The aetiology and pathogenesis of inflammatory bowel disease (IBD) remains unclear but involves a complex interplay between genetic risk, environmental exposures, the immune system and the gut microbiota. Nearly two decades ago, the first susceptibility gene for Crohn's disease, NOD2, was identified within the IBD 1 locus. Since then, over 230 genetic risk loci have been associated with IBD and yet NOD2 remains the strongest association to date. As an intracellular innate immune sensor of bacteria, investigations into host–microbe interactions, involving both innate and adaptive immune responses, have become of particular interest in understanding the pathogenesis of IBD. Advancements in sequencing technology have lead to the groundbreaking characterization of the gut microbiota and its role in health and disease. While an altered microbiome has been described for IBD, whether it is a cause or an effect of the intestinal inflammation has yet to be determined. Moreover, the bidirectional relationship between the gut microbiota and the mucosal immune system adds to the multifaceted complexity of intestinal homeostasis. A better understanding of how host genetics, including NOD2, influence immune–microbe interactions and alter susceptibility to IBD is necessary in order to develop therapeutic and preventative treatments. 




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https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/JP275396

The interplay between microbes and the immune response in inflammatory bowel disease.

Increasing antimicrobial resistance, together with the occurrence of side effects of NSAIDs or glucocorticoids represents certain motivation to search for new natural dual antimicrobial and anti-inflammatory drugs We here present selected natural compounds, possessing both antimicrobial and anti-inflammatory activity The review contains also the information about structure–activity relationships with respect to natural or semisynthetic origin of compounds and synergy effects between natural dual inhibitors and commercially available antibiotics Data published from 2000 to 2018 were obtained using databases Google Scholar, Science Direct and Web of Science, and searching keywords such as alkaloids, anti-inflammatory activity, antimicrobial activity, chalcones, coumarins, flavonoids, IC50, lignans, MIC, natural compounds, synergistic effect and terpenoids, alone or in a combination The primary criteria for the selection of appropriate compounds were the MICs and IC50s used for a quantification of effects The natural compounds with activity close to the reference substances or showing MIC up to 32 µg ml−1, and IC50 of anti-inflammatory effect up to 15 µM were considered as promising When available, information about in vivo testing was included Reviewed dual inhibitors can represent modern therapeutic approach, especially when the process of inflammation is followed by a secondary bacterial infection Benefits of dual inhibitors are based on better compliance of patients, decreased number of side effects and extended spectrum of action

Natural compounds with dual antimicrobial and anti-inflammatory effects

Objectives : Auklandia Lappa (ALE) is one of the herbs used frequently to treat abdominal pain and diarrhea and reported anti-inflammatory activity by suppressing proinflammatory cytokines. This study was designed to investigate whether ALE could show protective activities on experimental colitis in...

https://www.jikm.or.kr/upload/pdf/201306/201306_3402_03.pdf

Effects of Auklandia Lappa on Dextran Sulfate Sodium-Induced Murine Colitis

Pathobionts employ unique metabolic adaptation mechanisms to maximize their growth in disease conditions. Adherent–invasive Escherichia coli (AIEC), a pathobiont enriched in the gut mucosa of patients with inflammatory bowel disease (IBD), utilizes diet-derived L-serine to adapt to the inflamed gut. Therefore, the restriction of dietary L-serine starves AIEC and limits its fitness advantage. Here, we find that AIEC can overcome this nutrient limitation by switching the nutrient source from the diet to the host cells in the presence of mucolytic bacteria. During diet-derived L-serine restriction, the mucolytic symbiont Akkermansia muciniphila promotes the encroachment of AIEC to the epithelial niche by degrading the mucus layer. In the epithelial niche, AIEC acquires L-serine from the colonic epithelium and thus proliferates. Our work suggests that the indirect metabolic network between pathobionts and commensal symbionts enables pathobionts to overcome nutritional restriction and thrive in the gut.

/pdf/mucolytic-bacteria-license-pathobionts-to-acquire-host-20hn5tof.pdf

Mucolytic bacteria license pathobionts to acquire host-derived nutrients during dietary nutrient restriction

Objectives: Inflammatory bowel disease (IBD) is chronic inflammatory disorders of the intestines. Due to limitation of conventional treatment including steroids, herbal medicines have emerged as possible therapeutic options for IBD. The purpose of the current study was to investigate the therapeutic and prophylactic effects and mechanisms of Zostera Marina water extract (ZME) on DSS-induced colitis. Methods: Colitis was induced by DSS in Balb/c mice. In pre-treatment setting, ZME was administered 7 days before DSS treatment and in co-treatment setting, ZME was simultaneously administrated with DSS treatment. In both settings, ZME 100, 300 and 1000 mg/kg were orally administered twice a day, respectively. Mice weight and clinical findings were measured daily. Colon length, macroscopic findings and histological damages of colon mucosa were assessed at the end of experiments. The levels of cytokines including TNF-, IFN-, IL-1, IL-6, IL-10 and IL-17 were measured by Biometric Multiplex Cytokine Profiling method. Results: In a dose dependent manner, ZME significantly inhibited the colon shortening, and improved macroscopic score and histological score. However, there were insignificant changes on inhibition of weight loss and improvement of clinical score. There were no significant differences of effects between co-treatment and pre-treatment settings. ZME 300 and 1000 mg/kg groups significantly inhibited IFN-. Only ZME 1000 mg/kg group significantly inhibited TNF-, IL-1 and IL-6. Conclusions: The current results show the possibility of therapeutic use and its prophylactic application of ZME on inflammatory bowel diseases. Future studies for targeted mechanisms of ZME are needed.

/pdf/therapeutic-and-prophylactic-effects-of-zostera-marina-on-1g6a2m6wbw.pdf

春陽温

Papers

Dextran Sulfate Sodium 大腸炎における核塵の発現と意義

春陽 温

Papers

Dextran Sulfate Sodium 大腸炎における核塵の発現と意義

春陽温