Oral Vancomycin Induces and Maintains Remission of Ulcerative Colitis in the Subset of Patients With Associated Primary Sclerosing Cholangitis

Dao, Alexander; Abidian, Mohamed Modar; LeStrange, Aimee; Mattar, Mark; Rangnekar, Amol S.; Charabaty, Aline

doi:10.1093/ibd/izz027

Cited by 23 publications

(18 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Vancomycin, an antibiotic that specifically targets Gram-positive bacteria [many of which are involved in dehydoxylation of primary bile acids into secondary bile acids] has been shown to induce remission of colitis in patients with PSC-IBD. 35 Furthermore, amine oxidase-expressing bacteria, Sphingomonas sp., were found to be upregulated in PSC-IBD compared with UC. This enzyme is associated with aberrant homing of gut lymphocytes to the liver, a proposed mechanism underlying the PSC-IBD gut-liver inflammatory axis.…”

Section: Discussionmentioning

confidence: 99%

A Pilot Integrative Analysis of Colonic Gene Expression, Gut Microbiota, and Immune Infiltration in Primary Sclerosing Cholangitis-Inflammatory Bowel Disease: Association of Disease With Bile Acid Pathways

Quraishi

Acharjee

Beggs

et al. 2020

Journal of Crohn's and Colitis

View full text Add to dashboard Cite

Background Although a majority of patients with PSC have colitis [PSC-IBD; primary sclerosing cholangitis-inflammatory bowel disease], this is phenotypically different from ulcerative colitis [UC]. We sought to define further the pathophysiological differences between PSC-IBD and UC, by applying a comparative and integrative approach to colonic gene expression, gut microbiota and immune infiltration data. Methods Colonic biopsies were collected from patients with PSC-IBD [n = 10], UC [n = 10], and healthy controls [HC; n = 10]. Shotgun RNA-sequencing for differentially expressed colonic mucosal genes [DEGs], 16S rRNA analysis for microbial profiling, and immunophenotyping were performed followed by multi-omic integration. Results The colonic transcriptome differed significantly between groups [p = 0.01]. Colonic transcriptomes from HC were different from both UC [1343 DEGs] and PSC-IBD [4312 DEGs]. Of these genes, only 939 had shared differential gene expression in both UC and PSC-IBD compared with HC. Imputed pathways were predominantly associated with upregulation of immune response and microbial defense in both disease cohorts compared with HC. There were 1692 DEGs between PSC-IBD and UC. Bile acid signalling pathways were upregulated in PSC-IBD compared with UC [p = 0.02]. Microbiota profiles were different between the three groups [p = 0.01]; with inferred function in PSC-IBD also being consistent with dysregulation of bile acid metabolism. Th17 cells and IL17-producing CD4 cells were increased in both PSC-IBD and UC when compared with HC [p < 0.05]. Multi-omic integration revealed networks involved in bile acid homeostasis and cancer regulation in PSC-IBD. Conclusions Colonic transcriptomic and microbiota analysis in PSC-IBD point toward dysregulation of colonic bile acid homeostasis compared with UC. This highlights important mechanisms and suggests the possibility of novel approaches in treating PSC-IBD.

show abstract

Section: Discussionmentioning

confidence: 99%

A Pilot Integrative Analysis of Colonic Gene Expression, Gut Microbiota, and Immune Infiltration in Primary Sclerosing Cholangitis-Inflammatory Bowel Disease: Association of Disease With Bile Acid Pathways

Quraishi

Acharjee

Beggs

et al. 2020

Journal of Crohn's and Colitis

View full text Add to dashboard Cite

show abstract

“…In this review, vancomycin seemed to be the most effective antibiotic with regard to clinical improvement and adverse effects. Most recently, a small case series by Dao A et al (79) found that oral…”

Section: Treatment Targeting the Microbiomementioning

confidence: 99%

Targeting the Gut Microbiome as a Treatment for Primary Sclerosing Cholangitis: A Conceptional Framework

