Background: Inflammatory bowel disease (IBD) is a significant health problem with an increasing financial burden worldwide. Although various treatment strategies have been used, the results were not satisfactory. More and more researches have proved that the application of phosphatidylcholine (PC) may become an alternative therapy for IBD. Objective: This review aims to provide an overview of the possible mechanisms of PC and promote the potential application of PC for IBD therapy further. Methods: A comprehensive literature search was performed in PubMed with the following keywords: ‘phosphatidylcholine’, ‘inflammatory bowel disease’, ‘Crohn's disease’, ‘inflammation’, ‘ulcerative colitis’, ‘therapy’, ‘nanomedicines’, ‘PKCζ’, ‘lysophosphatidylcholine’, ‘microbiota’ and ‘drug carrier’. The logical operators “AND” and “OR” were applied to combine different sets of the search results. Results: Studies suggested that PC displays a significant effect in the treatment of IBD by modulating gut barrier function, remodeling gut microbiota structure, regulating polarization of macrophages, and reducing the inflammatory response. PC has also been exploited as a drug carrier for anticancer or anti-inflammation agents in multiple forms, which implies that PC has immense potential for IBD therapy. Conclusion: PC has shown promising potential as a new therapeutic agent or a drug carrier, with a novel, stable, prolonged mechanism of action in treating IBD. However, more high-quality basic and clinical studies are needed to confirm this.
•MUSE-IVIM can yield high-quality images.•MUSE-IVIM and DCE-MRI can quantify the microcirculatory changes.•MUSE-IVIM and DCE-MRI can stage CD lesions activity. Rationale and ObjectivesTo investigate if the combination of multishot diffusion imaging-based multiplexed sensitivity encoding intravoxel incoherent motion (MUSE-IVIM) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is feasible for staging Crohn's disease (CD) activity.Materials and MethodsA total of 65 CD patients were enrolled and analyzed in this retrospective study. The simplified endoscopic score for Crohn's disease (SES-CD) and magnetic resonance index of activity (MaRIA) were used as the reference. The MUSE-IVIM and DCE-MRI data were acquired at 3.0-T MRI scanner and processed by two radiologists. Three MUSE-IVIM parameters: fast apparent diffusion coefficient (ADCfast), slow apparent diffusion coefficient (ADCslow), and the fractional perfusion (Fraction of ADCfast), as well as four DCE-MRI parameters: volume transfer constant (Ktrans), rate constant (Kep), extravascular extracellular volume fraction (Ve), and plasma volume fraction (Vp) were generated. Intraclass correlation coefficient (ICC), non-parametric test (Kruskal–Wallis H and Mann–Whitney U), logistic regression, receiver operating characteristic analysis, Delong test, and Spearman's correlation test were performed.ResultsAccording to SES-CD, 116 ileocolonic segments with CD lesions were identified as: inactive, mild, and moderate to severe. With multivariable logistic regression analysis, ADCfast (p < 0.001), Fraction of ADCfast (p = 0.005), Ktrans (p < 0.001) and Kep (p = 0.003) were identified as significant factors for differentiating among the three groups. Binary logistic analyses identified ADCfast (p = 0.001), Ktrans (p = 0.014), and Kep (p = 0.029) as independent predictors for the active status. The combination of ADCfast, Ktrans, and K ep performed better than MaRIA score (p = 0.028), for differentiating inactive and active status. MaRIA score was positively correlated with ADCfast (p < 0.001), Ktrans (p < 0.001), Kep (p < 0.001), and Ve (p = 0.001), however, negatively correlated with Fraction of ADCfast (p < 0.001).ConclusionThe combination of MUSE-IVIM and DCE-MRI has been demonstrated to accurately stage inflammatory activity in CD. To investigate if the combination