The response of patients with bile acid diarrhoea to the farnesoid X receptor agonist obeticholic acid

Walters, Julian R.F.; Johnston, Ian; Nolan, Jonathan; Vassie, Claire; Pruzanski, Mark; Shapiro, D. A.

doi:10.1111/apt.12999

Cited by 146 publications

(124 citation statements)

References 34 publications

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“…Our results also indicate that high lipid levels and excess body weight, along with elevated FGF19 expression, may be associated with the incidence of colon adenoma. Previous studies have suggested that FGF19 expression is stimulated by the nuclear bile acid receptor FXR (farnesoid × receptor), and that hepatic FGF19 synthesis triggers downstream signaling network [38,39]. Several genes involved in the synthesis/transport of fatty acids were reported to be repressed in FGF19 gene knock-in mice and in mice treated with recombinant FGF19 as a form of negative feedback [40][41][42].…”

Section: Discussionmentioning

confidence: 99%

Upregulation of Fibroblast Growth Factor 19 Is Associated with the Initiation of Colorectal Adenoma

Wang

Zhang

et al. 2018

Dig Dis

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Fibroblast growth factor 19 (FGF19) promotes tumor growth in various types of cancer, but its function has not been investigated in the context of colorectal adenoma. Here, we report that FGF19 expression was greater in colorectal adenoma than in normal tissues, as measured by an enzyme-linked immunosorbent assay, quantitative reverse-transcription PCR and immunohistochemistry. FGF19 expression was also elevated in a subset of human colon cancer cell lines. Moreover, FGF receptor 4 (FGFR4), the cognate receptor for FGF19, was upregulated in colorectal adenoma tissues. Lipid levels and body mass index values strongly correlated with FGF19 and FGFR4 levels in patients with colon adenomas. These observations indicate that the FGF19/FGFR4 pathway may be involved in the development of neoplasia, and that FGF19 may be a valuable diagnostic marker for the identification of patients with colorectal adenomas.

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Section: Discussionmentioning

confidence: 99%

Upregulation of Fibroblast Growth Factor 19 Is Associated with the Initiation of Colorectal Adenoma

Wang

Zhang

et al. 2018

Dig Dis

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“…We can hypothesize that BA malabsorption that has been described to occur in MC could lead to a secondary feedback down-regulation of colonic FXR, or that alternatively inflammation in the colon leading to FXR down-regulation could render the epithelial cells more susceptible to the noxious effects of BAs. Even if preliminary, our results open the possibility of studying the use of the new FXR agonist, obeticholic acid [39,40] , in patients with refractory MC, and open avenues for a new line of research in this puzzling cause of intestinal inflammation.…”

mentioning

confidence: 86%

Farnesoid X Receptor Expression in Microscopic Colitis: A Potential Role in Disease Etiopathogenesis

Torres

Palmela

Sena

et al. 2017

GE Port J Gastroenterol

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Introduction: Microscopic colitis (MC) is a chronic inflammatory bowel disease with unclear etiology. Bile acid (BA) malabsorption has been described in MC patients. Farnesoid X receptor (FXR) is the main BA receptor; FXR-mediated mechanisms prevent the noxious effects of BA accumulation, preserving the integrity of the intestinal epithelial barrier and preventing intestinal inflammation. Aim: Our aim was to describe the expression of FXR in patients with MC. Methods: Archival formalin-fixed paraffin-embedded samples from the terminal ileum, right and left colon were obtained from patients with MC and matched controls. Immunohistochemistry was performed and nuclear FXR expression scored in a semi-quantitative way. Results: 169 formalin-fixed paraffin-embedded samples from 35 patients with MC and 31 controls were retrieved. There was a significant reduction of FXR expression in patients with MC versus controls both in the right colon (moderate-strong FXR expression: 21.1 vs. 64.3%; p = 0.003) and left colon (moderate-strong FXR expression: 8.3 vs. 38.7%; p = 0.027). No significant differences in FXR expression were observed in the ileum of patients with MC (moderate-strong FXR expression: 76.9 vs. 90.9%; p = 0.5). We found no difference in FXR expression between the two types of MC. No association between the degree of lymphocyte infiltration or the thickness of collagen band and FXR expression was found. Conclusions: Patients with MC present a significantly lower expression of FXR in the colon. This could render colonic epithelial cells more susceptible to the deleterious effects of BA, contributing to disease pathogenesis and symptoms in MC.

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“…En fase experimental se están desarrollando agonistas de FXR que han mostrado cierta respuesta clínica (53,54). El ácido obeticólico ha sido evaluado en pequeños grupos de pacientes; después de 2 semanas de tratamiento en pacientes con diarrea crónica secundaria a mala-absorción de AB, se redujo la frecuencia de las deposiciones y el índice de diarrea en un 14% y 34%, respectivamente; el tratamiento con ácido obeticólico también documentó reducción de los valores sé-ricos de colesterol y triglicéridos en pacientes tratados con secuestradores de AB (55).…”

Section: Agonistas De Fxrunclassified

Diarrea pos colecistectomía, enfoque diagnóstico y terapéutico

Jaramillo¹,

S²,

Regino³

2017

Rev. Med.

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RESUMENLa colelitiasis es una enfermedad muy prevalente en la población general. El tratamiento de la colelitiasis, cuando se torna sintomática, es fundamentalmente quirúrgico. Una de sus complicaciones es la diarrea pos-colecistectomía que se define como la presencia de 3 o más deposiciones diarreicas por día por más de cuatro semanas en pacientes con el antecedente de colecistectomía, en ausencia de otra causa que explique la sintomatología. Debido a la incidencia reportada en la literatura alrededor del 15%, esta revisión presenta la epidemiologia, fisiopatología, diagnóstico, clasificación y tratamiento de esta patología. Adicionalmente se plantea una nueva clasificación de la patología que se correlacione con la fisiopatología.

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The response of patients with bile acid diarrhoea to the farnesoid X receptor agonist obeticholic acid

Cited by 146 publications

References 34 publications

Upregulation of Fibroblast Growth Factor 19 Is Associated with the Initiation of Colorectal Adenoma

Upregulation of Fibroblast Growth Factor 19 Is Associated with the Initiation of Colorectal Adenoma

Farnesoid X Receptor Expression in Microscopic Colitis: A Potential Role in Disease Etiopathogenesis

Diarrea pos colecistectomía, enfoque diagnóstico y terapéutico

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