Ulcerative Colitis: Current and Emerging Treatment Strategies

Kayal, Maia; Shah, Shailja C.

doi:10.3390/jcm9010094

Cited by 74 publications

(42 citation statements)

References 70 publications

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“…Ulcerative colitis is emerging as one of the most healththreatening diseases in the world, but the effective methods for the prediction, prevention and treatment of this disease are still limited (Lissner and Siegmund, 2013;Kayal and Shah, 2019;Oka and Sartor, 2020). Hence, there remains an urgent need for the development and implementation of highly effective and safe complementary and alternative therapies.…”

Section: Discussionmentioning

confidence: 99%

Indigo Naturalis Alleviates Dextran Sulfate Sodium-Induced Colitis in Rats via Altering Gut Microbiota

Sun

Dai

et al. 2020

Front. Microbiol.

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Ulcerative colitis is a gastrointestinal disorder intricately associated with intestinal dysbiosis, but effective treatments are currently limited. Indigo naturalis, a traditional Chinese medicine derived from indigo plants, has been widely used in the treatment of ulcerative colitis. However, the specific mechanisms have not yet been identified. Accordingly, in this study, we evaluated the effects and mechanisms of indigo naturalis on dextran sulfate sodium (DSS)-induced colitis in rats. Our results showed that indigo naturalis potently alleviated DSS-induced colitis in rats, and reversed DSS-induced intestinal dysbiosis using bacterial 16S rRNA amplicon sequencing. The protective effects of indigo naturalis were gut microbiota dependent, as demonstrated by antibiotic treatments and fecal microbiota transplantation. Depletion of the gut microbiota through a combination of antibiotic treatments blocked the anti-inflammatory effect of indigo naturalis on the DSS-induced colitis, and the recipients of the gut microbiota from indigo naturalis-treated rats displayed a significantly attenuated intestinal inflammation, which was actively responsive to therapeutic interventions with indigo naturalis. Notably, supplement with indigo naturalis greatly increased the levels of feces butyrate, which was positively correlated with the relative abundances of Ruminococcus_1 and Butyricicoccus. We further showed that indigo naturalis-dependent attenuation of colitis was associated with elevated expression of short-chain fatty acid-associated receptors GPR41 and GPR43. Collectively, these results suggested that indigo naturalis alleviates DSS-induced colitis in rats through a mechanism of the microbiota-butyrate axis, particularly alterations in Ruminococcus_1 and Butyricicoccus abundances, and targetspecific microbial species may have unique therapeutic promise for ulcerative colitis.

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Section: Discussionmentioning

confidence: 99%

Indigo Naturalis Alleviates Dextran Sulfate Sodium-Induced Colitis in Rats via Altering Gut Microbiota

Sun

Dai

et al. 2020

Front. Microbiol.

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“…The chimeric antibody against TNFα, namely infliximab (IFX), represents the herald of a class of biologic drugs that target specific cytokines in the inflammatory cascade. Subsequently, several new biologic agents were introduced into clinical practice, including the less immunogenic humanized antibody against TNFα (i.e., adalimumab (ADA)), anti-integrin agents (i.e., vedolizumab (VDZ)), and anti-interleukin agents (i.e., ustekinumab (UTK)) [13]. These therapies proved effective at inducing disease remission, improving patient outcomes, and preventing progression to irreversible bowel damage [14].…”

Section: Introductionmentioning

confidence: 99%

On-Treatment Decrease of Serum Interleukin-6 as a Predictor of Clinical Response to Biologic Therapy in Patients with Inflammatory Bowel Diseases