of multishot diffusion imaging-based multiplexed sensitivity encoding intravoxel incoherent motion (MUSE-IVIM) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is feasible for staging Crohn's disease (CD) activity. A total of 65 CD patients were enrolled and analyzed in this retrospective study. The simplified endoscopic score for Crohn's disease (SES-CD) and magnetic resonance index of activity (MaRIA) were used as the reference. The MUSE-IVIM and DCE-MRI data were acquired at 3.0-T MRI scanner and processed by two radiologists. Three MUSE-IVIM parameters: fast apparent diffusion coefficient (ADCfast), slow apparent diffusion coefficient (ADCslow), and the fractional perfusion (Fraction of ADCfast), as well as four DCE-MRI parameters: volume transfer constant (Ktrans), rate constant (Kep), extravascular extracellular volume fraction (Ve), and plasma volume fraction (Vp) were generated. Intraclass correlation coefficient (ICC), non-parametric test (Kruskal–Wallis H and Mann–Whitney U), logistic regression, receiver operating characteristic analysis, Delong test, and Spearman's correlation test were performed. According to SES-CD, 116 ileocolonic segments with CD lesions were identified as: inactive, mild, and moderate to severe. With multivariable logistic regression analysis, ADCfast (p < 0.001), Fraction of ADCfast (p = 0.005), Ktrans (p < 0.001) and Kep (p = 0.003) were identified as significant factors for differentiating among the three groups. Binary logistic analyses identified ADCfast (p = 0.001), Ktrans (p = 0.014), and Kep (p = 0.029) as independent predictors for the active status. The combination of ADCfast, Ktrans, and K ep performed better than MaRIA score (p = 0.028), for differentiating inactive and active status. MaRIA score was positively correlated with ADCfast (p < 0.001), Ktrans (p < 0.001), Kep (p < 0.001), and Ve (p = 0.001), however, negatively correlated with Fraction of ADCfast (p < 0.001). The combination of MUSE-IVIM and DCE-MRI has been demonstrated to accurately stage inflammatory activity in CD.
The pathogenic mechanisms underlying distal symmetric polyneuropathy (DSPN), a common neuropathy in patients with diabetes mellitus (DM), are not fully understood. Here, we discover that the gut microbiota from patients with DSPN can induce a phenotype exhibiting more severe peripheral neuropathy in db/db mice. In a randomized, double-blind, and placebo-controlled trial (ChiCTR1800017257), compared to 10 patients who received placebo, DSPN was significantly alleviated in the 22 patients who received fecal microbiota transplants from healthy donors, independent of glycemic control. The gut bacterial genomes that correlated with the Toronto Clinical Scoring System (TCSS) score were organized in two competing guilds. Increased guild 1, which had higher capacity in butyrate production, and decreased guild 2, which harbored more genes in synthetic pathway of endotoxin, were associated with improved gut barrier integrity and decreased proinflammatory cytokine levels. Moreover, matched enterotype between transplants and recipients showed better therapeutic efficacy with more enriched guild 1 and suppressed guild 2. Thus, changes in these two competing guilds may play a causative role in DSPN and have the potential for therapeutic targeting.
Objective
To evaluate the methodology, safety and clinical applications of colonic transendoscopic enteral tubing (TET) as a new method of fecal microbiota transplantation (FMT) and colonic administration.
Methods
This prospective study included patients who underwent colonic TET for FMT and(or) colonic administration in the Second Affiliated Hospital of Nanjing Medical University from October 2014 to December 2018. The TET procedure time, success rate, retention time of TET tube, factors influencing TET tube retention, adverse events and satisfaction degree were evaluated.