et al. 2020

View full text Add to dashboard Cite

Primary sclerosing cholangitis (PSC) is a rare, immune-mediated, chronic cholestatic liver disease associated with a unique phenotype of inflammatory bowel disease that frequently manifests as pancolitis with right-sided predominance. Available data suggest a bidirectional interplay of the gut-liver axis with critical roles for the gastrointestinal microbiome and circulating bile acids (BAs) in the pathophysiology of PSC. BAs shape the gut microbiome, whereas gut microbes have the potential to alter BAs, and there are emerging data that alterations of BAs and the microbiome are not simply a consequence but the cause of PSC. Clustering of PSC in families may suggest that PSC occurs in genetically susceptible individuals. After exposure to an environmental trigger (e.g., microbial byproducts or BAs), an aberrant or exaggerated cholangiocyte-induced immune cascade occurs, ultimately leading to bile duct damage and progressive fibrosis. The pathophysiology can be conceptualized as a triad of (1) gut dysbiosis, (2) altered BA metabolism, and (3) immune-mediated biliary injury. Immune activation seems to be central to the disease process, but immunosuppression does not improve clinical outcomes or alter the natural history of PSC. Currently, orthoptic liver transplantation is the only established life-saving treatment, whereas antimicrobial therapy or fecal transplantation is an emerging therapeutic option for PSC. The beneficial effects of these microbiome-based therapies are likely mediated by a shift of the gut microbiome with favorable effects on BA metabolism. In the future, personalized approaches will allow to better target the interdependence between microbiome, immune function, and BA metabolism and potentially cure patients with PSC.

show abstract

“…In our recently published systematic review and meta-analysis [4], we found in adult PSC patients with or without an associated IBD, short-term treatment with antimicrobial therapy, in particular with oral vancomycin (OV), was associated with significant improvement in cholestatic liver enzymes and PSC Mayo risk score (MRS). More recently, Dao et al [5] found that OV was effective for the induction and maintenance of remission of UC in adults with UC-PSC, including PSC patients having undergone orthoptic liver transplantation (OLT). We describe here our experience in a cohort of wellcharacterized adult PSC patients (both pre-and post-OLT), with an associated IBD, who were treated with OV therapy for management of colitis, specifically having failed to respond to conventional medical therapy for management of IBD.…”

Section: Introductionmentioning

confidence: 99%

How frequent are vancomycin-resistant enterococci in patients with primary sclerosing cholangitis and ulcerative colitis treated with oral vancomycin?

Shah

Pakneeshan

Jones

et al. 2022

Indian J Gastroenterol

View full text Add to dashboard Cite

In patients with primary sclerosing cholangitis (PSC), antimicrobial therapy with oral vancomycin (OV) is increasingly used to prevent progression of the liver disease and control concomitant ulcerative colitis (UC); however, there are concerns regarding the risk of development of vancomycin-resistant enterococci (VRE). Thus, we aimed to determine the incidence of VRE in PSC-UC patients. We conducted a retrospective study of PSC-UC patients, treated with OV at the Department of Gastroenterology at the Princess Alexandra Hospital. VRE testing was performed utilizing rectal swabs. We included 7 PSC-UC patients (age 22–53 years, 2 females) treated with OV with daily dose ranging from 250 to 1500 mg. All patients were treated for at least 6 months with OV (range 9–31 months, mean 32.1 months). All patients achieved complete clinical remission of the UC, with mean reduction of fecal calprotectin by 634 μg/mg (87.3%), mean reduction in the C-reactive protein by 21.9 mg/L (74.2%), and mean reduction in the total Mayo score by 9.3 (93.3%). With regard to the liver parameters, mean improvement in alkaline phosphatase enzyme and total bilirubin was −48.7 U/L (−19.7%) and −2.7 mg/dL (−19.6%), respectively. No patient treated with OV developed VRE or reported any adverse events. This cohort study including PSC-UC patients did not provide evidence for development of VRE, while treatment with vancomycin was associated with clinical and endoscopic remission of the UC. Larger, prospective trials are required to define the efficacy and safety of antimicrobial therapy in PSC-UC, while the risk of VRE appears small.

show abstract

Oral Vancomycin Induces and Maintains Remission of Ulcerative Colitis in the Subset of Patients With Associated Primary Sclerosing Cholangitis

Cited by 23 publications

References 3 publications

A Pilot Integrative Analysis of Colonic Gene Expression, Gut Microbiota, and Immune Infiltration in Primary Sclerosing Cholangitis-Inflammatory Bowel Disease: Association of Disease With Bile Acid Pathways

A Pilot Integrative Analysis of Colonic Gene Expression, Gut Microbiota, and Immune Infiltration in Primary Sclerosing Cholangitis-Inflammatory Bowel Disease: Association of Disease With Bile Acid Pathways

Targeting the Gut Microbiome as a Treatment for Primary Sclerosing Cholangitis: A Conceptional Framework

How frequent are vancomycin-resistant enterococci in patients with primary sclerosing cholangitis and ulcerative colitis treated with oral vancomycin?

Contact Info

Product

Resources

About