC maturation. Differentiation, maturation, and function of dendritic cells were examined with flow cytometry and ELISA. RESULTS: G2013 therapy had no significant effect on CD83, CD86 and DR expression, as well as IL-10 and IL-12 cytokine levels and it, has no remarkable side on differentiation, maturation and function of dendritic cells in immature DC and mature DC process in vitro. CONCLUSION: G2013 is a safe agent with no adverse effect on differentiation, maturation, and function of dendritic cells. It may be recommended as a novel immunosuppressive agent with no or little side effect in increasing the risk of infectious diseases and cancers.