Results
A total of 257 patients underwent TET, among whom 130 patients (50.6%) for microbiota tronsplantation, 8 patients (3.1%) for colon-drip medication, 118 patients (45.9%) for FMT and colon-drip medication, and 1 patient (0.4%) without treatment after TET. The TET procedure time was 10.0±2.8 min. The number of endoscopic clips used was 3.5±1.0. The success rate of the TET procedure was 100.0% (257/257). The retention time of TET tube for 160 patients maintaining the tube for treatment was 9.3±3.8 days. Multivariate analysis indicated that endoscopic clip type (P=0.001) was an independent influencing factor for the retention time of the tube. A total of 9 patients (3.5%) reported adverse events of mild anus discomfort, 4 patients (1.6%) of mobile inconvenience, 3 (1.2%) of anal pain, 2 (0.8%) of mild abdominal pain, 2 (0.8%) of mild bloating, and 1 (0.4%) of mild anal bleeding. No severe adverse events were observed in this study. The total satisfaction degree on colonic TET was 97.3% (250/257) in all patients.
Conclusion
The colonic TET, a safe and easy-operating endoscopic interventional technology with a high degree of patients satisfaction, can be used for colonic delivering of FMT and medications for various diseases.
Key words:
Colonoscopy; Fecal microbiota transplantation; Enema; Transendoscopic enteral tubing
Abstract The exposure to either medical sources or accidental radiation can cause varying degrees of radiation injury (RI). RI is a common disease involving multiple human body parts and organs, yet effective treatments are currently limited. Accumulating evidence suggests gut microbiota are closely associated with the development and prevention of various RI. This article summarizes 10 common types of RI and their possible mechanisms. It also highlights the changes and potential microbiota-based treatments for RI, including probiotics, metabolites, and microbiota transplantation. Additionally, a 5P-Framework is proposed to provide a comprehensive strategy for managing RI.
To the Editor: Long-term use of antifungals can disrupt the balance of fungal community, making the fungal infection treatments more difficulty and aggravating colitis in patients. The exploration of fecal microbiota transplantation (FMT) in reducing Candida to contain pro-inflammatory immunity induced by gut mycobiota has gained a new appreciation.[1] The new methodology of FMT was recently coined as washed microbiota transplantation (WMT) based on the automatic purification system and washing process, released by the consensus statement from the Fecal Microbiota-standardization Study Group in 2019.[2,3] Here, we report a male patient with recurrent fungal infection who was successfully cured by serial WMTs. A 31-year-old male suffered from recurrent diarrhea for 20 years. He was diagnosed with ulcerative colitis (UC) and psoriasis in 2007. He had the medication history of continuous 5-aminosalicylic acid, a large dose of corticosteroid and anti-tumor necrosis factor (TNF) antibody, but showed no sustained benefits. He finally developed corticosteroid-dependence and secondary loss of response to anti-TNF therapy. He had been using cyclosporine since March 2018 to treat the aggravation of pustular psoriasis and UC, which momently improved the skin lesions and diarrhea. Unfortunately, he then suffered diarrhea 10 to 15 times per day since July 2018. The stool was tested positive for Glucan and Galactomannan tests; thus, oral itraconazole was prescribed. However, his intricate fungal infection repeatedly recurred because of his immunocompromised status. He even developed septic shock, with the detection of Candida glabrata infection in blood and fecal fungal culture. He gradually lost response to the antifungal treatments and had severe drug-induced liver injury after the usage of 5-month itraconazole (intravenously, and then orally), 6-month fluconazole, and 1-month voriconazole. He was transferred from the previous hospital to our hospital because of the maintained invasive fungal infection and refractory UC. After admission, the laboratory results showed: elevated white blood cell count, 16.5 × 109/L; the percent of neutrophilic granulocyte, 89.5%; C-reactive protein (CRP), 20.7 mg/L; and erythrocyte sedimentation rate (ESR), 22 mm/h; significantly reduced plasma cortisol (<3 μg/mL) at different points in time; Clostridium difficile test (–); hypothyroidism; anti-thyroid antibody (+); stool bacteria culture (–); and stool fungus culture of C. glabrata (+). Colonoscopy indicated marked erythema, friability, spontaneous bleeding, and extensive ulcers of the whole colon. Plain computed tomography scan confirmed bilateral femoral head necrosis. The patient was diagnosed as UC (E3, severe activity, Mayo score = 11), C. glabrata infection, adrenocortical insufficiency, osteoporosis, femoral head necrosis, psoriasis, Hashimoto thyroiditis, and moderate malnutrition. The ethics of WMT for refractory UC was approved by the Institutional Review Board ([2012] KY No. 015). The patient signed the informed consent of WMT. The five-unit dose of washing microbiota suspension according to WMT protocol was delivered via nasojejunal tube,[2] which was also used as the enteral nutrition way for him. The donor from Chinese fmtBank was screened strictly according to previously reported criteria.