Caviglia

Rosso

Stalla

et al. 2020

JCM

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In patients with inflammatory bowel diseases (IBD) undergoing biologic therapy, biomarkers of treatment response are still scarce. This study aimed to evaluate whether serum zonulin, a biomarker of intestinal permeability; soluble CD163 (sCD163), a macrophage activation marker; and a panel of serum cytokines could predict the response to biologic treatment in patients with IBD. For this purpose, we prospectively enrolled 101 patients with IBD and 19 patients with irritable bowel syndrome (IBS) as a control group; 60 out of 101 patients underwent treatment with biologics. Zonulin, sCD163, and cytokines were measured at the baseline in all patients and after 10 weeks of treatment in the 60 patients who underwent biologic therapy. We observed that zonulin levels were higher in IBD patients with active disease compared to those in remission (p = 0.035), and that sCD163 values were higher in patients with IBD compared to those with IBS (p = 0.042), but no association with therapy response was observed for either biomarker. Conversely, interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor-alpha showed a significant reduction from baseline to week 10 of treatment, particularly in responder patients. By multivariate logistic regression analysis corrected for disease (Crohn’s disease or ulcerative colitis), type of biologic drug (Infliximab, Adalimumab, Vedolizumab, or Ustekinumab) and disease activity, the reduction in IL-6 values was associated with a clinical response at 12 months of biological therapy (odds ratio (OR) = 4.75, 95% confidence interval (CI) 1.25–18.02, p = 0.022). In conclusion, the measurement of serum IL-6 in biologics-treated IBD patients may allow for the prediction of response to treatment at 12 months of therapy and thus may help with tailoring personalized treatment strategies.

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“…The natural course of UC includes periods of remission interspersed with periods of acute exacerbations. The goal of treatment is to achieve disease remission and prevent disease-related complications such as infection, surgery, and neoplasia, as well as preserve patient's quality of life (Kayal & Shah, 2019). Clinical therapies for UC include anti-inflammatory steroids, NSAIDs and TNF-α inhibitors; these are solely used for disease control, and do not represent cures.…”

Section: Discussionmentioning

confidence: 99%

Gabapentin improves colonic inflammatory damage and oxidative stress on acetic acid-induced colitis independent of cannabinoid pathway

Batista¹,

Magalhães²,

Sousa³

et al. 2021

RSD

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Objective: Gabapentin (GBP) possess a systemic anti-inflammatory action confirmed and endocannabinoids system have been effectives in reduces inflammatory disorders on intestinal tract. The aim of this study is evaluate the participation of the endogenous cannabinoids pathway in the anti-inflammatory and antioxidant effects of GBP in acetic acid (AA) induced colitis in mice. Methods: Colitis induction was performed using AA (6%) and mice treated intraperitoneally with GBP or dexamethasone (subcutaneously) at 17 h or 17:30 h after induction of colitis, respectively. After 18 h of colitis induction, the animals were euthanized and colonic sample was taken for evaluation of macroscopic and microscopic lesion, wet weight and biochemical analyzes. Results: The administration of GBP was effective in reduce the macro and microscopic lesions, significant decreasing the colonic wet weight of colitis mice. The drug reduced the concentration myeloperoxidase (MPO), malondialdehyde (MDA) and interleukin 1 (IL-1) and increased the level glutathione (GSH) in colitis mice compared to normal mice. The treatment with endocannabinoids (ECs) receptors antagonists did not alter the GBP effect. Conclusion: Gabapentin was able to reduce inflammatory parameters in acid acetic-induced colitis, but its effect seems to be independent of cannabinoid pathway.

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Ulcerative Colitis: Current and Emerging Treatment Strategies

Cited by 74 publications

References 70 publications

Indigo Naturalis Alleviates Dextran Sulfate Sodium-Induced Colitis in Rats via Altering Gut Microbiota

Indigo Naturalis Alleviates Dextran Sulfate Sodium-Induced Colitis in Rats via Altering Gut Microbiota

On-Treatment Decrease of Serum Interleukin-6 as a Predictor of Clinical Response to Biologic Therapy in Patients with Inflammatory Bowel Diseases

Gabapentin improves colonic inflammatory damage and oxidative stress on acetic acid-induced colitis independent of cannabinoid pathway

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