[4] The levels of inflammatory markers rapidly decreased within one week and repeated fecal fungal culture results were negative. However, five times of WMTs did not significantly reduce the stool frequency. Cyclosporine was then reintroduced again as the step-up FMT strategy, which refers to the combination of FMTs followed by immunosuppressants.[5] The stool frequency decreased to twice per day 2 weeks later. Biochemical examination, blood routine examination, CRP, and ESR monitoring maintained normal. He insisted on entire enteral nutrition, oral cyclosporine, and thalidomide after discharged. The fecal fungus culture remained negative 3 and 6 months after the first WMT. The life quality of this patient showed significant improvement during the 6-month follow-up. The comprehensive conditions of this case indicated the necessity of individualized treatments for the patient. Corticosteroid is no longer suitable for him because of the limited efficacy and severe complications. The fast-acting cyclosporine can be used as the switch treatments for patients with severe refractory UC, which was discontinued due to uncontrolled fungal infection for this patient. Multiple WMTs eliminated the contradiction between recurrent fungal infection and immunosuppressive agent usage. Therefore, we reintroduced cyclosporine, for the consideration of this medication alleviated his diarrhea previously. Most of the clinical remission of inflammatory bowel disease (IBD) after FMT has been achieved in combination with immunosuppressive agents, defined as step-up FMT strategy.[5] This step-up FMT strategy for treating refractory IBD has gained increasing cognition.[6] Meanwhile, thalidomide can be employed as a treatment option in severe IBD cases by inducing mucosal and histological healing, even in patients with resistance or intolerance to steroids or other anti-TNF agents.[7] Thalidomide has additional effects, including improving nutritional status, decreasing stool frequency, and maintaining clinical remission in IBD patients,[7] which need 8 to 12 weeks to take effect. It is necessary to take oral cyclosporine until thalidomide takes effect. The follow-up confirmed that individualized treatment is effective in improving his symptoms and quality of life. The exploration of gut mycobiota and its correlation with FMT is still in its early stage. The current findings indicated that the inflammatory markers of the patients rapidly decreased after WMT within one week and the repeated fecal fungal cultures were negative during hospitalization and follow-up. This is consistent with the research by Leonardi et al[1], showing a positive outcome of FMT on intestinal inflammation after the reduction of intestinal Candida colonization. Several studies supported the effectiveness of FMT plus traditional treatments in inducing clinical improvement or remission for refractory UC when the sole FMT could not rescue the disease.[4,8] Therefore, step-up FMT strategy might successfully contribute to achieving and maintaining clinical remission in this case. In conclusion, the multiple WMTs plus cyclosporine might induce clinical improvement in the refractory UC. More attention should be paid to gut mycobiota and the potential role of FMT in recurrent fungal infection treatment in clinical practice. Declaration of patient consent The authors certify that they have obtained the patient consent form. In the consent form, the patient has given his consent for his clinical information to be reported in the journal. The patient understands that his name and initial will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed. Acknowledgements The authors thank China Microbiota Transplantation System for the data about the WMT delivering and evaluation on efficacy and safety. The authors appreciate the kindly help from Cicilia Marcella for professionally English editing. Funding This work was supported by a grant from the National Natural Science Foundation of China (No. 81873548). Conflicts of interest Fa-Ming Zhang conceived the concept of GenFMTer, transendoscopic enteral tubing, and related devices. Other authors declare that they have no competing interests.
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